[Show abstract][Hide abstract] ABSTRACT: Abstract Macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNFα) play a pivotal role in rheumatoid arthritis (RA). MIF is considered a relevant cytokine because it appears before TNFα in the inflammatory cascade thus stimulating TNFα production and MIF's relationship with traditional synthetic disease modifying antirheumatic drugs (sDMARDs) is unknown. In this cross-sectional study, we investigated the association of MIF and TNFα serum levels with methotrexate (MTX) and in combination with chloroquine (CLQ) and sulfasalazine (SSZ) in RA patients classified according to the ACR/EULAR 2010 criteria. Patients were divided into three groups: MTX-monotherapy group (n = 40), MTX combination therapy groups: MTX + CLQ (n = 41), and MTX + CLQ + SSZ (n = 42). MIF and TNFα serum levels were determined by ELISA. We found high levels of ESR, CRP, RF, and anti-CCP in all therapy groups. Furthermore, we subclassified 97 patients with established RA (≥2 years of disease duration) and found that TNFα serum levels were lower in the combination therapy group (MTX + CLQ + SSZ) in comparison with the monotherapy MTX group (16.7 pg/mL versus 13.6 pg/mL, p = 0.02). However, we did not find differences between sDMARD therapies in MIF serum levels. We did find a significant reduction in MIF serum levels in patients treated with oral steroids compared with patients without oral steroids (1.7 ng/mL versus 4.3 ng/mL, p < 0.001). In conclusion, this study supports the role of sDMARDs in modifying TNFα serum levels and oral steroids MIF serum levels. Nevertheless, we found that MIF serum levels are not modified by sDMARD treatment.
No preview · Article · Feb 2015 · Immunopharmacology and Immunotoxicology
[Show abstract][Hide abstract] ABSTRACT: Background Probiotics are live microorganisms administered primarily in fermented milk products that increase the viability of the microbiota, allow the physiological processes of the intestine and modulate the immune system.The probiotic L. casei Shirota has decreased the inflammatory response in mice with collagen-induced arthritis.
Objectives To determine the effect of Lactobacillus casei Shirota on the clinical manifestations, gastrointestinal symptoms and serum levels of pro and anti-inflammatory cytokines: TNF-α, IL-1 b and IL-10 in patients with active RA.
Methods We performed a controlled single blinded clinical trial that included 19 female patients with active RA (DAS >3.2), ≥18 years of age, with no other inflammatory rheumatic o infectious disease and on stable treatment (DMARDs and prednisone <10 mg/d) in the last 3 months. They were randomized to two groups: the study group was given fermented milk at a dose of 4×1010 CFU of L. casei Shirota per day for 6 weeks and a placebo group. Cutoffs were made at 0, 6 and 9 weeks, the latter as a washout period to see if the effect remained. DAS28-ESR, HAQ-DI, gastrointestinal symptoms with the validated Gastrointestinal Symptom Rating Scale questionnaire (GSRS) and serum levels of cytokines: TNFα, IL-1β and IL-10 (ELISA) were evaluated. Statistical analysis was performed with SPSS using nonparametric tests Kruskal Wallis and Mann-Whitney test.
Results We included 11 patients in the study group (51±12 years of age) and 8 patients in the placebo group (54±20 years of age). No statistical significance in clinical findings was observed between both groups, but patients in the study group did improvein HAQ DI values that decreased from 1.03±0.4 at week 0 to 0.58±0.4 and 0.51±0.5 at week 6 and 9 respectively (p<0.05). A favorable trend was observed in DAS28, 5.5±0.8, 5.2±0.9 and 4.9±1.1 at week 0, 6 and 9 respectively. An improvement in gastrointestinal symptoms was seen with a GSRS score of 8.4±4.8 at baseline that decreased to 3.8±2.3 at week 9 (p<0.05). Proinflammatory cytokine levels also tended to decrease and an increase in anti-inflammatory cytokines was seen but without statistical significance between baseline and end of study results, but neither when compared with the placebo group. No patient experienced side effects.
Conclusions These results suggest that probiotic L. casei Shirota may have beneficial additive effect when used to treat RA. However more studies are needed with a higher dose, longer period of time and a larger amount of patients to determine effects of L. casei Shirota.
