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The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis

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Abstract

The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a “classification tree” schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91–94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

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... The R-R interval 50 The R-R interval 51 Table 3. 3 The results of immediate heart rate response to standing Table 3. 4 The results of the rise in diastolic blood pressure in response to sustained handgrip 56 Table 3. 5 The results of the fall in systolic blood pressure in response to standing 59 Figure 3. 5 The results of the fall in systolic blood pressure in response to standing 60 Table 3. 6 The results of the heart rate response to the Valsalva manoeuvre ...
... The R-R interval 50 The R-R interval 51 Table 3. 3 The results of immediate heart rate response to standing Table 3. 4 The results of the rise in diastolic blood pressure in response to sustained handgrip 56 Table 3. 5 The results of the fall in systolic blood pressure in response to standing 59 Figure 3. 5 The results of the fall in systolic blood pressure in response to standing 60 Table 3. 6 The results of the heart rate response to the Valsalva manoeuvre ...
... Diagnostic criteria may provide helpful information in individual cases. They may not be definitive since the diagnosis may only become apparent with time (Arnett et al. 1988). Other patterns of presentation include an abrupt onset of polyarthritis affecting a number of joints. ...
Thesis
p>Neurological manifestations are seen relatively frequently in patients with rheumatoid arthritis. The occurrence of a peripheral neuropathy is well recognised. Since the 1960s there has been a growing interest in the role of the autonomic nervous system in rheumatoid arthritis. There is conflicting evidence to support this view. The aim of this study was to investigate whether autonomic impairment occurs in rheumatoid arthritis, and if so, whether this is related to age, disease duration or rheumatoid factor status. The influence of disease activity was also investigated. Clinical assessment of autonomic function was carried out using the battery of cardiovascular reflex tests as described by Ewing and Clarke, 1982. The use of these tests is established in clinical practice. Cardiovascular reflexes were measured in 62 rheumatoid arthritis outpatients aged between 38-84 years old (mean age 63.2yrs) and 41 healthy controls aged between 22-82 years old (mean age 48.0yrs) of either sex. None of these subjects had overt cardiovascular disease, other co-pathology known to interfere with autonomic function (such as diabetes), or were taking medication known to interfere with heart rate or blood pressure. The results demonstrated significant differences between the rheumatoid and control group in heart rate responses to the Valsalva manoeuvre (p=0.03), to deep breathing (p=0.01), to standing (p=0.001) and in the rise in the diastolic pressure in response to sustained handgrip (p<0.001). These differences indicate autonomic impairment in the rheumatoid patients, which was not clinically apparent with a fall in systolic blood pressure. Significant differences were also demonstrated in the heart rate responses to the Valsalva manoeuvre between the control group and the rheumatoid factor positive patients (p=0.02), those who had had the disease for longer than 10 years (p=0.01) and in the older subjects (p=0.02). In general this trend is observed when each of the subgroups was compared against controls for the other cardiovascular autonomic reflexes. The exception being age group where no consistent pattern emerged. There was no difference observed in the cardiovascular reflexes when patients with or without peripheral neuropathy were compared with the controls. Furthermore there was no correlation with disease activity. In conclusion, the results indicate that there is a tendency to impaired autonomic function as assessed by the cardiovascular reflexes. This exists on a subclinical level.</p
... Rheumatologists made a pSS diagnosis according to American-European Consensus Group (AECG) classification criteria [24]. Rheumatologists made an RA diagnosis according to 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria [25] or the 1987 ACR classification criteria [26]. Patients with RA-sSS had fulfilled the 2010 ACR/EULAR classification criteria [25] or 1987 ACR classification criteria [26], and sSS was diagnosed by AECG SS classification criteria [24]. ...
... Rheumatologists made an RA diagnosis according to 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria [25] or the 1987 ACR classification criteria [26]. Patients with RA-sSS had fulfilled the 2010 ACR/EULAR classification criteria [25] or 1987 ACR classification criteria [26], and sSS was diagnosed by AECG SS classification criteria [24]. In the discovery steps, novel MDA-modified peptide adducts were identified through agarose-bound concanavalin (Con) A beads (Vector Laboratories, Burlingame, CA, USA), one-dimensional sodium dodecylsulfate polyacrylamide gel electrophoresis (1D SDS-PAGE), in-gel digestion, nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS), and PEAKS 7 software (Bioinformatics Solutions, Waterloo, Canada) and pooled Con A-captured serum protein samples were randomly chosen from nine age-matched HCs and nine patients with pSS. ...
Article
Background Sjogren’s syndrome (SS) is a systemic autoimmune disease featured with a dry mouth and dry eyes. Several autoantibodies, including anti-SSA, anti-SSB, antinuclear antibodies can be detected in patients with SS. Oxidation-specific epitopes (OSEs) can be formed from malondialdehyde (MDA)-modified protein adducts and trigger chronic inflammation. In this study, our purposes were used serum levels of anti-MDA-modified peptide adducts autoantibodies to evaluate predictive performance by machine learning algorithms in primary Sjögren's syndrome (pSS) and assess the association between pSS and healthy controls. Methods Three novel MDA-modified peptide adducts, including immunoglobulin (Ig) gamma heavy chain 1 (IGHG1)102–131, complement factor H (CFAH)1045–1062, and Ig heavy constant alpha 1 (IGHA1)307–327 were identified and validated. Serum levels of protein, MDA-modified protein adducts, MDA, and autoantibodies recognizing unmodified peptides and MDA-modified peptide adducts were measured. Statistically significance in correlations and odds ratios (ORs) were estimated. Results The random forest classifier utilized autoantibodies combination composed of IgM anti-IGHG1¹⁰²⁻¹³¹, IgM anti-IGHG1¹⁰²⁻¹³¹ MDA and IgM anti-IGHA1³⁰⁷⁻³²⁷ achieved predictive performance as an accuracy of 88.0%, a sensitivity of 93.7%, and a specificity of 84.4% which may be as potential diagnostic biomarkers to differentiate patients with pSS from rheumatoid arthritis (RA), and secondary SS in RA and HCs. Conclusions Our findings imply that low levels of IgA anti-IGHG1¹⁰²⁻¹³¹ MDA (OR = 2.646), IgA anti-IGHG1¹⁰²⁻¹³¹ (OR = 2.408), IgA anti-CFAH¹⁰⁴⁵⁻¹⁰⁶² (OR = 2.571), and IgA anti-IGHA1³⁰⁷⁻³²⁷ (OR = 2.905) may denote developing risks of pSS, respectively.
... PMR patients fulfilled the 2012 Provisional Classification Criteria for Polymyalgia Rheumatica, a European League against Rheumatism/American College of Rheumatology collaborative initiative (32). RA patients fulfilled the 1987 or 2010 American College of Rheumatology classification criteria (33,34). Infection was diagnosed based on clinical symptoms, microbiological or radiographic methods, and good response to antibiotics. ...
... Generation and Selection of mAbs mAbs against mCRP were generated and selected as previously described (30). Briefly, mCRP were generated from commercially available human pCRP (human pleural fluid, Lee BioSolutions, Maryland Heights, MO, USA) as described previously (34). BALB/c mice were injected intraperitoneally with approximately 50 mg of mCRP. ...
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BackgroundC-reactive protein (CRP) is a dynamic protein that undergoes conformational changes between circulating native pentameric CRP (pCRP), pentameric symmetrical forms (pCRP*) and monomeric (or modified) CRP (mCRP) forms. mCRP exhibits strong pro-inflammatory activity and activates platelets, leukocytes, and endothelial cells. Abundant deposition of mCRP in inflamed tissues plays a role in several disease conditions, such as ischemia/reperfusion injury, Alzheimer’s disease, and cardiovascular disease. Although pCRP is typically quantified rather than mCRP for clinical purposes, mCRP may be a more appropriate disease marker of inflammatory diseases. Therefore, simple methods for quantifying mCRP are needed.Methods We developed a specific enzyme-linked immunosorbent assay (ELISA) to measure plasma levels of mCRP. Plasma mCRP concentration was measured in patients with adult-onset Still’s disease (AOSD) (n=20), polymyalgia rheumatica (PMR) (n=20), rheumatoid arthritis (RA) (n=30), infection (n=50), and in control subjects (n=30) using the developed ELISA.ResultsWe demonstrated that mCRP is elevated in some inflammatory autoimmune diseases, particularly AOSD. The mCRP concentration was also significantly higher among AOSD patients than RA, PMR patients and controls (477 ng/ml, 77 ng/ml, 186 ng/ml, and 1.2 ng/ml, respectively). Also, the mCRP (×1,000)/pCRP ratio was significantly higher among AOSD patients than RA, PMR, and infection patients (3.5, 0.6, 1,6, and 2.0, respectively).Conclusion The plasma mCRP levels are elevated in some autoimmune diseases, particularly AOSD. The plasma mCRP levels may therefore be a potentially useful biomarker for AOSD.
... Patients were recruited in 54 centers participating in the German nationwide "Sono Remission Plus" project between 2006 and 2010 [19,27]-a prospective, observational study on patients with RA classified according to the American College of Rheumatology (ACR) criteria of 1987 [31]. The study was approved by the ethical committee of the University of Tuebingen, Germany (199/2007BO2), and all patients signed an informed consent upon inclusion. ...
... The US7 score examination included the assessment of the following pathologic manifestations according to EULAR criteria [31] and OMERACT definitions [10] for greyscale (GS) and power Doppler (PD) ultrasound: ...
Article
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Background: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. Methods: RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test and Cochrane-Q test respectively, including the comparison of palmar vs. dorsal regions (chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response means (SRM)/linear regression. Analyses were also performed separately for early and established RA. Results: A total of 435 patients (N = 138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p ≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p < 0.001) and the palmar side of the finger joints by PD (p < 0.001) were more frequently pathologic. The reduced US7 score (GS/PD: palmar MCP2, dorsal wrist, EDC and ECU, only PD: dorsal MCP2) showed therapy response (SRM 0.433) after 6 months and retained 76% of the full US7 score's information. No major differences between the groups of early and established RA could be detected. Conclusions: The wrist, MCP2, EDC, and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.
... RF is historically the first autoantibody associated with RA and has long been the sole serological marker for RA [12][13][14]. RF are autoantibodies that bind to epitopes within the constant region (Fc) of immunoglobulin type G (IgG). Besides RA, RF can also be detected in other rheumatic disorders, infections and in apparently healthy individuals with an incidence that increases with age [15,16]. ...
... Consequently, RF has a low overall specificity (± 80%) for RA [17,18]. Of note, the 1987 classification criteria stated that the diagnostic specificity of any RF test should be >95% when tested in healthy controls [14]. The sensitivity of RF for RA is ± 60% [1,18]. ...
Article
Objectives: Rheumatoid factor (RF) is a well-established marker for the diagnosis and classification of rheumatoid arthritis (RA). Most studies evaluated IgM RF or isotype-nonspecific total RF assays. We evaluated the added value of IgA RF in this context. Methods: An international sample cohort consisting of samples from 398 RA patients and 1073 controls was tested for IgA RF with 3 commercial assays. For all RA patients and 100 controls essential clinical and serological data for ACR/EULAR classification were available. Results: The sensitivity of IgA RF for diagnosing RA was lower than the sensitivity of IgM RF. Differences in numerical values between IgA RF assays were observed. With all assays, the highest IgA RF values were found in patients with primary Sjögren's syndrome. Double positivity for IgM RF and IgA RF had a higher specificity for RA than either IgM RF or IgA RF. The sensitivity of double positivity was lower than the sensitivity of either IgA RF or IgM RF. Single positivity for IgA RF was at least as prevalent in controls than in RA patients. Adding IgA RF to IgM RF and anti-citrullinated protein antibodies (ACPA) did not affect RA classification. However, combined positivity for IgA RF, IgM RF and IgG ACPA had a higher specificity and lower sensitivity for RA classification than positivity for either of the antibodies. Conclusions: IgA RF showed a lower sensitivity than IgM RF. Combining IgA RF with IgM RF and ACPA did not improve sensitivity of RA classification. Combined positivity (IgA-RF/IgM-RF/ACPA) increased specificity.
