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Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis

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Abstract

The clinical features of ankylosing spondylitis (AS) were compared in 63 HLA-B 27 positive (+) and 15 B27 negative (-) individuals with this disease. There were no differences in age at onset, functional class, degree of deformity, pain, severity of X-ray changes, or frequency of peripheral joint involvement or of reconstructive orthopedic surgery. These data demonstrated that skeletal manifestations of AS were essentially the same in B27(+) and (-) patients, and provide no evidence for the speculation that AS in B27(-) patients is milder or is a different disease from that occurring in B27(+) patients. On the other hand, acute anterior uveitis was found to be significantly more common in B27(+) patients, a fact suggesting that the "uveitis of AS" may in fact be an independent condition occurring in B27(+) individuals, rather than a manifestation of AS per se.

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... The initial symptoms of AS usually start in adolescence to early adulthood, and disease onset after the age of 45 is very uncommon [49]. Initial studies comparing the clinical characteristics of AS reported inconsistent results on the age of onset between patients with or without HLA-B*27 gene, some revealing no differences [50,51], while one study did show a younger age of onset for HLA-B*27 + patients [28]. The discrepancy between the results of these studies may be explained by their small sample sizes. ...
... In conclusion of these studies, one can say that HLA-B*27 appears to lower the threshold for developing the disease at an earlier age, but the pathogenic mechanism of this process remains unclear. [51]. Since then, the prevalence of musculoskeletal manifestations of AS including peripheral arthritis, hip arthritis, enthesitis, and dactylitis in HLA-B*27 + and HLA-B*27 − AS patients has been assessed in several studies, which is summarized in Table 2. ...
... Abundance of evidence exists revealing that HLA-B*27 is strongly associated with acute AAU irrespective of the presence or absence of coexisting AS [58]. The first report indicating a more frequent occurrence of AAU in HLA-B*27 + AS patients than their HLA-B*27 − counterparts was published in 1977 [51]. However, subsequent studies reported mixed results on such association [50,59]. ...
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Purpose of review: We review our current knowledge about the clinical features of patients with ankylosing spondylitis (AS) who possess HLA-B*27 versus those who lack this gene. Recent findings: ERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. A genetic study supports the existence of an HLA-B27-independent common link between gut inflammation and AS. It is unusual to observe familial occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, psoriasis, or IBD. Although there are many similarities among AS patients possessing HLA-B*27 versus those lacking this gene, the former group has a younger age of onset, a shorter delay in diagnosis, a better clinical response to tumor necrosis factor inhibitors, a greater familial occurrence, a greater risk for occurrence of acute anterior uveitis, and a lower risk for occurrence of psoriasis and IBD. ERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. It is unusual to observe occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, IBD, or psoriasis. A recent genetic study supports the existence of an HLA-B*27-independent common link between gut inflammation and AS.
... The importance, or lack thereof, of HLA-B27 in shaping the clinical phenotype and course of these patients remains unclear. Both acute anterior uveitis (AAU) and sacroiliitis have been reported to have an association with HLA-B27 [15,16]. Researchers in prior studies have also reported HLA-B27 as an indicator of a poor prognosis among all categories of JIA, with HLA-B27-positive patients having more inflammatory back pain [17], greater disease activity [18], and decreased likelihood of remission after 8 years of disease [19] than children with JIA who are HLA-B27-negative. ...
... HLA-B27positive children also had a higher disease activity as assessed by the JSpADA. Surprisingly, in contrast to adult studies, we did not find an association between HLA-B27 status and the presence of AAU [15,36]. However, in a recent study of patients with ERA in Patient/parent pain (n = 100); cJADAS (JADAS3-10) (n = 69) a Six subjects who had arthritis and enthesitis at diagnosis were excluded because they were missing HLA-B27 status. ...