Disclosure of Interest None Declared
No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Background Leading causes of death in systemic lupus erythematosus (SLE) are infections, kidney failure and cardiovascular disease. Although most infections are bacterial, there is a greater prevalence of tuberculosis (TB) secondary to multiple immunological abnormalities and immunosuppression. The tuberculin skin test (TST) and chest radiography are not sufficient to detect latent TB infection (LTBI) in this group of patients. Currently interferon-Yrelease assay (IGRAS): Quantiferon-TB Gold In-Tube ™ (QFT-GIT) and T-SPOT.TB ™ (T-Spot), have shown greater superiority to diagnose LTBI in immunocompetent patients but efficiency is unknown in immunosuppressed patients with SLE.
Objectives The objective of the present study is to evaluate the efficiency of IGRAS in screening for LTBI in patients with SLE.
Methods We performed a cross-sectional study that included patients with SLE according to the ACR criteria, ≥ 16 years old and signed informed consent; pregnant patients were not included, nor with active TB or with antituberculosis treatment. Patients underwent a questionnaire to obtain epidemiological and clinical data of SLE and TB, and TST and IGRAS were performed. The statistical analysis included descriptive arithmetic, chi square for categorical variables, Student’s t test for quantitative variables and kappa for concordance.
Results We reviewed a total of 106 patients with SLE, with a mean age of 34.7 ± 13.2 and 95% were female. A history of BCG was found in 90% and 84% presented a scar. Only 8% reported contact with TB patients and 12% were employees or residents of health or correctional institutions. A previous PPD was reported in 8%, of which 11% had a positive result. The 4% with previous diagnosis of TB had received treatment, 75% with lung and 25% with kidney involvement. Comorbidities: 28.3% with hypertension, 2.8% diabetes mellitus and 16% with dyslipidemia. In the present study 9% had a positive PPD, with an average of 5.53 ± 1.92 mm. The QFT-GIT test reported 14% positive, 10% indeterminate and 76% negative. The latter test average was 1.77 ± 0.68 IU / ml in general, 3.14 ± 2.85 in the group of patients with a positive test, 1.41 ± 3.04 in the indeterminate and 0.11 ± 0.11 in the negative group. A correlation between positive results of the two tests was 0.24.
Conclusions In our group of patients with SLE a significant number of positive tests was observed for the diagnosis of LTBI, finding a fair concordance between the two tests, but a large number of indeterminate tests were seen. Further studies are needed to determine the usefulness of these tests in SLE and the need for a lower cutoff of IGRAS in this type of patient.
References: Centers for Disease Control and Prevention. Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection — United States, 2010. MMWR 2010; 59: 1-26
Prabu V, Agrawal S. Systemic lupus erythematosus and tuberculosis: A review of complex interactions of complicated diseases. J Postgrad Med 2010; 56: 244-50
Disclosure of Interest: None Declared
No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: A traditional infectious disease vaccine is a preparation of live attenuated, inactivated or killed pathogen that stimulates immunity. Vaccine immunologic adjuvants are compounds incorporated into vaccines to enhance immunogenicity. Adjuvants have recently been implicated in the new syndrome named ASIA autoimmune/inflammatory syndrome induced by adjuvants. The objective describes the frequencies of post-vaccination clinical syndrome induced by adjuvants. We performed a cross-sectional study; adverse event following immunization was defined as any untoward medical occurrence that follows immunization 54 days prior to the event. Data on vaccinations and other risk factors were obtained from daily epidemiologic surveillance. Descriptive statistics were done using means and standard deviation, and odds ratio adjusted for potential confounding variables was calculated with SPSS 17 software. Forty-three out of 120 patients with moderate or severe manifestations following immunization were hospitalized from 2008 to 2011. All patients fulfilled at least 2 major and 1 minor criteria suggested by Shoenfeld and Agmon-Levin for ASIA diagnosis. The most frequent clinical findings were pyrexia 68 %, arthralgias 47 %, cutaneous disorders 33 %, muscle weakness 16 % and myalgias 14 %. Three patients had diagnosis of Guillain-Barre syndrome, one patient had Adult-Still's disease 3 days after vaccination. A total of 76 % of the events occurred in the first 3 days post-vaccination. Two patients with previous autoimmune disease showed severe adverse reactions with the reactivation of their illness. Minor local reactions were present in 49 % of patients. Vaccines containing adjuvants may be associated with an increased risk of autoimmune/inflammatory adverse events following immunization.