... This cross-sectional study was approved by the local ethics committee "Comitato Etico Milano Area 2" (approval code: 591_2020 bis). The study population consisted of all consecutive patients (aged > 18 years) with RA [44,45], SpA [46,47], or primary OA referred to the Division of Clinical Rheumatology, ASST Pini-CTO for aspiration of joint effusion and subsequent drug injection, as part of the therapeutic procedures in clinical practice. After signing the informed consent, the subject's eligibility was verified, data was collected and coded. ...
Article
Background Accumulating evidence suggests that poor mental health is one of the most common comorbidities of both rheumatoid arthritis (RA) and osteoarthritis (OA) [1]. Even if underpinning RA and OA are different genetic, structural, mechanical, and immunologic pathways involved in their pathogenesis, poor mental health, and joint involvement are intertwined and negatively affect their mutual course by contributing to global disability. Thus, new insights into mechanisms that link these disorders are needed to identify new actionable biomarkers to drive more personalized therapeutic strategies. Amidst potential mediators, extracellular vesicles (EVs) play a central role in terms of communication between cells, they cross the blood-brain barrier and based on their cargos can affect the recipient cell function [2]. Objectives To isolate EVs from synovial fluid (SF) in RA and OA patients and to evaluate if and how these EVs can alter in vitro synaptic transmission of murine hippocampal neurons. Methods In this cross-sectional pilot study, consecutive adult RA and primary OA who were referred to the Rheumatology Unit for aspiration of joint effusion were enrolled. Demographic and clinical variables and mental health rating scales were collected. Discarded SF were collected and EVs were isolated and analyzed by Malvern NanoSight NS300 system to obtain information on their number and size. Afterwards, DIV14 cultured wild-type hippocampal neurons were exposed for two hours to OA- and RA-EVs at low and high concentration EVs. Thus, miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs), which reflects glutamatergic and GABA-ergic activity respectively, were examined by exploiting patch-clamp recordings in the whole-cell configuration. Frequency and amplitude were analyzed to evaluate potential changes at the presynaptic or postsynaptic compartment. Mann Whitney test was used to compare two different samples. Results Eight RA patients (7 female, mean age 57 yrs), and 5 primary OA (4 female, mean age 60 yrs) were recruited for SF aspiration. The mean VAS pain was 7.25 in RA and 6.5 in OA. No statistically significant differences were found between the two groups in mean rating scale scores although patients affected by RA had more severe depressive symptoms (Montgomery Asberg Depression Rating Scale -MADRS- means scores: 16.57) with respect OA group (MADRS mean scores: 10). The Nanoparticle tracking analysis showed that RA-EVs were significantly more in number compared to OA-EVs (Figure 1 A), mimicking more inflammation, while no significant difference in size was observed. Analysis of miniature events revealed the occurrence of two different changes. High concentration of OA-EVs has led to an increased amplitude of excitatory events, meaning an increased susceptibility of neurons to glutamate in the post-synaptic compartment (Figure 1 B). Whereas low concentration of RA-EVs has led to a decreased frequency of inhibitory events, which reflects a reduced function of GABA-ergic synapse in the pre-synaptic compartment (Figure 1 C). Figure 1. Conclusion Our results suggest that SF-derived EVs from OA and RA patients lead to different specific changes of neurotransmission, with different concentration needed to alter neuronal spontaneous activity in post-synaptic and pre-synaptic compartment, respectively. EVs may provide insight into the pathogenesis of joint-brain communication in RA and OA, unraveling specific pathways thus allowing targeted therapies for neuropsychiatric involvement. References [1]Lancet 2017;390(10100): 1211–1259 [2]FASEB Bioadv 2021;3(9):665-675 Disclosure of Interests Lavinia A. Coletto: None declared, Francesca Ingegnoli: None declared, Clara Cambria: None declared, Laura Cantone: None declared, Orazio De Lucia: None declared, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Valentina Bollati: None declared, Massimiliano Buoli: None declared, Flavia Antonucci: None declared.
... A total of 173 RA patients (228 knees) underwent elective primary TKA at our institute between January 1, 2006 and December 31, 2018. All patients met the 1987 American College of Rheumatology (ACR) classification criteria 13 or the new ACR/European League Against Rheumatism (EULAR) diagnostic criteria. 14 A flow chart of case selection is provided in Figure 1. ...
Article
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This study aimed to investigate changes in and factors associated with perioperative serum C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients undergoing total knee arthroplasty (TKA) in the biologic era. A total of 173 patients (228 knees) with RA underwent elective primary TKA at our institute between January 1, 2006 and December 31, 2018. Of these, 214 cases among 161 patients were examined in this retrospective study after excluding 3cases among 3 patients who developed postoperative complications and 11 cases among 9 patients who were treated with tocilizumab. Factors associated with changes in CRP levels between baseline (preoperative) and day 7 after TKA [ΔCRP (0-7days)] were assessed by multiple regression analysis. Median (interquartile range) CRP levels were 0.69 (0.21, 1.82) mg/dl preoperatively, 5.66 (4.21, 7.61) mg/dl on postoperative day 1, 12.75 (9.79, 16.74) mg/dl on postoperative days 3-4, 3.26 (2.21, 4.85) mg/dl on postoperative day 7, and 0.87 (0.45, 1.81) mg/dl on postoperative day 14. Multivariate regression analysis revealed that body mass index ≥25 [partial regression coefficient (B)=1.03, P=0.012] and use of glucocorticoids (B=-0.86, P=0.017) were independently associated with ΔCRP (0-7days), whereas use of methotrexate and targeted drug modifying antirheumatic drugs and preoperative CRP levels (an objective biomarker of RA activity) were not. In conclusion, serum CRP levels increased rapidly after TKA and peaked on postoperative days 3-4, followed by a return to preoperative levels by postoperative day 14 in patients with RA. Obesity and the use of glucocorticoids were independently associated with changes in CRP levels.
... 1. Age ≥ 18 years old, no gender limit. 2. Patients with RA are diagnosed based on the RA classification criteria issued by the American College of Rheumatology (ACR) in 1987 [13] and the RA classification criteria issued by ACR/EULAR in 2010 [14]. 3. Patients with a maintenance dosage of adalimumab, etanercept, rituximab, infliximab, and other bDMARDs in the treatment of RA in the past 6 months. ...
Article
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Background To compare the effects of two biologic disease-modifying antirheumatic drug (bDMARD) administration strategies on the maintenance effect and safety of patients with rheumatoid arthritis (RA) in remission, to analyze the effects of gradual drug reduction and dose maintenance treatment on clinical outcomes in patients who have achieved remission with different types of bDMARDs, to search and screen out people who may benefit from drug reduction strategies, and to provide references for drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden. Methods The study will be a 24-month non-inferiority randomized, controlled, single-blind trial and is planned to be launched in our hospital from September 2021 to August 2023. Patients will be randomized in a ratio of 2:1 to two groups: maintenance or injection spacing by 50%/gradual reduction of dosage every 3 months up to complete stop. When the patient relapses, return to the last effective dose. If the remission can be maintained, the medication of bDMARDs can be stopped 9 months after enrollment. The primary outcome will be the persistent flare rate. Discussion Our study may provide a reference for the selection of drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden. Trial registration Chinese Clinical Trial Registry ChiCTR2100044751. Registered on 26 March 2021
... This cross-sectional study was approved by the local ethics committee "Comitato Etico Milano Area 2" (approval code: 591_2020 bis). The study population consisted of all consecutive patients (aged > 18 years) with RA [44,45], SpA [46,47], or primary OA referred to the Division of Clinical Rheumatology, ASST Pini-CTO for aspiration of joint effusion and subsequent drug injection, as part of the therapeutic procedures in clinical practice. After signing the informed consent, the subject's eligibility was verified, data was collected and coded. ...
Article
Full-text available
Arthritides are a highly heterogeneous group of disorders that include two major clinical entities, localized joint disorders such as osteoarthritis (OA) and systemic autoimmune-driven diseases such as rheumatoid arthritis (RA). Arthritides are characterized by chronic debilitating musculoskeletal conditions and systemic chronic inflammation. Poor mental health is also one of the most common comorbidities of arthritides. Depressive symptoms which are most prevalent, negatively impact patient global assessment diminishing the probability of achieving the target of clinical remission. Here, we investigated new insights into mechanisms that link different joint disorders to poor mental health, and to this issue, we explored the action of the synovial fluid-derived extracellular vesicles (EVs) on neuronal function. Our data show that the exposure of neurons to different concentrations of EVs derived from both RA and OA synovial fluids (RA-EVs and OA-EVs) leads to increased excitatory synaptic transmission but acts on specific modifications on excitatory or inhibitory synapses, as evidenced by electrophysiological and confocal experiments carried out in hippocampal cultures. The treatment of neurons with EVs membrane is also responsible for generating similar effects to those found with intact EVs suggesting that changes in neuronal ability arise upon EVs membrane molecules' interactions with neurons. In humans with arthritides, we found that nearly half of patients (37.5%) showed clinically significant psychiatric symptoms (CGIs score ≥ 3), and at least mild anxiety (HAM-A ≥ 7) or depression (MADRS and HAM-D ≥ 7); interestingly, these individuals revealed an increased concentration of synovial EVs. In conclusion, our data showing opposite changes at the excitatory and inhibitory levels in neurons treated with OA- and RA-EVs, lay the scientific basis for personalized medicine in OA and RA patients, and identify EVs as new potential actionable biomarkers in patients with OA/RA with poor mental health.
... ⩾18 years of age) and diagnosed with moderate or severe RA as per 2010 American College of Rheumatology (ACR) criteria. 35 Analysis of the 28-swollen joint count (SJC), the 28-tender joint count (TJC), patient global assessment (PtGA) score, physician global assessment (PhGA) score and C-reactive protein (CRP) was conducted to determine if drivers of remission in patients with comorbid depression and anxiety were potentially based on the more patient-orientated subjective-weighted measures (PtGA, TJC) as previously described. 14,15 Constituents of the Boolean-based remission criteria (i.e. ...
Article
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Background Rheumatoid arthritis (RA) is an inflammatory autoimmune condition associated with an increased risk of developing depression and anxiety. Depression and anxiety are associated with worse outcomes in RA, but the magnitude of the effect of each condition on RA outcomes is unclear. It is also unknown how pharmacological treatment of depression affects RA outcomes. Objective The primary aim of this study was to investigate the association of comorbid depression and anxiety with remission in patients with RA. Secondary aims were to determine the association between comorbid depression and anxiety on patient-reported outcomes and the relationship between concomitant use of antidepressants and remission in patients with depression. Design Data from patients with moderate to severe RA were pooled from five randomised controlled trials investigating tocilizumab and conventional synthetic disease-modifying agents. Methods Remission was defined as a clinical disease activity index (CDAI) of ⩽2.8 and simple disease activity index (SDAI) of ⩽3.3. The association between the time to reach remission and depression and anxiety was analysed using Cox proportional hazard analysis. Results Individual patient data were available from 5502 subjects, of whom 511 had depression, 236 had anxiety and 387 were using antidepressants. Depression was significantly associated with reduced remission [adjusted HR (95% CI): 0.62 (0.48–0.80), p < 0.001 and adjusted HR (95% CI): 0.59 (0.44–0.79), p < 0.001] using CDAI and SDAI, respectively. Depression was associated with a lower likelihood of achieving more subjective outcomes (⩽1 physician global assessment, ⩽1 patient global assessment) and ⩽1 28-swollen joint count, but not ⩽1 28-tender joint count or C-reactive protein measurement. Treatment with antidepressants did not improve outcomes for patients with depression. Anxiety was not significantly associated with RA remission. Conclusion Comorbid depression, but not anxiety, was associated with less frequent remission. Concomitant antidepressant use was not associated with improvements in RA outcomes in patients with depression.