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Background Enthesitis-related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA) defined according to the International League of Associations for Rheumatology (ILAR) criteria. We aimed to characterize the clinical features and treatment regimens in an inception cohort of children with ERA. Methods We performed a retrospective, cross-sectional, multicenter cohort study including subjects diagnosed with ERA between 1989 and 2012. Patients all fulfilled the ILAR criteria for ERA within 3 months of initial presentation to the rheumatology clinic. Differences in the prevalence of clinical criteria across study sites and by human leukocyte antigen (HLA)-B27 status were assessed using the Wilcoxon rank-sum or chi-square test, as appropriate. ResultsTwo hundred thirty-four children met the inclusion criteria. Their median age at diagnosis was 11.6 years, and 59% were HLA-B27-positive. Sixty-nine percent had enthesitis and arthritis at the time of diagnosis. Seventy-eight percent had a pauciarticular onset. The prevalence of all ILAR criteria at diagnosis, except arthritis and acute anterior uveitis, differed significantly across sites (all p < 0.01). Medication use varied significantly across sites for children with peripheral arthritis (p < 0.001), but not for sacroiliitis or enthesitis only. Nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs were the most commonly prescribed treatments, with anti-TNF agents primarily being initiation for sacroiliitis. HLA-B27 positivity was associated with male sex, higher active joint count, sacroiliitis, and higher disease activity at disease onset. Conclusions The majority of children had a pauciarticular onset, and several statistically significant clinical differences based on HLA-B27 status were identified. The observed heterogeneity in clinical presentation across sites reflects either true differences in patient populations or differences in how the ILAR criteria are being applied.
... The finding of a negative effect of HLA-B27 on the activity of spondyloarthritis was the opposite of the results from at least 7 studies that have considered the effect of HLA-B27 on the BASDAI in patients with AS [3][4][5][6][7][8][9] . We are aware of only one study which found that HLA B27 positive subjects with AS had less active disease 20 . ...
... Sex differences, however, do not account fully for the difference which we found between HLA-B27 positive and negative subjects (see Table 2). Most studies on the effect of HLA-B27 on disease activity were conducted before the recognition of AxSpA using the ASAS criteria [3][4][5][6][7][8] . HLA-B27 positivity greatly facilitates the diagnosis of AxSpA by the ASAS criteria. ...
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HLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but the effect of HLA-B27 on the activity of the broader category now called axial spondyloarthritis (AxSpA) is apparently the opposite. A modified Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity among 3435 patients with spondyloarthritis (SpA) who participated in a survey designed to assess the effect of their disease and its treatment on the susceptibility and severity of Covid-19. Chi square testing was used to compare BASDAI scores between HLA-B27 positive and negative subjects. 2836 survey respondents were HLA B27 positive. The average BASDAI for the HLA-B27 negative cohort was 4.92 compared to 4.34 for the HLA-B27 positive subjects. Based on linear regression, a subject’s sex could not fully account for the differing BASDAI score in HLA-B27 negative subjects compared to those who are HLA-B27 positive. The difference between B27 positive and negative subjects was skewed by those with a BASDAI score of one or two. HLA-B27 positive subjects were more than twice as likely to have a BASDAI score of 1 compared to HLA B27 negative subjects and about 60% more likely to have a BASDAI score of 2 (p < 0.0001). HLA-B27 positive subjects have less active spondyloarthritis compared to HLA-B27 negative subjects as measured by a BASDAI score. Our data indicate that patients with mild back pain and a diagnosis of AxSpA are disproportionately HLA-B27 positive. The HLA-B27 test facilitates the diagnosis of axial spondyloarthritis such that patients from a community survey with mild back pain may be disproportionately diagnosed as having AxSpA if they are HLA-B27 positive. The test result likely introduces a cognitive bias into medical decision making and could explain our observations.
... 1,2 Despite several genetic studies concerning the mechanism and activation process of HLA-B27, the real triggering act of this gene is still unknown. [4][5][6][7] There are several hypotheses for the role of HLA-B27 in the pathogenesis of AS and nr-axSpA. The most accepted one is the abnormal processing of antigenic peptides and endoplasmic reticulum stress resulting from the tendency of HLA-B27 to misfold and form homo-dimers. 2 The frequency of the HLA-B27 also varies in terms of ethnicity and geography. ...