No preview · Article · Apr 2013 · Immunologic Research
[Show abstract][Hide abstract] ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease in the United States. Non-alcoholic steatohepatitis (NASH), the most severe form of NAFLD, has an increased risk for progression to cirrhosis and associated comorbidities such as cardiovascular disease. Metabolic syndrome (MS) including insulin resistance and obesity is central to the development of NASH. It is now estimated to affect 30% of adults and about 10% of children in the U.S. Hispanics are disproportionably affected with not only higher rates of originating from the liver as well as from the adipose tissue, the gut and the gastrointestinal tract. Thus, dysfunction of the adipose tissue through enhanced flow of free fatty acids and release of adipocytokines, and alterations in the gut microbiome generate pro-inflammatory signals that increase NASH progression. Additional 'extrahepatic hits' include dietary factors and gastrointestinal hormones. Within the liver, hepatocyte apoptosis, ER stress and oxidative stress are key contributors to hepatocellular injury. In addition, lipotoxic mediators and danger signals activate Kupffer cells which initiate and perpetuate the inflammatory response by releasing inflammatory mediators that contribute to inflammatory cell recruitment and development of fibrosis. Inflammatory and fibrogenic mediators include chemokines, the inflammasome and activation of pattern-recognition receptors.
[Show abstract][Hide abstract] ABSTRACT: Knee osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage components due to an imbalance between extracellular matrix destruction and repair. The proinflammatory cytokines involved in OA, TNFα and IL1β, are considered the major implicated. The aim of this study was to investigate the relationship between TNFα -308 and -238 polymorphisms with messenger RNA (mRNA) and soluble TNFα expression in knee OA patients and healthy subjects (HS). Case-control study involved 50 knee OA patients classified according to 1986 ACR Classification Criteria, as well as 100 HS. The Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne disability index were applied to OA patients. The -308 and -238 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism technique. The TNFα mRNA expression was quantified by real-time PCR using TaqMan method. The sTNFα levels were measured by enzyme-linked immunosorbent assay. The TNFα mRNA expression in knee OA patients was higher than in HS (1.56-fold). In addition, the TNFα mRNA expression was higher in carriers of G allele in the knee OA group for both polymorphisms. The sTNFα levels were increased in G/G versus G/A genotypes in both studied polymorphisms (p < 0.05). However, the TNFα -308 and -238 genotypes did not show statistical differences between groups. The G allele of TNFα -308 and -238 polymorphisms is associated with high mRNA and soluble expression in knee OA patients. However, it is not a marker of susceptibility in Western Mexico. Further studies are necessary to confirm these findings.
Full-text · Article · Oct 2012 · Clinical and Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The PTPN22 gene encodes lymphoid tyrosine phosphatase LYP, a potent negative regulator of T cell activation. Polymorphic variants of this gene have previously been associated with various autoimmune disorders. The +1858C/T single-nucleotide polymorphism (SNP) (rs2476601), in the exon 14 of the PTPN22 gene has been associated with susceptibility to RA in several population.
The aim of this work was to investigate whether the +1858C/T of the PTPN22 gene is associated with susceptibility to RA in Western Mexico population.
A total of 309 unrelated RA patients, classified according to American College of Rheumatology (ACR) 1987 criteria, as well as 347 controls residents from Western Mexico were recruited for this study. The DNA samples were genotyped for +1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA).
The frequency of +1858T risk allele was significantly increased in patients with RA compared with controls (p=0.001, OR=2.83, 95%CI=1.50-5.32). To confirm this results we established a comparison between subjects carrying of CT+TT genotypes versus those carrying CC genotype, between both groups (p=0.004, OR=2.65, 95%CI=1.33-5.36). Nevertheless, we not observed association of the +1858C/T PTPN22 gene SNP with clinical activity and functional disability in RA patients. Likewise, the +1858T variant in RA patients seropositive for anti-CCP antibodies, increased the risk for RA (p=0.008, OR=2.5, 95%CI=1.3-5.0) when we compared with controls; however, in the group of seronegative patients, no was found significant difference (p=0.1, OR=2.5, 95%CI=0.9-7.2).