... All patients fulfilled the 2010 diagnostic criteria of the American College of Rheumatology/European League Against Rheumatism (ACR/ EULAR) or the 1987 diagnostic criteria of the ACR. The enrolled patients had never been treated with MTX or biologic disease-modifying antirheumatic drugs (bDMARDs) [13,14]. Sjögren's syndrome (SS) was diagnosed according to the 2016 ACR/EULAR classification criteria [15]. ...
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Comparison of clinical response to methotrexate between anti-SSA antibody-positive and -negative patients with methotrexate-naïve rheumatoid arthritis and investigate the reasons for the differences in the response. For this multicenter retrospective cohort study, a total of 210 consecutive patients with rheumatoid arthritis who newly initiated methotrexate were recruited. The effects of anti-SSA antibody positivity on achieving a low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein after 6 months of methotrexate administration were investigated using a logistic regression analysis. This study involved 32 and 178 anti-SSA antibody-positive and -negative patients, respectively. The rate of achieving low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein at 6 months was significantly lower in the anti-SSA antibody-positive group than in the anti-SSA antibody-negative group (56.2% vs. 75.8%, P = 0.030). After 6 months, anti-SSA antibody-positive patients had significantly higher scores on the visual analogue scale (median [interquartile range]: 22 [15–41] vs. 19 [5–30], P = 0.038) and were frequently prescribed nonsteroidal anti-inflammatory drugs (37.5% vs. 18.0%, P = 0.018). In conclusion, the presence of anti-SSA antibodies might be a predictive factor for insufficient responses to treat-to-target strategy in rheumatoid arthritis. Residual pain might contribute to the reduced clinical response to methotrexate in anti-SSA antibody-positive patients with rheumatoid arthritis.
... All patients signed an informed consent form. The RA patients met the American College of Rheumatology 1987 diagnostic criteria and the American College of Rheumatology/European League Against Rheumatism 2010 diagnostic criteria for RA[30,31]. Clinical and laboratory features in patients with RA and OA and HC subjects were shown in Supplementary Table 1 (synovia) andTable 3(synovial tissue samples), respectively. ...
Article
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Abnormal activation of synovial fibroblasts (SFs) plays an important role in rheumatoid arthritis (RA), the mechanism of which remains unknown. The purpose of our study is to comprehensively and systematically explore the mechanism for Semaphorin 5A-mediated abnormal SF activation in RA. Here, we found that Semaphorin 5A levels were significantly higher in synovial fluid and synovial tissue from RA patients compared with osteoarthritis patients. We further found that the mRNA level and protein abundance of Plexin-A1 was elevated in RA SFs compared with OA SFs, while Plexin-B3 expression showed no significant difference. The increased Semaphorin 5A in RA synovial fluid was mainly derived from CD68+ synovial macrophages, and the elevation led to increased binding between Semaphorin 5A and its receptors, thereby promoting cytokine secretion, proliferation, and migration, and decreasing apoptosis. Moreover, the effect of Semaphorin 5A on enhancing activation (cytokine secretion, cell proliferation and migration) and reducing apoptosis of SFs was significantly abolished after knockdown of Plexin-A1 and Plexin-B3 by small interfering RNA. Transcriptome sequencing and protein array detection revealed that Semaphorin 5A activated the PI3K/AKT/mTOR signaling pathway and inhibited ferroptosis. Morphologically, transmission electron microscopy results showed that Semaphorin 5A could significantly eliminate the mitochondrial diminution, membrane density increased and crest ruptured of SFs induced by ferroptosis inducer RSL3. Mechanistically, Semaphorin 5A enhanced GPX4 expression and SREBP1/SCD-1 signaling by activating the PI3K/AKT/mTOR signaling pathway, thus suppressing ferroptosis of RA SFs. In conclusion, our study provided the first evidence that elevated Semaphorin 5A in RA synovial fluid promotes SF activation by suppressing ferroptosis through the PI3K/AKT/mTOR signaling pathway.
... The study included 45 female patients above 18 years old who were diagnosed with RA based on the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria or the 1987 ACR criteria [29,30]. All patients had active RA, with a 28 joint disease activity score (DAS28) >5.1 at the baseline, despite treatment with at least two synthetic disease-modifying antirheumatic drugs (DMARDs) for a minimum of 6 months with each drug. ...
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Sulfated glycosaminoglycans (sGAGs) are likely to play an important role in the development and progression of rheumatoid arthritis (RA)-associated atherosclerosis. The present study investigated the effect of anti-tumor necrosis factor-α (anti-TNF-α) therapy in combination with methotrexate on plasma sGAG levels and serum markers of endothelial dysfunction. Among sGAG types, plasma chondroitin/dermatan sulfate (CS/DS) and heparan sulfate/heparin (HS/H) were characterized using electrophoretic fractionation. Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and asymmetric dimethylarginine (ADMA) were measured by immunoassays. The measurements were carried out four times: at baseline and after 3, 9 and 15 months of anti-TNF-α therapy. All analyzed parameters, excluding ADMA, were significantly elevated in patients with RA before the implementation of biological therapy compared to healthy subjects. Performed anti-TNF-α treatment led to a successive decrease in HS/H levels toward normal values, without any effect on CS/DS levels in female RA patients. The treatment was also effective at lowering the serum levels of sVCAM-1, MCP-1, MMP-9 and ADMA. Moreover, a significant positive correlation was found between the circulating HS/H and the 28 joint disease activity score based on the erythrocyte sedimentation rate (DAS28-ESR, r = 0.408; p
... Historically, plain radiography has been the primary medical imaging technique to detect, characterize and monitor structural damage in RA patients. Before effective treatment became available, structural damages were common in late RA and presence of bone erosions at radiographs of the hands and wrists was a criterion for the classification of the disease proposed by the ACR in 1987 (Table VI.1) (4). The availability of disease-modifying anti-rheumatic drugs (DMARDs), first Methotrexate in the early 1990s and then biological DMARDs in the late 1990s, dramatically changed the clinical management of RA (3). ...
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The ideal MRI protocol to image hands of patients with rheumatoid arthritis (RA) would yield high sensitivity and specificity for the detection of early inflammatory changes and chronic structural damages of RA in a short acquisition time to optimize patient compliance. Currently recommended MRI protocols include multiple sequences with CHESS (Chemical Shift Selective) or STIR (Short Tau Inversion Recovery) fat suppression technique. We hypothesized that an MRI protocol including Dixon sequences could yield more effective fat suppression and higher image quality than the current recommended sequences while accurately assessing disease activity. As a first result, our studies consistently demonstrated more robust fat suppression and higher image quality with Dixon- than with CHESS-based MRI protocols to image hands of healthy subjects and RA patients at the cost of a longer imaging time. Second, we compared a set of multiple Dixon-based MRI sequences with the recommended set of multiple CHESS-based MRI sequences in a series of hands of patients with suspicion or early RA and demonstrated very good agreement between the two protocols for the assessment of synovitis, tenosynovitis, osteitis and erosions. Then, we compared the scores of disease activity obtained in hands of early RA patients by using either contrast-enhanced T1-weighted Dixon sequences or the recommended CHESS-based MRI protocol and demonstrated similar results of the two protocols for the assessment of disease activity suggesting that a short Dixon- based MRI protocol can be used for early RA assessment. Finally, we compared the assessability of hand cartilage by using the Dixon sequences in normal subjects and in RA patients. Out of the four available T1- weighted Dixon images, joint width measurements performed on Dixon out-of- phase images had the highest correlation coefficient with those on radiographs.
... FLSs were extracted and isolated from fresh synovial biopsies obtained from five RA patients undergoing finger, hand and pelvis arthroplasties. All patients satisfied the 1987 American Rheumatism Association criteria for RA [33]. The mean age of the patients was 67.4 ± 4.9 years (range 60-72 years). ...
Article
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The effect of dimethyl sulfoxide (DMSO) in rheumatoid arthritis (RA) human fibroblast-like synoviocytes (FLSs) has been studied on five different samples harvested from the joints (fingers, hands and pelvis) of five women with RA. At high concentrations (>5%), the presence of DMSO induces the cleavage of caspase-3 and PARP-1, two phenomena associated with the cell death mechanism. Even at a 0.5% concentration of DMSO, MTT assays show a strong toxicity after 24 h exposure (≈25% cell death). Therefore, to ensure a minimum impact of DMSO on RA FLSs, our study shows that the concentration of DMSO has to be below 0.05% to be considered safe.
... Among the patients visiting the rheumatology clinic at the Samsung Medical Center in Seoul, Korea between May 2001 and September 2007, 11 patients with RA and 8 with OA who underwent knee arthrocentesis were recruited for this study. They were diagnosed by experienced rheumatologists, based on the fulfillment of the 1987 American College of Rheumatology (ACR) classification criteria for RA (Arnett et al., 1988), and the ACR clinical classification criteria for OA of the knee (Altman et al., 1986). Medical records were reviewed for age, sex, duration of disease, radiographic findings of the knee-joints, and laboratory data regarding factors such as rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). ...
Article
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Introduction Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. Objectives We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. Methods We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. Results We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. Conclusion Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.
... The methods were performed in accordance with the approved guidelines. We collected synovial tissues from patients with rheumatoid arthritis (RA) who fulfilled the classification criteria of the American College of Rheumatology 1987 (Arnett et al. 1988). Synovial tissues were harvested from patients with RA who underwent total joint replacement or synovectomy after they provided informed consent and signed a written consent form. ...
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Studies conducted using murine arthritis models have indicated that the use of in vitro-transcribed messenger RNA (IVT mRNA) is an effective therapeutic approach for joint diseases. However, the use of IVT mRNA in human synovial cells has not been widely studied. Recently, the outbreak of the novel coronavirus disease has accelerated the development of innovative mRNA vaccines, such as those containing a modified nucleic acid, N¹-methylpseudouridine-5′-triphosphate (m1ψ). IVT mRNA is an attractive tool for biological experiments and drug discovery. To verify the protein expression from IVT mRNA in vitro, primary cultured fibroblast-like synoviocytes (FLS) and MH7A human synovial fibroblast cells were transfected with enhanced green fluorescent protein (EGFP) mRNA with or without m1ψ incorporation. EGFP was detected using western blotting and fluorescence microscopy. A multiplex assay was performed to comprehensively understand IVT mRNA-induced immunogenicity. Gene expression levels were measured using reverse transcription polymerase chain reaction. In both MH7A cells and FLS, cells transfected with EGFP mRNA containing m1ψ generated higher levels of EGFP than those transfected with unmodified EGFP or control mRNAs. The multiplex assay of the FLS culture supernatant and reverse transcription polymerase chain reaction for FLS revealed that both concentration and expression of IL-6, TNF-α, and CXCL10 were upregulated by unmodified EGFP mRNA, whereas they were suppressed by EGFP mRNA with m1ψ. Overall, m1ψ incorporation enhanced protein expression and decreased the expression of cytokines. These findings may contribute to arthritis research.
... All patients with SLE within the studies should satisfy one of the classification criteria of the American College of Rheumatology (ACR) 1982/1997 criteria (Hochberg, 1997) or the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria (Petri et al., 2012). All patients with RA within the studies should satisfy the classification criteria of the American Rheumatism Association (ARA) 1987 criteria (Arnett et al., 1988) or the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria (Aletaha et al., 2010). All patients with SS should satisfy the classification criteria of the ACR/EULAR 2016 criteria (Shiboski et al., 2017) or the American-European Consensus Group (AECG) 2002 criteria (Vitali et al., 2002) or the ACR 2012 criteria (Shiboski et al., 2012). ...