... The discovery of a potential association between HLA-B27 and AS produces a series of clinical studies describing the geographical prevalence and its potential relationship with the disease activity. 2,4,6,10 In this study, we presented the prevalence of HLA-B27 positivity among patients with AS and nr-axSpA, and its association with disease activity. Although HLA-B27 positivity among the Turkish patients diagnosed with AS has been investigated before, this is the first study evaluating the HLA-B27 positivity among the patients with AS and nr-axSpA in Turkey. ...
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Objective: Human leukocyte antigen (HLA)-B27 is a genetic risk factor associated with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA). Although there are studies regarding the HLA-B27 prevalence in patients with AS in Turkey, there is insufficient information on the HLA-B27 prevalence in patients with n-axSpA. We aimed to evaluate the prevalence of HLA-B27 positivity among patients with AS and nr-axSpA, and its association with disease activity. Material and Methods: A cross sectional study was conducted on 860 participants (762 with AS and 98 with nraxSpA), fulfilling the modified New York criteria and/or Assessment of Spondyloarthritis International Society (ASAS) classification criteria. Disease activity was assessed through the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP). Results: HLA-B27 was positive in 69.3% of all patients, in 70.1% of patients with AS, and in 63.3% of patients with nr-axSpA. There was a significant difference in HLA-B27 positivity among the AS patients with a higher ASDAS and higher BASDAI score (respectively; p<0.001, p=0.002), while there was no relation between the HLA-B27 positivity and disease activity in patients with nr-axSpA (p=0.6, p=0.5, respectively). Conclusion: The prevalence of HLA-B27 is relatively low among patients with AS and nr-axSpA in Turkey, which might be attributed to the geographic location of Turkey leads a multi-ethnic society. Moreover, HLA-B27 is associated with higher disease activity in AS patients, but there is no such relationship in nr-axSpA patients.
... Our findings, in parallel with those studies, presumably indicate the absence of any potential relationship of disease severity and age with MHC (major histocompatibility complex) group genes including HLA-B27 (8). Some recent clinical studies proved the relationship between HLA-B27 positivity and the early onset of symptoms; however, some studies reported a negative relationship (11,12). In the present study, there was no significant relationship between the age of disease onset and HLA-B27 positivity. ...
... According to Feldtkeller et al. (10), there is a positive relationship between HLA-B27 positivity and uveitis involvement in AS patients. Another study, by Khan et al. (11), revealed predominantly increased anterior uveitis incidence among cases with HLA-B27 positivity. In our study, only 7.9% of the total cases had uveitis. ...
Article
Objective: Human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis (AS). However, the association between clinical findings and HLA-B27 vary in terms of geographic area. This study aimed to determine the frequency of HLA-B27 positivity and its relationship with clinical findings. Material and methods: All subjects fulfilling the modified New York diagnosis criteria for AS enrolled in study. The demographic data and histories of the patients were collected retrospectively from patient files. Polymerase chain reaction-based HLA-B27 analysis of all cases was performed. Results: The male to female ratio was 2.5, and mean age of disease onset was 28.3 years. HLA-B27 positivity was detected in 115 patients (70%). Although there was no significant connection between the clinical findings and HLA-B27 positivity, there was a positive relationship between the presence of syndesmophytes and HLA-B27 positivity (p=0.044). The number of patients treated with anti-tumor necrosis factor was higher in the HLA-B27-positive group; however, the difference was not significant (39.1% and 28.9%, respectively). More patients were treated with anti-tumor necrosis factor in the HLA-B27-positive group than in the HLA-B27-negative group; however, the difference was not significant (39.1% and 28.9%, respectively). Conclusion: Compared with northern Europe, HLA-B27-positive rate of patients with AS has been shown to be lower in Turkey. Except for the presence of syndesmophytes, there was not a statistically significant relationship between HLA-B27 positivity and clinical and radiologic findings.