Our results support the association of the +1858T risk allele of the +1858C/T PTPN22 polymorphism with susceptibility to RA and confirm that, in combination with anti-CCP antibodies, this SNP influence the autoimmune processes towards a development of RA in Mexican population.
Full-text · Article · Jun 2012 · Immunology letters
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to establish whether there is an association between the presence of FCGR3A V(176) polymorphism with SLE or its manifestations. We included 94 patients according to the 1982 ACR criteria as well as 98 controls matched by age and gender. The 11 ACR diagnostic criteria were analyzed on the clinical files. The polymorphism FCGR3A V(176) was determined by direct sequencing. There was not an association between the polymorphism FCGR3A V(176) with SLE or its main manifestations. The allelic frequency for F(176) was: 0.80 and 0.72 in cases and controls, respectively (P = 0.09, IC95%: 0.42-1.07); and the genotypic frequency in the group of cases was: 0.65 for homozygotes F(176)/F(176), 0.30 for heterozygotes and 0.05 for the homozygotes V(176)/V(176), while for the control group it was 0.53, 0.39 and 0.08, respectively. The polymorphism FCGR3A V(176) is not associated with SLE or any of its manifestations in patients with SLE from the West of Mexico.
Full-text · Article · Mar 2010 · Rheumatology International
[Show abstract][Hide abstract] ABSTRACT: Plasminogen activator inhibitor type 1 (PAI-1) is an inhibitor of plasmin production. Plasmin can directly or indirectly to degrade cartilage and bone matrix. The PAI-1
HindIII polymorphism has been associated with high PAI-1 plasma levels in myocardial infarction patients and control populations. Furthermore, it has been associated with the angiographic extent of coronary artery disease, but their involvement in other diseases is still uncertain. Here, we assessed the relationship between PAI-1
HindIII polymorphism and PAI-1 plasma levels in rheumatoid arthritis (RA). One hundred and twenty-five RA patients and 132 control subjects (CS) were included. Genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism technique and PAI-1 plasma levels were quantified using an ELISA kit. Not significant differences in genotype and allele frequencies between both studied groups were observed (P > 0.05). RA patients showed lower PAI-1 plasma levels (18.92 ± 12.94 ng/ml) than CS (23.68 ± 23.38 ng/ml), without significant difference (P = 0.299). However, in RA patients the C/G genotype carriers showed higher PAI-1 plasma levels (23.00 ± 13.81 ng/ml) with respect to C/C (16.77 ± 11.97 ng/ml) and G/G (10.47 ± 7.07 ng/ml) genotype carriers (P = 0.036). The PAI-1
HindIII polymorphism was not associated with RA susceptibility. However, the C/G genotype is associated with high PAI-1 plasma levels in RA patients.
Full-text · Article · Sep 2009 · Clinical and Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: The depressive symptoms are associated with chronic pain in this study. A cross-sectional study was performed. A visual analog scale was used to register pain intensity. Depressive symptoms were measured using the Center of Epidemiological Studies (CES-Dr) scale as modified by Eaton and reviewed for use in the Mexican population. The study included 245 patients, with a mean age of 46 years, 86.1% of whom were female. The prevalence of some degree of depression was 55.1%. Patients with fibromyalgia had the highest prevalence of symptoms of depression (78.38%) and major depression (29.73%). Stepwise multiple regressions indicated that the best model (r2 = 0.26) to predict the CES-Dr score included the global pain score (P < 0.0001) and education level (P < 0.004). The Cronbach's alpha of the CES-Dr was high (alpha = 0.888). There was moderate correlation (r = 0.442), P < 0.0001 of the CES-Dr numeric score with the intensity of global pain.