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Introduction: Despite decades of research, systemic autoimmune diseases (SADs) continue to be a major global health concern and the etiology of these diseases is still not clear. To date, with the development of high-throughput techniques, increasing evidence indicated a key role of oral microbiome in the pathogenesis of SADs, and the alterations of oral microbiome may contribute to the disease emergence or evolution. This review is to present the latest knowledge on the relationship between the oral microbiome and SADs, focusing on the multiomics data generated from a large set of samples. Methodology: By searching the PubMed and Embase databases, studies that investigated the oral microbiome of SADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), were systematically reviewed according to the PRISMA guidelines. Results: One thousand and thirty-eight studies were found, and 25 studies were included: three referred to SLE, 12 referred to RA, nine referred to SS, and one to both SLE and SS. The 16S rRNA sequencing was the most frequent technique used. HOMD was the most common database aligned to and QIIME was the most popular pipeline for downstream analysis. Alterations in bacterial composition and population have been found in the oral samples of patients with SAD compared with the healthy controls. Results regarding candidate pathogens were not always in accordance, but Selenomonas and Veillonella were found significantly increased in three SADs, and Streptococcus was significantly decreased in the SADs compared with controls. Conclusion: A large amount of sequencing data was collected from patients with SAD and controls in this systematic review. Oral microbial dysbiosis had been identified in these SADs, although the dysbiosis features were different among studies. There was a lack of standardized study methodology for each study from the inclusion criteria, sample type, sequencing platform, and referred database to downstream analysis pipeline and cutoff. Besides the genomics, transcriptomics, proteomics, and metabolomics technology should be used to investigate the oral microbiome of patients with SADs and also the at-risk individuals of disease development, which may provide us with a better understanding of the etiology of SADs and promote the development of the novel therapies.
... At the end of follow-up, all EA patients are classified as RA if they fulfil the 1987 ACR classification criteria [37] or as undifferentiated arthritis (UA) as described by Verpoort et al. [38]. Patients with other defined diagnoses (connective tissue diseases, psoriatic arthritis, gout, or osteoarthritis) are excluded from the study. ...
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Galectin 1 (Gal1) exerts immunomodulatory effects leading to therapeutic effects in autoimmune animal models. Patients with rheumatoid arthritis have been reported to show higher Gal1 serum levels than the healthy population. Our study aimed to find genetic variants on the Gal1 gene (LGALS1) modulating its expression and/or clinical features in patients with early arthritis (EA). LGALS1 was sequenced in 53 EA patients to characterize all genetic variants. Then, we genotyped rs9622682, rs929039, and rs4820293, which covered the main genetic variation in LGALS1, in 532 EA patients. Gal1 and IL-6 serum levels were measured by ELISA and Gal1 also by western blot (WB) in lymphocytes from patients with specific genotypes. Once disease activity improved with treatment, patients with at least one copy of the minor allele in rs9622682 and rs929039 or those with GG genotype in rs4820293 showed significantly higher Gal1 serum levels (p < 0.05). These genotypic combinations were also associated with higher Gal1 expression in lymphocytes by WB and lower IL-6 serum levels in EA patients. In summary, our study suggests that genetic variants studied in LGALS1 can explain heterogeneity in Gal1 serum levels showing that patients with higher Gal1 levels have lower serum IL-6 levels.
... Between December 2020 and the end of May 2021, samples were obtained from "the outpatient rheumatology unit" at Al-Sadder General Hospital in the province of Meisan-Iraq. In this case-control study, 104 obese volunteers between the ages of 40 and 71 years old with definite RA according to the ARA (American Rheumatism Association) criteria, [8] of whom were obese, took part. The participants were split into two groups, as follows: Forty-one patients (13 men and 28 women) with arthritis were paired with forty-four healthy blood donors (20 men and 24 women) who had no history of arthritis. ...
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Laboratory tests such as the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Immunoglobulin M (IgM) have been used as markers of inflammation and disease activity in rheumatoid arthritis (RA), although there is still no clear consensus on when to use one, the other, or all. We aimed to evaluate the level of OPG in RA patients compared with control in order to estimate the predictive value of OPG. Eighty five patients with active RA, attending rheumatology department at Al-Sadder General Hospital in the province of Maysan-Iraq, diagnosed according American College of Rheumatology (ACR) revised criteria were included. The patients' tender and swollen joint counts were calculated. Laboratory investigations were done including ESR by Westergren method, CRP, IgM and OPG by ELISA method, assessment of disease activity using DAS28 score. A non-significant change (p>0.05) was seen in the level of BMI, significantly increased (p<0.01) in levels of ESR, CRP, IgM, and OPG as compared to the control group. All patients showed disease activity at the time of the study, their DAS28 scores ranged from 5.20 to7.40 (Mean ±SD 6.43±0.80). There was a positive and highly significant (p< 0.01) correlation between DAS28 values and ESR, CRP, IgM, and OPG values (r-value was 0.662, 0.695, 0.689, and 0.636, respectively). The OPG was more specific than Rf (IgM, CRP, and ESR) in the diagnosis of RA. So it could be a useful assay in establishing the diagnosis of RA, especially in ambiguous cases or RF negative patients with RA, and also a better predictor of disease severity.
... Randomized controlled trials (RCTs) administering n-3 FA supplements in patients with RA were considered eligible for inclusion. Eligible trials included adult (>18 years of age) participants, diagnosed with RA based on the criteria defined by the American College of Rheumatology (ACR) (Arnett et al. 1988) or the ACR/European League Against Rheumatism (EULAR) criteria (Kay and Upchurch 2012). Eligible interventions were restricted to those including EPA and/or DHA, whereas additional nutrients (such as other n-3 FAs or vitamins) within the supplements were also permitted. ...
Article
Theoretical evidence and previous studies suggest that oralnutrient supplementation (ONS) with n-3 fatty acids for rheumatoid arthritis (RA) has the potential to lower disease activity indicators and non-steroidal anti-inflammatory drug (NSAID) uptake. A systematic search was conducted on five databases/registries from inception until May 23, 2021 with the aim to identify randomized placebo-controlled trials comparing n-3 supplements to placebo on disease-specific outcomes. A total of 23 studies matched the criteria (PROSPERO: CRD42019137041). Pooled analyses revealed that n-3 ONS provided a small effect in reducing pain [standardized mean difference (SMD): -0.16, 95% confidence intervals (CI): -0.40 to 0.09], and tender (SMD: -0.20, 95% CI: -0.46 to 0.05) and swollen joint count (SMD: -0.10, 95% CI: -0.28 to 0.07). In sensitivity analyses, there was a small effect in the reduction of NSAIDs intake (SMD: -0.22, 95% CI: -0.90 to 0.46), and c-reactive protein was reduced only by 0.21 mg/dL (95% CI: -0.75 to 0.33). Similar findings were observed regarding other objective/subjective outcomes. The certainty of the evidence was mostly of "very low/low" quality. Overall, n-3 ONS in RA might have a limited clinical benefit. Previous findings suggesting a reduction in NSAID intake may have been biased from the inadequate blinding of interventions.
... For the present study, samples from a total of 90 subjects were analyzed: 38 healthy donors (HD), 15 patients with psoriasis (PS), 8 with Graves' disease with ophthalmopathy (GD) defined by the EUGOGO criteria [61], 15 with spondyloarthritis (SpA) (8 fulfilled the New York classification criteria for ankylosing spondylitis [62], 2 had undifferentiated spondylitis fulfilled the Assessment of SpondyloArthritis International Society (ASAS) criteria for SpA [63], and 2 had psoriatic arthritis (PsA) who fulfilled the Classification Criteria for Psoriatic Arthritis (CASPAR) [64]), and 14 patients classified as having rheumatoid arthritis (RA) according to the 2010 EULAR/ACR criteria [65] who all fulfilled the 1987 diagnosis criteria for RA [66]. Written informed consent was obtained from all of them prior to their inclusion in accordance with the Declaration of Helsinki. ...
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Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves’ disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.
... The results of the therapy were assessed based on clinical signs and symptoms mentioned in the Ayurvedic classics. The improvements in the condition of patients were assessed based on Roga Bala, Agni Bala, Deha Bala, Chetasa Bala and as well as by American Rheumatism Association (ARA 1987) criteria for degree of disease severity [10]. ...
Article
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Background: Kshara Basti and Virechana Karma as therapy for Amavata are indicated in Ayurveda. Ayurveda is having a crucial role in the management of Amavata with special reference to rheumatoid arthritis (RA) as a crippling disease. Amavata is having clinical appearance as comparable with RA. The line of treatment as mentioned by Chakradatta is to bring Agni to normal state for digestion of Ama, eventually to eliminate vitiated Vata and Ama. Thus, here Kshara Basti and Virechana Karma are selected for the present study as Samshodhana process which corrects all the above captions. Objective: To evaluate and compare clinical efficacy of Kshara Basti and Virechana Karma as tharapy in Amavata. Methods: This was a randomized open-label, comparative clinical study. Total 35 randomly selected patients of Amavata were registered and screened and out of them 30 (15 patients in Group-A i.e. Kshara Basti and 15 patients in Group-B i.e. Virechan-Karma) were completed the treatment. Kshara Basti in the format of Kala Basti (as mentioned by Chakradatta) was given to the patients of Basti group and Virechana Karma as per Chakradatta was given to the patients of Virechana karma group. The effects of therapy in both groups were assessed by a specially prepared proforma. Results: The results of the study showed that both the groups showed significant relief in symptoms; however, compared to Virechana karma group, Basti group showed better result in the management of Amavata. Statistically significant improvement was found in ESR, RA factor (quantitative) and highly significant results were found in symptoms of Amavata (Kshara Basti results significant as compared to Virechana karma). Moderate improvement was seen in 80% of patients of Basti group (66.6% Virechana karma group), 6.6% patients got marked improvement in Basti group (no marked improvement in Virechana group), while mild improvement was found in 13.3% of patients of Basti group (33.3% for Virechana karma group). Conclusion: Kshara Basti and Virechana Karma have significant comparative activity in Amavata.
... It is considered to be rather a complex syndrome than a single disease entity and clinical symptoms as well as disease course vary greatly between patients further complicating exact diagnosis. Therefore, the American College of Rheumatology (ACR) listed seven criteria, of which at least four have to be fulfilled in order to qualify the diagnosis of RA [119]. The symptoms include morning stiffness, arthritis of 3 or more joint areas, arthritis of hand joints, symmetric arthritis, rheumatoid nodule formation, serum rheumatoid factor (RF) and radiographic changes. ...
Thesis
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Unravelling the genetic susceptibility to complex autoimmune diseases and understanding these pathologies on a mechanistic level are major obstacles to improve our possibilities for therapeutic intervention and an increase in the quality of life of affected patients. Studies in experimental rodent models, that can be run under stable environmental conditions, which itself can be subjected to experimental manipulation, and in cohorts of potentially unlimited size, hold significant promise for the understanding of genes and pathways involved in complex autoimmune diseases. In this thesis, which is based on five scientific manuscripts, we initially investigated the influence of the genetic background on the ability to detect three major genetic loci (Pia4/Cia12, Pia5/Cia3, Pia7/Cia13) for pristane induced arthritis (PIA) in the rat. We also investigated the effect of Pia1, which includes the RT1 region (major histocompatibility complex (MHC) in the rat). We could show that the major arthritis regulator NCF1 as well as the MHC are silent in certain genetic backgrounds, whereas their genetic effect on PIA susceptibility can be detected in other, distinct genetic setups, arguing for the importance of genetic interactions between MHC and non-MHC genes for PIA development. In the second and third paper, we used a unique approach with a heterogeneous stock (HS) derived inbred-outbred mouse cohort that had been backcrossed to the arthritis susceptible C57BL10/Q (BQ) mouse strain, in order to map clinical phenotypes and the autoantibody response during collagen induced arthritis (CIA) development. We defined numerous novel loci and fine mapped already described quantitative trait loci (QTL) associated with clinical disease and/or autoantibody production providing the to date most comprehensive mapping study in CIA. The papers 4 and 5 concern the positional identification of candidate genes for the CIA loci Cia21 and Cia22 in the mouse. We propose the costimulatory molecule CD2 as a female specific genetic risk factor for autommunity in the joint and the central nervous system (CNS). We also pinpoint the chitinase like gene Chi3l3, also denoted as Ym1, as an important immunomodulator in experimental murine arthritis models based on both active immunization with collagen (CII) and passive transfer of arthritogenic antibodies. Hopefully, the findings presented in this thesis will have clinical implications based on the novel genetic targets, we identified. In addition, our data demonstrate the difficulties and pitfalls that are associated with gene identification using a hypothesis free positional cloning approach in experimental rodent populations.