... Moreover, a younger age of onset, more fam- ily history [5,6], and less prevalence of psoriasis and IBD [5] have also been reported. Nevertheless, there are few studies evaluating the role of HLA-B27 in defined AS patients [7][8][9], with some of them focused on radio- graphic progression [10][11][12] and reporting controversial results [13]. The main objective of the present study was to evaluate the HLA-B27 influence on the clinical ex- pression of defined AS patients. ...
... Classically, HLA-B27 has been related to the presence of uveitis regardless of the presence or not of a definite AS [18,19]; thus, in this sense our data are unexpected. However, the results previously reported ana- lyzing the potential association between HLA-B27 in AS patients and the presence of uveitis are quite controversial [7,9,13]. It is important to note that 19.4% of HLA-B27-negative AS patients had at least one episode of uveitis. ...
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Objective: To assess HLA-B27 influence on the clinical phenotype of Ankylosing Spondylitis (AS) patients. Method: An observational, cross-sectional and descriptive study of AS patients from the Spanish REGISPONSER database was performed. Demographic, clinical, disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)), and radiographic data (Bath Ankylosing Spondylitis Radiology Index (BASRI) score) were compared regarding HLA-B27 status. A univariate and multivariate analysis was performed to identify variables independently related to the presence of HLA-B27. Results: Data from 1235 patients (74.8% male) were analyzed; 1029 were HLA-B27 positive (83%). HLA-B27-positive patients showed higher family aggregation and an earlier onset of disease compared with those who were HLA-B27 negative. HLA-B27-negative patients presented statistically higher BASDAI and BASFI scores and higher prevalence of arthritis, dactylitis, and extra-articular manifestations (psoriasis and inflammatory bowel disease (IBD)) but not anytime uveitis compared with those who were HLA-B27 positive. In the multivariate analysis, family history (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.27-3.49), younger age at diagnosis (OR 0.97, 95% CI 0.96-0.98), presence of peripheral arthritis (OR 0.53, 95% CI 0.32-0.89), dactylitis (OR 0.16, 95% CI 0.05-0.56), psoriasis (OR 0.45, 95% CI 0.26-0.78), and IBD (OR 0.22, 95% CI 0.12-0.40) were the main variables independently related to the presence or not of HLA-B27. Conclusion: In Caucasian AS patients, the presence of HLA-B27 is related to an earlier disease onset and higher family aggregation. Absence of HLA-B27 is related to a higher frequency of peripheral arthritis, dactylitis, and extra-articular manifestations. Being HLAB27 positive is not related to a higher burden of disease or anytime uveitis.
... HLA-B27 is commonly linked to the whole group of diseases and in particular to AS [28] and has been included in the clinical arm of the classification criteria of axial SpA provided by the Assessment of Spondyloarthritis International Society (ASAS) [29]. Moreover, HLA-B27 has been associated with the development of SpA-related AAU [30][31][32], which is significantly more [33]. From a pathogenic point of view, HLA-B27 is involved in the development of SpA together with a rich mixture of over 20 genes [34] and with environmental factors such as entheseal mechanical stress and gut microbiome [35,36]. ...
Article
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Spondyloarthropathies (SpA) encompass a group of chronic inflammatory diseases sharing common genetic and clinical features, including the association with HLA-B27 antigen, the involvement of both the axial and the peripheral skeleton, the presence of dactylitis, enthesitis, and typical extra-articular manifestations such as psoriasis, inflammatory bowel disease, and acute anterior uveitis (AAU). The latter is commonly reported as a noninfectious acute inflammation of the anterior uveal tract and its adjacent structures. AAU may affect more than 20% of SpA patients representing the most common extra-articular manifestation of the disease. Considering the potential consequences of untreated AAU, early diagnosis and aggressive treatment are crucial to avoid complications of remittent or chronic eye inflammation, such as visual loss and blindness. The management of SpA has dramatically improved over the last decades due to the development of new treat-to-target strategies and to the introduction of biologic disease modifying antirheumatic drugs (bDMARDs), particularly tumor necrosis factor alpha inhibitors (TNFis), currently used for the treatment of nonresponder patients to conventional synthetic agents. Along with the improvement of musculoskeletal features of SpA, bDMARDs provided an additional effect also in the management of AAU in those patients who are failures to topical and systemic conventional therapies. Nowadays, five TNFis, one interleukin-17, and one interleukin 12/23 blocker are licensed for the treatment of SpA, with different proven efficacy in preventing and treating ocular involvement. The aim of this review is to summarize the current options and to analyze the future perspectives for the management of SpA-associated AAU.