Full-text · Article · Dec 2008 · Rheumatology International
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is characterized by a progressive joint damage mediated mainly by tumor necrosis factor alpha (TNFalpha). We investigated the relationship of TNFalpha-308 and -238 polymorphisms with messenger RNA (mRNA) expression and soluble TNFalpha (sTNFalpha) in 50 RA and 100 healthy subjects (HS).
Clinical and laboratory assessments were performed. Spanish Health Assessment Questionnaire Disability Index, Spanish version of Arthritis Impact Measurement Scales and Disease Activity Score using 28 joint count indices were applied to RA patients. The TNFalpha-308 and -238 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The mRNA expression of TNFalpha was quantified by real-time polymerase chain reaction. The sTNFalpha levels were measured by enzyme-linked immunosorbent assay.
The TNFalpha-308 polymorphism showed an increased frequency of guanine (G)/adenine (A) genotype in RA versus HS (P = 0.03; 95% confidence interval, 1.05-8.08; odds ratio, 2.9) and also the A allele was more frequent in RA patients versus HS (P = 0.04; 95% confidence interval, 1.01-7.29; odds ratio, 2.7). The G/G genotype and also the G allele were more frequent in HS. No significant difference was observed in TNFalpha-238 polymorphism. Rheumatoid arthritis patients showed high TNFalpha mRNA expression (1.33-fold). The G/G genotype was associated with high mRNA and sTNFalpha levels in both TNFalpha polymorphisms. The correlation of sTNFalpha levels with C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Spanish Health Assessment Questionnaire Disability Index, and Spanish version of Arthritis Impact Measurement Scales, was observed.
The TNFalpha-308 polymorphism is a susceptibility marker to RA. The G/G genotype is associated with a high mRNA and soluble TNFalpha expression.
No preview · Article · Oct 2008 · Journal of Investigative Medicine
[Show abstract][Hide abstract] ABSTRACT: Objective: To describe the main features of spondylarthritis (SpA) in Mexicans. Material and methods: This is a cross sectional, descriptive study of the information was collected and stored on-line in the Registro de Espondiloartropatías de la Sociedad Española de Reumatología (REGISPONSER) between January, 2006 and December, 2007. Methods are described elsewhere in this number. Results: We included 172 patients (102 males [59.3%]; mean age ± standard deviation 38 ± 14 years). Most patients had ankylosing spondylitis; then, undifferentiated SpA. Age at onset was 28 ± 14 years; 30% had onset < 16 years; time to diagnosis was 5 years. Combined peripheral arthritis and axial involvement was the commonest disease pattern at onset (72.7%); 18% had uveitis. Treatment included tumour necrosis factor in 12%. The Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index were 4.5 and 4.0. Differences between ankylosing spondylitis, undifferentiated SpA, and psoriatic arthritis consisted of sex distribution, time to diagnosis, axial symptoms, upper limb arthritis, hip disease, tarsitis, and pain. Conclusion: The pattern of SpA in Mexicans is characterized by combined axial and peripheral involvement.
No preview · Article · Jan 2008 · Reumatologia Clinica Suplementos
[Show abstract][Hide abstract] ABSTRACT: We investigate the clinical association of tumor necrosis factor receptor 2 (TNFR2) M196R polymorphism with rheumatoid arthritis (RA) and knee osteoarthritis (OA). Acute phase reactants, lipid profile, sTNFR2 levels, disease activity-disability indexes, and TNFR2 M196R polymorphism were analyzed in 50 RA, 50 knee OA patients, and 120 healthy subjects (HS). The M/M genotype frequency was 0.74 (RA), 0.80 (OA), and 0.64 (HS). The M/R genotype frequency was RA (0.26), OA (0.20), and HS (0.29). The R/R genotype was observed only in HS (0.07). The M allele was associated with OA (P = 0.0137, OR = 2.43). Total cholesterol, triglyceride levels, apolipoprotein A-I and B showed significant differences (P < 0.05). The highest sTNFR2 levels were observed in RA and OA (P = 0.001), however M/M and M/R carriers do not correlate with sTNFR2 production. Our findings suggest an association of the M allele with knee OA. In addition, high sTNFR2 levels in RA and OA were found.
No preview · Article · Nov 2006 · Rheumatology International