... (1) Participants: All patients over 18 with specific diagnostic criteria for RA (Arnett, 1988;Aletaha et al., 2010), with a balanced baseline and comparability. ...
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Objectives: We aimed to estimate the effectiveness and safety of iguratimod (IGU) monotherapy or in combination with methotrexate (MTX) in treating rheumatoid arthritis (RA) to provide an evidence-primarily-based foundation for clinical application. Methods: We conducted a systematic review of the meta-analysis using eight databases and two clinical trial websites searching for randomized controlled trials (RCTs) from conception to 15 March 2022, based on outcomes of patients with RA treated with IGU. The evidence quality assessment of primary outcomes was evaluated by the GRADE tool, and RevMan 5.3 and StataMP 14.0 were used to perform this research. Results: A total of 4302 patients with RA from 38 RCTs was included in this research. Pooled results demonstrated as follows: 1) Compared with methotrexate (MTX) alone, IGU alone was superior in improving ACR20 and DAS28-ESR, while having no significant difference in ACR50 and ACR70 [ACR20: (RR 1.15, 95% CI 1.05–1.27, p = 0.004); ACR50: (RR 0.97, 95% CI 0.66–1.44, p = 0.88); ACR70: (RR 0.92, 95% CI 0.45–1.90, p = 0.83); DAS28-ESR: mean difference (MD) −0.15, 95% CI −0.27 to −0.03, p = 0.01]. 2) Compared with MTX alone, IGU + MTX was more effective in improving ACR20, ACR50, ACR70, and DAS28-ESR. [ACR20: (RR 1.24, 95% CI 1.14–1.35, p < 0.00001); ACR50: (RR 1.96, 95% CI 1.62–2.39, p <0.00001); ACR70: (RR 1.91, 95% CI 1.41–2.57, p < 0.0001)]; [DAS28-ESR: (MD) −1.43, 95% CI −1.73 to −1.12, p < 0.00001]. 3) Compared with MTX + leflunomide (LEF), ACR20, ACR50, ACR70, and DAS28-ESR of IGU + MTX had no significant difference [ACR20: (RR 1.06, 95% CI 0.94–1.19, p = 0.38); ACR50: (RR 1.10, 95% CI 0.66–1.84, p = 0.72); ACR70: (RR 1.20, 95% CI 0.45–3.20, p = 0.71); DAS28-ESR: (MD −0.02, 95% CI −0.13 to −0.10, p = 0.77)]. 4) Compared with MTX + hydroxychloroquine (HCQ), IGU + MTX was superior in improving DAS28-ESR (MD −2.16, 95% CI −2.53 to −1.79, p < 0.00001). 5) Compared with MTX + tripterygium glycosides (TGs), IGU + MTX was more effective in improving DAS28-ESR (MD −0.94, 95% CI −2.36 to 0.48, p = 0.19). 6) There were no significant differences in adverse events (AEs) between the groups of IGU vs. MTX (RR 0.96, 95% CI 0.71–1.31, p = 0.80), IGU + MTX vs. MTX (RR 1.10, 95% CI 0.90–1.35, p = 0.34), IGU + MTX vs. MTX + HCQ (RR 0.64, 95% CI 0.29–1.42, p = 0.27), and IGU + MTX vs. MTX + TGs (RR 0.75, 95% CI 0.28–2.02, p = 0.57). The incidence of AEs in the IGU + MTX group was lower than the MTX + LEF group (RR 0.83, 95% CI 0.71–0.98, p = 0.03). Conclusion: Compared to the MTX alone subgroup, IGU alone offers clear advantages in improving ACR20 and DAS28-ESR, despite the insufficient evidence for DAS28-ESR findings. IGU + MTX shows clear benefits in improving ACR20, ACR50, ACR70, and DAS28-ESR scores compared to standard therapies. When the intervention (IGU alone or IGU + MTX) lasted for 52 weeks, it demonstrated superior efficacy in improving ACR20 of patients without prominent adverse events. Notably, IGU or IGU + MTX has apparent advantages in improving ACR20 of first-visit RA, and IGU + MTX has obvious advantages in improving DAS28-ESR of refractory RA. Furthermore, IGU + MTX does not increase the risk of leukopenia, but it can decrease the risk of liver function tests (LFTs), regardless of the age or the stage of RA. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails , identifier CRD42022295217
... Study inclusion was restricted to individuals born after 1931 and included in SRQ between 1999 and 2019. Early RA was defined as having symptom onset less than 12 months prior to diagnosis, where the diagnosis was ascertained by the treating rheumatologist per the ACR1987 or EULAR2010 criteria [24,25]. We excluded all individuals who, in NPR, had their first ever visit listing RA more than 365 days before their SRQ inclusion date. ...
Article
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Objectives To assess whether persistence to treatment with methotrexate (MTX) in early rheumatoid arthritis (RA) is shared among first-degree relatives with RA and to estimate any underlying heritability. Methods First-degree relative pairs diagnosed with RA 1999–2018 and starting MTX (in monotherapy) as their first disease-modifying anti-rheumatic drug (DMARD) treatment were identified by linking the Swedish Rheumatology Quality Register to national registers. Short- and long-term persistence to MTX was defined as remaining on treatment at 1 and 3 years, respectively, with no additional DMARDs added. We assessed familial aggregation through relative risks (RR) using log-binomial regression with robust standard errors and estimated heritability using tetrachoric correlations. We also explored the familial aggregation of EULAR treatment response after 3 and 6 months. To mimic the clinical setting, we also tested the association between having a family history of MTX persistence and persistence within the index patient. Results Familial persistence was not associated with persistence at 1 (RR=1.02, 95% CI 0.87–1.20), only at 3 (RR=1.41, 95% CI 1.14–1.74) years. Heritability at 1 and 3 years was estimated to be 0.08 (95% CI 0–0.43) and 0.58 (95% CI 0.27–0.89), respectively. No significant associations were found between family history and EULAR response at 3 and 6 months, neither overall nor in the clinical setting analysis. Conclusions Our findings imply a familial component, including a possible genetic element, within the long-term persistence to MTX following RA diagnosis. Whether this component is reflective of characteristics of the underlying RA disease or determinants for sustained response to MTX in itself will require further investigation.
... Synovial tissues were collected from ten RA patients (all females, mean age 60.2 ± 11.8 years) and five osteoarthritis (OA) patients (all females, mean age 64.2 ± 7.1 years) diagnosed according to the1987 ACR classification criteria for RA [29] or 1986 revised ACR classification criteria for knee OA [30] during total knee arthroplasty in the department of orthopedic surgery of Shanghai Jiao Tong University Affiliated Sixth People's Hospital. All the patients were not receiving any antirheumatic drug therapy at the time of surgery. ...
Article
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Background The upregulation of interferon (IFN)-stimulated genes induced by type I IFNs (namely type I IFN signature) in rheumatoid arthritis (RA) patients had implications in early diagnosis and prediction of therapy responses. However, factors that modulate the type I IFN signature in RA are largely unknown. In this study, we aim to explore the involvement of VGLL3, a homologue of the vestigial-like gene in Drosophila and a putative regulator of the Hippo pathway, in the modulation of type I IFN signature in the fibroblast-like synoviocytes (FLS) of RA patients. Methods FLS were isolated from RA and osteoarthritis (OA) patients. Expression of VGLL3 in the synovial tissues and FLS was analyzed by immunohistochemistry and PCR. RNA sequencing was performed in RA-FLS upon VGLL3 overexpression. The expression of IFN-stimulated genes was examined by PCR and Western blotting. Results VGLL3 was upregulated in the RA synovium and RA-FLS compared to OA. Overexpression of VGLL3 promoted the expression of IFN-stimulated genes in RA-FLS. The expression of STAT1 and MX1 was also upregulated in RA synovium compared to OA and was associated with the expression of VGLL3 in RA and OA patients. VGLL3 promoted the IRF3 activation and IFN-β1 expression in RA-FLS. Increased IFN-β1 induced the expression of IFN-stimulated genes in RA-FLS in an autocrine manner. VGLL3 also modulated the expression of the Hippo pathway molecules WWTR1 and AMOTL2, which mediated the regulation of IRF3 activation and IFN-β1 production by VGLL3 in RA-FLS. Conclusions VGLL3 drives the IRF3-induced IFN-β1 expression in RA-FLS by inhibiting WWTR1 expression and subsequently promotes the type I IFN signature expression in RA-FLS through autocrine IFN-β1 signaling.
... The samples were stored frozen at -80°C until the time of analysis. Patients with RA that met the American College of Rheumatology criteria for the disease were included in the study (22). The sample donors were patients with knee osteoarthritis (OA) and over 45 years of age with radiographic Kellgren/Lawrence grade ≥ 3 changes (23). ...
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Although recent studies have demonstrated a proinflammatory effect of extracellular histones in sepsis via endothelial cytotoxicity, little is known about their contribution to autoimmune arthritis. Therefore, we investigated the role of extracellular histones in autoimmune arthritis and their cytotoxic effect on synoviocytes and macrophages. We measured histones in the synovial fluid of patients with rheumatoid arthritis (RA) and evaluated arthritis severity in a serum-transfer arthritis (STA) mouse model with intraperitoneal histone injection. Histone-induced cytotoxicity was measured using SYTOX green staining in the synoviocyte cell line MH7A and macrophages differentiated from the monocytic cell line THP-1, and the production of damage-associated molecular patterns (DAMPs) was measured by HMGB1 and ATP. Furthermore, we performed RNA-seq analysis of THP-1 cells stimulated with H2B-α1 peptide or with its citrullinated form. The levels of histones were elevated in RA synovial fluid, and histones aggravated arthritis in the STA model. Histones induced cytotoxicity and DAMP production in synoviocytes and macrophages. Chondroitin sulfate reduced histone-induced cytotoxicity, while lipopolysaccharides aggravated cytotoxicity. Moreover, the cytotoxicity decreased when the arginines in H2B-α1 were replaced with citrullines, which demonstrated its electrostatic nature. In transcriptome analysis, H2B-α1 changed the gene expression pattern of THP-1 cells involving chemokines, interleukin-1, -4, -10, -13, and toll-like receptor (TLR) signaling pathways. Extracellular histones were increased in RA synovial fluid and aggravated synovitis in STA. They induced lytic cell death through electrostatic interaction with synoviocytes and macrophages, leading to the secretion of DAMPs. These findings suggest that histones play a central role in autoimmune arthritis.
Article
Rheumatoid arthritis (RA) is a chronic autoimmune disease that, when improperly treated, leads to disability in patients. Various factors that may cause the development and activity of RA are being considered. Epigenetic factors are also receiving increasing attention. In our study, we analyzed the association between FCER1G gene methylation and RA activity. We conducted our study in 50 RA patients and 24 controls. The patients were divided into two groups in terms of high disease activity and remission. Quantitative real-time methylation-specific PCR was used to analyze the methylation status of the investigated genes. We observed that RA patients have lower levels of methylation of the FCER1G gene compared to controls, but we did not find any difference in the methylation status of this gene between patients with high disease activity and remission. The results of this study suggest that FCER1G gene methylation may be a new potential epigenetic marker of RA that is independent of disease activity.