... However, we did not find an association of HLA-B27 positivity with patients with AS-associated uveitis. These results are in contrast with earlier findings indicating that HLA-B27-positive rates are significantly higher in AS patients with ANGAU that those without [28][29][30][31]. In addition, we did not a find correlation between the number of episodes of ANGAU, the clinical features of the involved eyes and the presence of antibodies to Toxocara (Table 2). ...
... However, we did not find an association of HLA-B27 positivity with patients with AS-associated uveitis. These results are in contrast with earlier findings indicating that HLA-B27-positive rates are significantly higher in AS patients with ANGAU that those without [28][29][30][31]. In addition, we did not a find correlation between the number of episodes of ANGAU, the clinical features of the involved eyes and the presence of antibodies to Toxocara (Table 2). ...
... However, we did not find an association of HLA-B27 positivity with patients with AS-associated uveitis. These results are in contrast with earlier findings indicating that HLA-B27-positive rates are significantly higher in AS patients with ANGAU that those without [28][29][30][31]. In addition, we did not a find correlation between the number of episodes of ANGAU, the clinical features of the involved eyes and the presence of antibodies to Toxocara (Table 2). ...
... Los pacientes con SpA B27 positivos presentan síntomas articulares más severos y prolongados, mayor grado de sacroileítis y espondilitis, mayor compromiso de cadera y de manifestaciones extraarticulares como uveítis anterior aguda, insuficiencia aórtica y bloqueo cardíaco que aquellos que no tienen este gen. De igual manera, los pacientes que son HLA-B27 positivos desarrollan la enfermedad a una edad más temprana y presentan una mayor tendencia familiar 10,[27][28][29] . Llama la atención la similitud de los datos obtenidos en nuestra población con los de la población mestiza mexicana y la participación de otros alelos además del HLA-B27 en las SpA y específicamente del HLA-B15 en las formas u-SpA. ...
... 9 It was also reported that HLA-B27positive AS patients are more likely to develop acute anterior uveitis than HLA-B27-negative ones as early as in 1977. 10 For the subtypes of HLA-B27, most subtypes are too rare to make any substantial statement about disease association, but the common subtypes of HLA-B27, B2702, B2704, and B2705 have all been It has been reported that HLA-B*2704-positive patients had a significantly earlier onset of disease than that of HLA-B*2705-positive patients 10 but we did not find this difference in our study. Neither were there differences in disease activity between AS patients with B*2704 and B*2705. ...
Article
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Purpose: To investigate the correlation between clinical features of ankylosing spondylitis (AS) and different human leukocyte antigen (HLA)-B27 subtypes. Methods: We conducted a cross-sectional study of 216 patients with AS. HLA-B27 and its subtypes were detected by polymerase chain reaction with sequence specific primer (PCR-SSP). Clinical features were compared between the different HLA-B27 subtypes. A meta-analysis on uveitis frequencies in AS patients with HLA-B*2705 vs 2704 was performed. Results: The most prevalent subtypes of HLA-B27 were HLA-B*2704 (66.1%) and HLA-B*2705 (32.2%). There were 57 HLA-B27-positive AS patients with the history of uveitis; 45 were B*2704 and 12 were B*2705. Patients with B*2704 had more uveitis than B*2705 (p = 0.021). After meta-analysis, there was no significant difference in the presence of uveitis between HLA-B*2704 and HLA-B*2705. Conclusions: AS patients with B*2704 have a higher risk of uveitis than AS with B*2705 in a north Chinese people.