Article
Aim: To examine the global upper extremity kinematics in 3D while performing "jar opening motion" in Rheumatoid Arthritis (RA) and to compare these with healthy individuals. Method: Twenty-four women (12 healthy, 12 RA) were included. Evaluations were made with a JAMAR dynamometer, Health Assessment Questionnaire, and 3D kinematic analysis of global upper extremity during "jar opening motion." The time taken during "jar opening motion" was analyzed in 2 parts (Part 1, Part 2), with total time: part 1 + part 2. In addition, shoulder-to-table distance; elbow flexion angle; wrist extension angle; the area scanned and angular rotation by arm, forearm and hand were used in the analysis. Results: Between groups, there was a statistical difference in: bilateral hand grip strength; part 1, part 2, total time; shoulder-to-table distance; elbow flexion angle; the area scanned by hand; angular rotation of arm and hand in favor of the healthy group (P < .05). In stepwise multiple regression analysis, the most predictive variable for disability was elbow flexion, explaining 53.9% of disability. Conclusion: Compared to healthy individuals, individuals with RA have slower motion, more elbow flexion, less hand grip strength, circular pattern in hand, rotation in arm and hand. Increased disability may result in greater load on elbow flexion.
Article
Objective : Methotrexate (MTX) remains the first-choice disease-modifying therapy in rheumatoid arthritis (RA). However, clinical response is variable, and no reliable predictive biomarkers of efficacy currently exist. In this study, plasma metabolomic profiling is evaluated as a tool to identify pretreatment biomarkers of MTX response in RA. Methods : Plasma collected from RA patients initiating MTX therapy (n=20) were analyzed by metabolomic profiling totaling 648 identified metabolites. Pretreatment metabolomic profiles were compared based on clinical response after 16-weeks of MTX therapy. Clinical response to MTX was defined by a clinically meaningful reduction in disease activity score in 28 joints (DAS28-ESR) of greater than 1.2. Results : Pretreatment plasma levels of 19 metabolites were found to differ (p<0.05) between RA patients based on response to MTX at 16-weeks. Spearman's correlation of pretreatment plasma metabolite levels with change in DAS28-ESR over the treatment period further supported three of the identified metabolites as associated with MTX response (p<0.05). The identified metabolite levels were all found to be lower in RA patients responsive to MTX but were not found to be intercorrelated. Receiver operating characteristic analysis of each of the identified metabolites, alone or in combination, demonstrated an excellent discrimination between responders and non-responders based on pretreatment plasma levels of nornicotine (AUC=0.84), N-methylisoleucine (AUC=0.82), 2,3-dihydroxybutanoic acid (AUC=0.82), and a combination biomarker panel score (AUC=0.98). Conclusion : Pretreatment plasma metabolomic profiling identified multiple metabolites associated with early response to MTX therapy in RA and represents a promising approach for the identification of clinical biomarkers of MTX response in RA.
Article
Introduction: A genome-wide association analysis revealed a rheumatoid arthritis (RA)-risk-associated genetic locus on chromosome 9, which contained the tumor necrosis factor receptor-associated factor 1 (TRAF1). However, the detail mechanism by TRAF1 signaled to fibroblast-like synoviocytes (FLSs) apoptosis remains to be fully understood. Materials and methods: Synovial tissue of 10 RA patients and osteoarthritis patients were obtained during joint replacement surgery. We investigated TRAF1 level and FLSs apoptosis percentage in vivo and elucidated the mechanism involved in the regulation of apoptotic process in vitro. Results: We proved the significant increase of TRAF1 level in FLSs of RA patients and demonstrated that TRAF1 level correlated positively with DAS28 score and negatively with FLSs apoptosis. Treatment with siTRAF1 was able to decrease MMPs levels and the phosphorylated forms of JNK/NF-κB in vitro. Moreover, JNK inhibitor could attenuate expression of MMPs and increase percentage of apoptosis in RA-FLSs, while siTRAF1 could not promote apoptosis when RA-FLSs were pretreated with JNK activator. Conclusions: High levels of TRAF1 in RA synovium play an important role in the synovial hyperplasia of RA by suppressing apoptosis through activating JNK/NF-kB-dependent signaling pathways in response to the engagement of CD40.
Article
To identify predictors of rheumatoid arthritis (RA) disease activity flare in RA patients who achieved low disease activity (LDA) or persistent remission from the observational Thai Army Rheumatoid Arthritis Cohort study. RA patients with persistent clinical remission, defined by disease activity score 28 (DAS28) < 2.6 and LDA defined by DAS28 ≤ 3.2 for 3 consecutive months, were recruited and followed-up for at least 2 years. The flare was defined by an escalation of DAS28 ≥ 1.2 plus their physicians’ decision to enhance RA treatment. Differences between sustained remission/LDA and flare groups were analyzed, by Chi-square test and unpaired Student t test. Multivariate Cox proportional hazard regression analysis was conducted to determine flare predictors. From 199 RA patients, female were 82.9%. Anticitrullinated peptide antibodies (ACPA) or Rheumatoid factor (RF) were found in 69.8% of patients. Flares occurred in 69 patients (34.9%). Multivariate analysis found that the timescale from symptoms emergence to DMARD commencement, the timescale from DMARD commencement to when RA patients showed remission/LDA, the occurrence of RF or ACPA, LDA (in contrast to remission) and the increased DAS28 score when remission/LDA was achieved and tapering DMARDs promptly when persistent remission/LDA was achieved were predictors of RA flares with hazard ratios of (95% confidence interval [CI]) of 1.017 (1.003–1.030), 1.037 (1.015–1.059), 1.949 (1.035–3.676), 1.926 (0.811–4.566), 2.589 (1.355–4.947), and 2.497 (1.458–4.276), respectively. These data demonstrated that early and aggressive DMARDs treatment approach could maintain remission espcially in seropositive patients. Tapering should be applied minimally 6 months after reaching remission.
Article
Objective We evaluated the performance of the revised classification criteria for assessing different systemic autoimmune rheumatic diseases and their overlap syndromes. Methods A total of 652 patients with or highly suspected of having systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM)/dermatomyositis (DM) or rheumatoid arthritis (RA) were included in this study. The 1997 revised American College of Rheumatology (ACR) and the 2019 European League Against Rheumatism (EULAR)/ACR criteria for SLE, the 1980 ACR and the 2013 ACR/EULAR criteria for SSc, the criteria by Bohan and Peter and the 2017 EULAR/ACR criteria for PM/DM, and the 1987 revised ACR and 2011 ACR/EULAR criteria for RA were used for disease classification. Results The old and new criteria and a clinical diagnosis were used to respectively classify 103, 106 and 105 SLE patients; 35, 47 and 58 SSc patients; 18, 23 and 33 PM/DM patients; and 297, 389 and 468 RA patients. Sensitivity increased from 82.9% to 92.4% in SLE, from 56.9% to 79.3% in SSc, from 54.5% to 66.7% in PM/DM, and from 62.6% to 80.8% in RA. SLE-SSc was the predominant type of clinical overlap syndrome, while SLE-RA was the most classifiable. Conclusion The revised classification criteria for all the diseases showed an improved sensitivity, and SLE-overlap syndrome was predominant, regardless of the criteria sets.
Article
Background Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis. Methods qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes. Results Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1. Conclusions Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.
Article
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Amavata is an autoimmune disorder caused by Ama and Vata resulting in Lakshanas like Agnimandhya, Angamarda, Aruchi, Trishna, Alasya, Gaurava, Jwara, Nidraviparyaya, Utsahahani, Sandhiruja, Sandhishotha, Sandhisparshasahatva and Sandhistabdhata.[1] Amavata is correlated to Rheumatoid Arthritis (RA) in modern dialect and characterized by pain, swelling, and stiffness of synovial joints, systemic features and extra-articular involvement. The prevalence of RA is 0.5-1% between the age group of 25-55 years after which it levels up until the age of 75 years.[2] To break the chain of pathogenesis, Amavata Chikitsa like Langhana, Swedana, Dipana, Pachana with Tikta –Katu dravyas and Shodhana are intended.[3] Shatyadi Kalka with Varshabhu Kashaya[4] as Anupana and Vaitarana Basti[5] were cited beneficial. Shatyadi Kalka contains Shati, Shunti and Varshabhu which are easily available and exhibits Vata-Kaphahara and Amapachana actions whereas Vaitarana Basti exhibit Amahara and Shulahara effect and administered after food to understand the response of therapy. The study combination was selected with a view that it may reverse the sequence of pathogenesis. Methods: Among 46 registered subjects, 30 completed the course of treatment. They were administered Shatyadi Kalka (12gms) with Varshabhu Kashaya (~50ml) as Anupana for 24 days in combination with Vaitarana Basti in form of Yoga Basti after food. For statistical analysis, parameters were assessed with Friedman‟s test; Wilcoxon sign rank test, Repeated Measures ANOVA and Paired t-Test. Results: There was a statistically significant improvement in the Primary and Secondary outcome measures of Amavata. Conclusion: Shatyadi Kalka with Varshabhu Kashaya as Anupana and Vaitarana Basti were found effective in the management of Amavata.
Article
Background: Observational studies suggested that dementia risk in patients with rheumatoid arthritis (RA) is higher than in the general population. Objective: To examine the associations of RA with cognitive decline and dementia, and neuroimaging biomarkers of aging, Alzheimer's disease, and vascular pathology in adult participants in the Mayo Clinic Study of Aging (MCSA). Methods: Participants with RA were matched 1:3 on age, sex, education, and baseline cognitive diagnosis to participants without RA. RA cases with MRI were also matched with non-cases with available MRI. All available imaging studies (i.e., amyloid and FDG PET, sMRI, and FLAIR) were included. The study included 104 participants with RA and 312 without RA (mean age (standard deviation, SD) 75.0 (10.4) years, 33% male and average follow-up (SD) 4.2 (3.8) years). Results: Groups were similar in cognitive decline and risk of incident dementia. Among participants with neuroimaging, participants with RA (n = 33) and without RA (n = 98) had similar amyloid burden and neurodegeneration measures, including regions sensitive to aging and dementia, but greater mean white matter hyperintensity volume relative to the total intracranial volume (mean (SD)% : 1.12 (0.57)% versus 0.76 (0.69)% of TIV, p = 0.01), and had higher mean (SD) number of cortical infarctions (0.24 (0.44) versus 0.05 (0.33), p = 0.02). Conclusion: Although cognitive decline and dementia risk were similar in participants with and without RA, participants with RA had more abnormal cerebrovascular pathology on neuroimaging. Future studies should examine the mechanisms underlying these changes and potential implications for prognostication and prevention of cognitive decline in RA.
Article
Rheumatoid arthritis (RA) is a multifactorial disease affecting the immune system and many tissues in the body. This study aimed to evaluate the effect of magnesium supplementation on insulin resistance and fasting blood sugar (FBS) of patients with RA. In this prospective uncontrolled before-after study, RA patients referring to Rheumatology clinics of Qom City from January 2020 to January 2021 were evaluated. First, the patients received the routine rheumatoid arthritis treatment including 5 mg Prednisolone and 200mg Hydroxychloroquine daily for 6 months and FBS and insulin levels were measured after. Then, they received the routine arthritis rheumatoid treatment in addition to 300 mg/day oral Magnesium sulfate for 6 months and then, FBS and insulin levels were measured. The Homeostasis Model Assessment of insulin resistance (HOMA-IR) was used for determining insulin resistance. Thirty five patients with RA and the mean age of 49.83±2.58 years were enrolled. Twenty eight cases (80%) were female and 7 cases (20%) were male. The mean HOMA-IR before and after consumption of oral magnesium were 3.04±0.29 and 2.43±0.19, respectively. Statistically significant differences were found between FBS, insulin and HOMA-IR before and after consumption of oral magnesium (p<0.05). Our data suggested that magnesium supplementation reduces FBS, insulin and HOMA-IR in patients with rheumatoid arthritis. Thus, magnesium supplements may be an alternative method for prevention of type 2 diabetes in RA patients.