... In order to investigate the patterns of AS, numerous studies have been performed worldwide during the past several decades. Most of these studies were based on cohorts from America [4][5][6], Europe [7][8][9][10][11], India [12], and Korea [13,14]. ...
Article
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The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P < 0.05). The clinical patterns of our AS patients were similar to those in other studies in non-Chinese cohort: (1) the age at onset was 29.2 (11.4) years, which was older than found in other studies; (2) men were more likely be HLA-B27 carriers than women; and (3) AAU was less common in Chinese patients.
... The possible correlation among different clinical manifestations and HLA-B27 status in patients with AS was identified. Indeed, some studies have reported that HLA-B27 is associated with a higher prevalence of uveitis and cardiac involvement in patients with AS. 35,36 Using regression analysis, Xiong et al 37 showed that HLA-B27 positivity was associated with worse sacroiliitis on computed tomography imaging. In addition, the large-scale study of Yang et al 23 revealed that HLA-B27(+) patients with AS have significantly more symptoms of spinal column involvement (lumbar spine and thoracic spine), hip joint involvement, and peripheral involvement than HLA-B27(−) patients with AS. ...
Article
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The association of HLA-B27 with ankylosing spondylitis (AS) remains as one of the intriguing models that could exist between a molecule and human disease in medicine. Although it was reported in 1973, its contribution to AS and related spondyloarthritis continues to be a major challenge for scientific community. It is important to understand its etiopathogenic mechanism and its functions in these diseases. Although the diagnostic and prognostic roles of HLA-B27 in AS are still debated, there is an increasing interest for HLA-B27–based effects especially in HLA-B27(+) patients with AS. This review will focus in the examination of published reports regarding the influence of HLA-B27 status on the demographic and clinical features in AS, with specific interest to its role on AS severity.
... In addition to being a pivotal part of the diagnostic work-up, a prognostic value has been attributed to HLA-B27 as well. In patients with AS HLA-B27, positivity is associated with earlier disease onset, higher disease activity, risk of peripheral joint involvement, symmetric sacroiliitis, severity of MRI findings in sacroiliitis, and positive family history [60,61,62,63], although there have been conflicting reports [64,65]. Undiagnosed patients with early inflammatory back pain-especially in case of non-radiologic axial SpA-benefit from the combination of MRI of the sacroiliac joints and HLA-B27 determination. ...
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Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.
... HLA-B27(−) AS patients, 21 although subsequent studies have shown that HLA-B27(−) patients have later age of symptom onset and diagnosis. 22 23 Therefore, taking the structural changes due to radiographic sacroiliitis as a measure of disease severity, one may extrapolate that on average HLA-B27(+) axSpA, patients have more damage than HLA-B27(−) patients in the context of familial occurrence of the disease. ...
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Objective The lifetime recurrence rate (RR) of axial spondyloarthritis (axSpA) among first-degree relatives (FDR) and the effect of proband’s gender, HLA-B27 and radiographic status is unclear. Our 35-year-follow-up family study has enabled these issues to be addressed. Methods In 1985, 363 ankylosing spondylitis (AS) probands (members of the Swiss AS Patient Society) and 806 FDR recruited into the study, completed questionnaires regarding axSpA manifestations, underwent a physical examination and most also underwent pelvic radiography and HLA-B27 typing. At follow-up in 2018–2019, of the former participants whose current addresses could be retrieved, 162 had died and 485 (125 patients with AS plus 360 FDR) completed a postal questionnaire. Results At follow-up, 48 of 177 HLA-B27(+) FDR had developed axSpA, an RR of 27.1% (95% CI 20.6% to 33.7%). 27/148 (18.2%) children of AS probands (modified New York (mNY) criteria) were affected versus 2/50 (4.0%) children of non-radiographic axSpA probands (p=0.0138, OR=5.36; 95% CI 1.23 to 23.40). Children of female probands were more often affected (12/22; 54.5%) than of male probands (15/78; 19.2%) (p=0.0003; OR=4.89; 95% CI 1.96 to 12.23). This increased risk applies equally to sons and daughters. Conclusion The lifetime RR of axSpA for HLA-B27(+) FDR is substantial (27.1%), and disease severity (as defined by radiographic sacroiliitis by the mNY criteria) is an additional risk factor. Affected mothers pass on the disease significantly more often to their offspring than do affected fathers. These findings may lead to better assessment of lifetime risk for axSpA in the offspring. Moreover, investigation of this gender effect may uncover additional putative disease susceptibility factors.