Article
Objectives: We conducted the cross-cultural adaptation and validation of the Leeds Satisfaction Questionnaire (LSQ) for patients with rheumatoid arthritis (RA) in Korea. Methods: The adaptation of the LSQ from English into Korean was based on guidelines for cross-cultural adaptation for self-report measures. Patients with RA were recruited from an outpatient clinic of a university hospital in South Korea. Validation of the Korean-LSQ with Rasch models was carried out using WINSTEPS. Model fit was determined by Infit and Outfit statistics (≥0.50 and ≤1.50), including the separation index (≥2.00) and reliability index (≥0.80). Results: The data set comprised 125 patients (82.4% female), with median (interquartile range) age 49.0 (37-57) years, and disease duration of 2.5 (1.2-3.8) years. The total and subscale scores of the Korean-LSQ demonstrated excellent or good test-retest reliability (0.88 for total, 0.71-0.82 for subscales), and items in the scale also revealed a high internal consistency (α = 0.93). The six subscales of the Korean-LSQ were found to have a good fit to the Rasch model and good reliability (Person separation index = 2.63 and reliability index = 0.87; item separation index = 37.03 and reliability index >0.99). In addition, the unidimensionality of the scale was confirmed by the principal component analysis based on the Rasch residuals. Conclusion: Fit to the Rasch model confirmed that the construct validity, reliability, and unidimensionality of the LSQ were preserved following the adaptation into Korean. The Korean-LSQ is a valid and reliable tool for measuring satisfaction with care in Korean patients with RA.
Article
Introduction: Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate (DAS28ESR), DAS28 with C-reactive protein (DAS28CRP), and simplified disease activity index (SDAI) are widely used to assess disease activity as low, moderate, or high or in remission in patients with rheumatoid arthritis (RA). However, these indicators can generate inconsistent results, influencing treatment decisions and limiting comparisons across studies. We aimed to establish equations for conversion from DAS28ESR and DAS28CRP to SDAI. Methods: We conducted a retrospective study, including 933 outpatients who were simultaneously assessed using DAS28ESR, DAS28CRP, and SDAI. The patients were divided into a training set (70%) and a validation set (30%). We developed equations to convert DAS28ESR and DAS28CRP values into SDAI values by bisquare-weighted robust regression to obtain SDAI-DAS28ESR and SDAI-DAS28CRP. In addition to using kappa values to assess consistency, differences in disease activity classification between SDAI-DAS28ESR and SDAI-DAS28CRP were examined by the Stuart-Maxwell test and the Bowker test. Results: Two quadratic equations were developed as follows: SDAI-DAS28ESR = 1.168 × (DAS28ESR)^2 - 2.432 × (DAS28ESR) + 2.649 and SDAI-DAS28CRP = 1.2 × (DAS28CRP)^2 - 0.3522 × (DAS28CRP) - 0.6014. After applying the equations, the Stuart-Maxwell test and the Bowker test were no longer significant between SDAI-DAS28ESR and SDAI or between SDAI-DAS28CRP and SDAI. The kappa values increased from 0.57 to 0.73 between SDAI-DAS28ESR and SDAI and 0.76 to 0.86 between SDAI-DAS28CRP and SDAI. Conclusion: SDAI-DAS28ESR and SDAI-DAS28CRP are interchangeable with the SDAI on the group level, which will facilitate comparisons among studies. In addition, the equations improved consistency between indicators. Key Points • There is disagreement in assessing disease activity in patients with rheumatoid arthritis between Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate (DAS28ESR), DAS28 with C-reactive protein (DAS28CRP), and simplified disease activity index (SDAI). • We developed and validated two quadratic equations to convert DAS28ESR and DAS28CRP into SDAI. We found there was no longer significant difference in disease activity between indicators after applying the equations. • This work may allow comparisons across studies which use different indicators.
Article
Background: Cannabidiol (CBD), one major nonintoxicating phytocannabinoid from Cannabis sativa demonstrated anti-inflammatory effects in animal models of several inflammatory conditions, including arthritis. However, it is still unknown which cell types mediate these anti-inflammatory effects of CBD, and, since CBD binds to a plethora of receptors and enzymes, it is complicated to pinpoint its mechanism of action. In this study, we elucidate the effects of CBD on B cells and peripheral blood mononuclear cells (PBMCs) in respect to survival, calcium mobilization, drug uptake, and cytokine (IL-6, IL-10, and TNF) and immunoglobulin production. Methods: Modulation of intracellular calcium and drug uptake in B cells was determined by using the fluorescent dyes Cal-520 and PoPo3, respectively. Cytokine and immunoglobulin production was evaluated by enzyme-linked immunosorbent assay. PBMC composition and B cell survival after CBD treatment was assessed by flow cytometry. Results: B cells express two major target receptors for CBD, TRPV2 (transient receptor potential vanilloid 2) and TRPA1 (transient receptor potential ankyrin 1), which are not regulated by B cell activation. CBD increased intracellular calcium levels in mouse and human B cells, which was accompanied by enhanced uptake of PoPo3. These effects were not dependent on transient receptor potential channel activation. CBD increased the number of early apoptotic B cells at the expense of viable cells and diminished interleukin (IL)-10 and tumor necrosis factor (TNF) production when activated T cell independently. In PBMCs, CBD increased IL-10 production when B cells were activated T cell dependent, while decreasing TNF levels when activated T cell independently. In PBMC/rheumatoid synovial fibroblast cocultures, CBD reduced IL-10 production when B cells were activated T cell independently. Immunoglobulin M production was augmented by CBD when B cells were activated with CpG. Conclusion: CBD is able to provide pro- and anti-inflammatory effects in isolated B cells and PBMCs. This is dependent on the activating stimulus (T cell dependent or independent) and concentration of CBD. Therefore, CBD might be used to dampen B cell activity in autoimmune conditions such as rheumatoid arthritis, in which B cells are activated by specific autoantigens.
Article
Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren's syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.
Thesis
La polyarthrite rhumatoïde (PR) est une maladie rhumatismale de physiopathologie complexe, où l'interaction entre agents environnementaux et facteurs génétiques est susceptible de déclencher l'auto-immunité. A ce jour, seul le tabac, chez des patients génétiquement prédisposés, a été rapporté comme associé de façon reproductible au risque de PR. Bien que l'implication des hormones féminines soit vraisemblable, au vu des taux d'incidence plus élevés chez la femme que chez l'homme, les données de la littérature sont discordantes. Différentes études rapportent aussi une association entre excès pondéral et le risque de PR le plus souvent séronégative et chez les femmes. Dans ces études, seul l'indice de masse corporel est utilisé, bien qu'il ne représente pas la répartition corporelle du tissu adipeux qui semble être un élément plus important que l'excès de masse grasse lui-même.Les objectifs de ce projet doctoral étaient d'étudier les associations entre les expositions hormonales, les mesures anthropométriques et le risque de PR dans la cohorte prospective française E3N comptant 98 995 femmes dont 698 PR incidentes.Nos résultats suggèrent qu'un haut niveau d'expositions cumulées aux hormones féminines endogènes et exogènes tout au long de la vie des femmes est inversement associé au risque de survenue d'une PR après la ménopausées. Une trajectoire de silhouette constamment large de la puberté jusqu'à la péri-ménopause est associée à une augmentation de risque de PR chez les femmes non exposées au tabac.Ce projet a ainsi permis d'affiner les connaissances sur les impacts des expositions hormonales féminines cumulées et de la répartition du tissu adipeux sur le risque de PR. Nos résultats soutiennent aussi l'hypothèse selon laquelle les expositions, survenant tôt dans la vie, cumulées et persistantes sont impliquées dans la physiopathologie de la PR. Ces nouvelles données sur la distribution du tissu adipeux à des périodes charnières de la vie reproductive des femmes (puberté et ménopause) mettent en lumière les relations complexes entre fonctions adipocytaires, hormones sexuelles et réponses immunitaires.
Article
Purpose We investigated objective and patient-reported outcomes after resection arthroplasty or shortening oblique osteotomy (SOO) of the lesser metatarsals combined with arthrodesis of the first metatarsophalangeal (MTP) joint for severe rheumatoid forefoot deformities. Methods 17 feet from 14 women (mean age, 67.8 years) underwent resection arthroplasty of the lesser metatarsal heads (MTH resection group), while 13 feet from nine women and two men (mean age, 68.7 years) underwent SOO of the lesser metatarsals (MTH preservation group). Arthrodesis of the first MTP joint was performed in all cases. Mean follow-up in the MTH resection and preservation groups was 25.0 and 21.3 months, respectively. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) scale and self-administered foot evaluation questionnaire (SAFE-Q) scores. Results Mean total JSSF scale significantly improved from 53.4 to 76.4 in the MTH resection group ( p < .001) and from 50.1 to 74.2 in the MTH preservation group ( p = .002). Pain and pain-related and shoe-related SAFE-Q subscale scores significantly improved after surgery in both groups. In the MTH resection group, recurrence of painful callosities and claw toe deformity was observed in four and three feet, respectively. In the MTH preservation group, one patient experienced recurrence of painful callosities and one underwent revision surgery for IP joint dislocation. Conclusion Resection arthroplasty or SOO of the lesser metatarsals combined with arthrodesis of the first MTP joint achieved significant improvement with respect to pain relief, deformity correction, and footwear comfort.
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Anti-citrullinated protein antibodies (ACPAs) are highly specific for the diagnosis of rheumatoid arthritis (RA). However, about one-third of RA patients are negative for ACPAs, which presents a challenge to the early diagnosis of RA. The purpose of this study was to analyze differences in lymphocyte subsets and CD4+ T cell subsets between ACPA+ and ACPA- RA patients, and to evaluate the value of matrix metalloproteinase-3 (MMP-3) as a diagnostic and monitoring marker in ACA- RA patients. A total of 145 ACPA+ RA patients, 145 ACPA- RA patients, and 38 healthy controls (HCs) were included in this study. Peripheral lymphocyte subsets were detected using flow cytometry, and serum MMP-3 was detected using chemiluminescence. Information about joint symptoms, other organ involvement, and related inflammatory markers was also collected. The results showed that, compared to ACPA- RA patients, ACPA+ cases had greater imbalances between peripheral CD4+ T cell subsets, mainly manifested as an increase in T-helper 1 (Th1) cells (p < 0.001) and decrease in regulatory T (Treg) cells (p = 0.029). This makes these patients more prone to inflammatory reactions and joint erosion. MMP-3 levels in ACPA+ and ACPA- RA patients were significantly higher than in HCs (p < 0.001), and MMP-3 could effectively distinguish between ACPA- RA patients and HCs (area under the curve [AUC] = 0.930, sensitivity 84.14%, specificity 92.11%). MMP-3 was also a serum marker for distinguishing between RA patients with low and high disease activities. Further analysis showed that MMP-3 was positively correlated with the levels of inflammatory markers and disease activity, and negatively correlated with the levels of lymphocyte subsets. In addition, with improvements in the disease, MMP-3 levels decreased, and further increased as the patients started to deteriorate. In summary, our research showed that there was a mild imbalance between peripheral CD4+ T cell subsets in ACPA- RA patients. MMP-3 may be used as a potential marker for early diagnosis of ACPA- RA. MMP-3 was an important index for RA disease evaluation, disease activity stratification, and prognosis.
Article
Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA. Methods A total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4 ⁺ , CD19 ⁺ B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( −) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA). Results Patients with RA had higher percentages of CD4 ⁺ T, CD19 ⁺ B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF ⁺ or ACPA ⁺ patients exhibited elevated percentages of CD19 ⁺ B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF ⁻ /ACPA ⁻ and RF ⁺ /ACPA ⁺ patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different. Conclusion Th17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA. Key Points • Th17, Treg, and ILC subset dysregulations are present in patients with RA but may reflect inflammation rather than specific diseases and stages. • No difference for the distribution of Th17, Treg, and ILC subsets between RF ⁺ and RF − patients and between ACPA ⁺ and ACPA − patients. The screening spectrum of RF and ACPA serology should be expanded to elucidate the role of immune cells in RA pathogenesis.
Article
Background Shortened telomeres are associated with several different subtypes of interstitial lung disease (ILD), although studies of telomere length and ILD in rheumatoid arthritis (RA) are lacking. Methods Within the Veterans Affairs Rheumatoid Arthritis (VARA) registry, we performed cross-sectional and case-control studies of prevalent and incident ILD, respectively. We randomly selected a subset of RA patients with ILD and individually matched them to RA patients without ILD according to age, sex, and VARA enrollment date. Telomere length was measured on peripheral blood leukocytes collected at registry enrollment using quantitative PCR (T/S ratio). Short telomeres were defined as a T/S ratio in the lowest 10th percentile of the cohort. Results Our cross-sectional study cohort was comprised of 54 RA-ILD patients and 92 RA-non-ILD patients. T/S ratios significantly differed between patients with and without prevalent ILD (1.56 [IQR 1.30, 1.78] vs. 1.96 [IQR 1.65, 2.27], p < 0.001). Similarly, prevalence of ILD was significantly higher in patients with short vs. normal-length telomeres (73.3% vs. 32.8%, p = 0.002). Short telomeres were independently associated with an increased odds of prevalent ILD compared to normal-length telomeres (adjusted OR 6.60, 95% CI 1.78–24.51, p = 0.005). In our case-control analysis, comprised of 22 incident RA-ILD cases and 36 RA-non-ILD controls, short telomeres were not associated with incident RA-ILD (adjusted OR 0.90, 95% CI 0.06–13.4, p = 0.94). Conclusion Short telomeres were strongly associated with prevalent but not incident ILD among patients with RA. Additional studies are needed to better understand telomere length dynamics among RA patients with and without ILD.
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Objectives To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16 ⁻ monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group. Conclusions mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16 ⁻ monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.
Article
Background Exercise is advocated in the treatment of rheumatoid arthritis (RA). However, uncertainty around the acute effects of exercise on pain and inflammation may be stopping people with RA from exercising more regularly. Objectives To determine the acute effects of exercise on pain symptoms, clinical inflammatory markers, and inflammatory cytokines in RA. Design A systematic review of the literature. Data sources and methods Five databases were searched (PubMed, Cochrane Library, CINAHL, Scopus and SPORTDiscus); inclusion criteria were studies with acute exercise, a definite diagnosis of RA and disease characteristics assessed by clinical function (i.e., disease activity score, health assessment questionnaire and self-reported pain), clinical markers associated with inflammation (i.e., c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and inflammatory cytokines (i.e., interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)). Results From a total of 1544 articles, initial screening and full text assessment left 11 studies meeting the inclusion criteria. A total of 274 people were included in the studies (RA = 186; control = 88). Acute bouts of aerobic, resistance, and combined aerobic and resistance exercise did not appear to exacerbate pain symptoms in people with RA. Conclusion Post-exercise responses for pain, clinical inflammatory markers and inflammatory cytokines were not different between people with or without RA. Exercise prescription was variable between studies, which limited between-study comparisons. Therefore, future investigations in people with RA are warranted, which combine different exercise modes and intensities to examine acute effects on pain symptoms and inflammatory markers. Registration The PROSPERO international prospective register of systematic reviews – CRD42018091155.
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• Patients with clinical features of rheumatoid arthritis (RA) but negative rheumatoid factor (RF) present a diagnostic challenge. The seronegative spondyloarthropathy (SNSA) syndromes, previously believed to be "rheumatoid arthritis variants," eg, Reiter's syndrome and psoriatic arthritis, are now considered to be genetically separate from RA and have been shown to be closely associated with HLA-B27. This syndromic discrimination has raised question as to the validity of RF negative RA (ie, seronegative RA). Demographic, clinical, and roentgenologic features of seronegative RA and SNSA are compared. Also, more common diagnoses that may simulate seronegative RA are outlined according to onset age of arthritis. Recent concepts of RF positivity and HLA-DR4 correlations are reviewed. Multiple unknown factors contribute to the currently recognized syndrome of RA. Its diagnosis continues to rest on an aggregate of host, clinical, immunologic, and radiologic features. (Arch Intern Med 1983;143:2167-2172)
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For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or paraarticular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.
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The need for limiting definitions in the rheumatic disease field has been emphasized. Definitions must draw sharp lines between diseases and at the minimal severity at which a diagnosis is acceptable. This need is just as great for the clinician planning therapeutic trials as for the epidemiologist studying the distribution of disease in the population.
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Of 159 patients with either polymyalgia rheumatica, seronegative rheumatoid arthritis (RA) or an undifferentiated syndrome with features of both who were followed for at least 30 months, synovitis recurred in 57. Twenty of the 57 patients had one episode of polymyalgia and another that looked like RA. Recurrences responded to prednisone and no joint destruction was seen. Temporal arteritis was seen with both diagnoses. These observations suggest that a benign symmetric synovitis occurs in older patients and may present as polymyalgia or as a polyarthritis that resembles RA.
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Possible associations between HLA-DR4 and laboratory, radiographic, joint count, functional, and demographic measures of clinical status were analyzed in 154 white patients with rheumatoid arthritis. Overall, 65 percent of the patients were HLA-DR4 positive, similar to other series. HLA-DR4 was associated significantly with the presence of rheumatoid factor and more severe radiographic changes. HLA-DR4 was not associated with significant differences in demographic, joint count, or functional measures of clinical status. HLA-DR1 was not associated significantly with differences in the presence of rheumatoid factor, radiographic changes, or other measures of clinical status. Selective associations of HLA-DR4 with rheumatoid factor and radiographic scores were more marked in men than in women. Patients who were putatively homozygous for HLA-DR4 were all seropositive and had more severe radiographic changes than patients who were heterozygous for HLA-DR4.
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Four hundred ninety-eight long-distance runners aged 50 to 72 years were compared with 365 community control subjects to examine associations of repetitive, long-term physical impact (running) with musculoskeletal disability and medical service utilization in a cross-section study. Runners had less physical disability than age-matched control subjects (p less than 0.01) and maintained more functional capacity (p less than 0.001) as measured by a modified Health Assessment Questionnaire Disability Index. Runners sought medical services less often, but one third of the visits that they did make were for running-related injuries. No differences were found between groups in conditions thought to predispose to osteoarthritis and musculoskeletal disability. Ligamentous laxity and family history of arthritis were similar in both groups. Runners demonstrated better cardiovascular fitness and weighed less. Differences persisted after adjustment for age, occupation, and sex, and after inclusion or exclusion of subjects with major medical problems. Musculoskeletal disability appeared to develop with age at a lower rate in runners (0.003 units per year versus 0.028) than in community control subjects, and the decreased rate was observed with both lower extremity and upper extremity functions. These data suggest positive effects of systematic aerobic running activity upon functional aspects of musculoskeletal aging.
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For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.
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Clinically detectable joint swelling was found in 10 of 13 fully evaluated patients considered to have polymyalgia rheumatica. Five patients had some joint findings at disease onset. Knees were most commonly affected. Sternoclavicular involvement was seen in 3 patients. Joint effusions in 8 patients had 300-5,700 leukocytes/mm3 with a mean of 2,900. Six synovial biopsy specimens studied by light microscopy revealed mild to moderate synovial proliferation and chronic inflammation that was generally less severe than in typical rheumatoid arthritis. Electron microscopy identified microvascular changes and large amounts of vesicular and granular debris in lining cells. In 1 patient, a "fingerprint" pattern in the granular material was suggestive of the findings in some immune complexes. This still unexplained synovitis may, as previously suggested, be important in the pathogenesis of the polymyalgia rheumatica syndrome.
Article
Patients with clinical features of rheumatoid arthritis (RA) but negative rheumatoid factor (RF) present a diagnostic challenge. The seronegative spondyloarthropathy (SNSA) syndromes, previously believed to be "rheumatoid arthritis variants," eg, Reiter's syndrome and psoriatic arthritis, are now considered to be genetically separate from RA and have been shown to be closely associated with HLA-B27. This syndromic discrimination has raised question as to the validity of RF negative RA (ie, seronegative RA). Demographic, clinical, and roentgenologic features of seronegative RA and SNSA are compared. Also, more common diagnoses that may stimulate seronegative RA are outlined according to onset age of arthritis. Recent concepts of RF positivity and HLA-DR4 correlations are reviewed. Multiple unknown factors contribute to the currently recognized syndrome of RA. Its diagnosis continues to rest on an aggregate of host, clinical, immunologic, and radiologic features.
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Twenty-six of 31 patients with primary Sjögren's Syndrome who had longterm followup and fulfilled strict criteria for inclusion but were otherwise unselected had articular manifestations attributable to this disease. Articular manifestations preceded sicca symptoms in 10, were simultaneous in 7, and followed sicca symptoms in 9 patients. Involvement was polyarticular in the 26, symmetric in 22, intermittent in 21, and continuous in 5. Synovitis was detected in 24, but was usually mild. These articular manifestations of primary Sjögren's syndrome were generally mild and responded readily to nonsteroidal antiinflammatory agents.
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When a community-derived population of 840 rheumatoid arthritis patients was used to test the American Rheumatism Association's 11 diagnostic criteria for rheumatoid arthritis, these criteria divided patients into 3 reasonably distinct classifications (probable, definite, and classic). The severity of disease increased in direct proportion to the number of positive criteria. Three criteria involve invasive procedures that are rarely performed; they are unnecessary for effective use of the other 8 criteria. Although 256 possible combinations of these 8 criteria exist, the criteria function principally to classify patients into only 7 major clinical syndromes, each of which corresponds to a major clinical presentation. By identifying the logical interrelationships between criteria in this report, we have confirmed their applicability and provided insight into the manner by which criteria classify patients.
Are polymyalgia rheumatica and seronegative rheumatoid arthritis the same? (ab-stract) Arthritis Rheum (suppl) 30( I)
  • Sheets Pk
  • Healey
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Sheets PK, Healey LA: Are polymyalgia rheumatica and seronegative rheumatoid arthritis the same? (ab-stract) Arthritis Rheum (suppl) 30( I):S27, 1987
Classifi-cation and Regression Trees Aging, long-distance running, and the development of musculoskel-etal disability
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Breiman L, Friedman JH, Olshen RA, Stone CJ: Classifi-cation and Regression Trees. Belmont, CA, Wadsworth, 1984 I I. Lane NE, Bloch DA, Wood PD, Fries JF: Aging, long-distance running, and the development of musculoskel-etal disability. Am J Med 82:772-780, 1987
revision of diagnostic criteria for rheumatoid arthri-tis Population Studies of the Rheumatic Diseases
  • Ropes Mw
  • Cobb S R Jacox
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Ropes MW, Bennett GA, Cobb S, Jacox R, Jessar RA: 1958 revision of diagnostic criteria for rheumatoid arthri-tis. Bull Rheum Dis 9:175-176, 1958 Bennett PH, Wood PHN (editors): Population Studies of the Rheumatic Diseases. Amsterdam, Excerpta Medica, 1968, pp 417-478
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