... 13 However, the prevalence of HLA-B27 in axSpA patients is found to be lower in Japan and in most Arab and Middle Eastern populations, compared to western European populations, possibly due to different genetic backgrounds. [14][15][16][17][18] The lowest figures in the region were found in Lebanon with a prevalence of 26.3% in AS, 13.8% in SpA and 1.4% in the general population, according to the latest published study in 1997. 15 These prevalence rates may affect the diagnostic value of HLA-B27 and impact the local application of published referral strategies, which are mainly elaborated in European populations with a high HLA-B27 prevalence. ...
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Aim To calculate the prevalence of human leukocyte antigen (HLA)‐B27 in axial spondyloarthritis patients (axSpA) compared to blood donors (BD) in Lebanon, to identify the clinical and radiological findings associated with HLA‐B27 and to estimate the proportion of patients fulfilling the clinical arm of the Assessment of the Spondyloarthritis International Association (ASAS) criteria. Method Consecutive Lebanese adult axSpA patients fulfilling the ASAS classification criteria were included from 12 rheumatology clinics across Lebanon. BD served as controls. A binary logistic regression was used to study the association between HLA‐B27 and the disease features. Results A total of 247 individuals were included (141 axSpA patients and 106 BD). The prevalence of HLA‐B27 was 3.8% in BD and 41.1% in axSpA. Overall, 39.7% of the axSpA patients fulfilled the clinical arm of the ASAS classification criteria. Sensitivity of HLA‐B27 for axSpA was 41.1%, specificity was 96.2%, positive predictive value was 93.6%, and negative predictive value was 55.13%. Positive likelihood ratio (LR) was 10.9 and negative LR was 1.63. We found a positive association of HLA‐B27 with family history of SpA and psoriasis. Conclusion Our study confirmed a low prevalence of HLA‐B27 in axSpA patients and BD in this Lebanese population, However, we found a high specificity and positive LR, as well as the same number of axSpA patients fulfilling the clinical arm of the ASAS criteria as in European studies. HLA‐B27 is therefore valuable for identification of axSpA in Lebanese patients despite the overall low prevalence in this population. Our results may guide future evaluations the role of HLA‐B27 in planning local referral strategies.
... The first study to compare clinical features of HLA-B27-positive versus HLA-B27negative patients with AS was that of Khan and colleagues 88 in 1977, finding no significant differences. ...
Article
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Human leukocyte antigen (HLA) B27 is the key laboratory parameter for axial spondyloarthritis (axSpA). Its prevalence is variable across different geographic zones and ethnicities, and often mirrors the prevalence of axSpA. HLA-B27 plays a role in axSpA physiopathology. It is correlated with spondyloarthritis phenotype with a consistent positive association with family history, early disease onset, shorter diagnostic delay, hip involvement, and acute anterior uveitis. HLA-B27 has a pivotal role in many referral strategies. However, these strategies were developed in European populations and need to be evaluated in populations with lower HLA-B27 background prevalence, and where additional parameters might be needed.
... Wu ve ark.'nın yaptığı çalışmada HLA-B27 ile başlangıç yası arasında ilişki saptanmazken, Khan ve ark. çalışmamızla uyumlu olarak HLA-B27 pozitif hastalarda hastalığın daha erken yaşta başladığını bildirmişlerdir [13,14]. ...
... Në literaturë raportohet shpesh, që rreth 90% e pacientëve me spondilit ankilozant (SA) nga popullatat e Evropës Veriore dhe Gjermanisë kanë HLA-B27+[328][329][330][331] ; kjo lidhje është më e dobët (deri në 80%) për artritin reaktiv (ARe), përfshi këtu sindromën Reiter, dhe spondiloartrtin (SpA), që shoqëron psoriazën (Ps) ose sëmundjen inflamatore të zorrëve (IBD)330,331 . Është raportuar gjithashtu se mosha mesatare e fillimit të sëmundjes është më e vonë në pacientët me spondiloartrit HLA-B27-neg, se në pacientët HLA-B27+ 330-336 , dhe dekursi i sëmundjes ndryshon ndërmjet këtyre dy grupeve[333][334][335][336][337][338] . Në lidhje me sakroileitin, një studim i kohëve të fundit nga Ho Yin Chung et al tregoi se ekziston lidhje ndërmjet positivitetit të HLA-B27 e gjinisë mashkullore dhe inflamacionit të artikulacioneve SI të vëzhguar në rezonancë magnetike (RM). ...
Thesis
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Background: Ankylosing spondylitis (AS) is a progressive, chronic inflammatory rheumatic disease, pertaining to the group of Spondylarthritis. This disorder affects mainly the sacroiliac joints, different regions of the vertebral column and less frequently peripheral joints and internal organs; SA is about 3 times more common in males than in females and starts usually by late adolescence or in the early years of adulthood. The severe functional limitations observed in Ankylosing spondylitis are not only the result of the predominating spinal disorders but also the result of extraspinal disease manifestations like - peripheral arthritis, cardiac and neurological involvement, inflammatory bowel disease and uveitis. Chronic pain and invalidity adversely affect the quality of life (QoL) of patients with AS. Objectives: The aim of this study was to evaluate the health related quality of life in patients with active Ankylosing Spondylitis. Methods: 110 patients were included in this cross sectional study. All patients were diagnosed with AS based upon the modified New York diagnostic criteria. Trained rheumatologists diagnosed these patients by examining them physically; reviewing theirs x-rays in order to assess the presence of sacroiliac arthritis, bamboo spine and syndesmophytes. All relevant biochemical and immunological tests were ordered and evaluated. Patients were stratified according to their BASDAI scores and those with BASDAI ≥4 were considered with active disease. Health related quality of life was measured with a generic: SF-36 and specific: ASQoL instrument. Results: There were 90 males (81.8%) and 20 females in this group (18.2%). Patients mean age was (42.23 ± 9.93) and disease duration (12.22 ±5.63). Patients with BASDAI ≥4 had a decreased health related quality of life and statistically significant changes were observed for other variables too. Conclusions: Studies show that active disease affects negatively Ankylosing Spondylitis patients quality of life. These patients should receive treatment in accordance with approved national guidelines and international recommendations; they should exercise regularly and maintain proper posture. Medical personnel should be aware of the fact that the mental and physical functioning of these patients is affected by the underlying pathology and their quality of life decreased. Patients should get information regarding all aspects of this pathology and obtain all the institutional support that they need to face this chronic and invalidating disorder.
... Ancak nüksetme olasılığı yüksek olduğundan çoğunlukla diğer gözde inflamasyon ortaya çıkmaktadır. 3,24,32,34,35 HLA-B27 pozitif olanların akut anterior üveit HLA-B27 negatif olanlara göre daha sıktır. 32 ...
Chapter
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Tanıyı homojenleştirmek amacıyla diğer birçok hastalıklarda olduğu gibi kronik bir hastalık olan Ankilozan Spondilit (AS) içinde sınıflama ve tanı kriterleri oluşturulmuştur. Genetik biliminin gelişmesiyle; AS %90 herediter kaynaklı ve AS gelişiminde HLA-B27’nin alt tiplerinin birlikte tespit edilmesi HL-B27’nin CD4+ ve T-hücreline hücre sunumu durumla genetiksel olduğu ve halen genetiksel dışı nedenler etyopatogenezde rol aldığı düşünülmektedir. Epidemiyolojik çalışmalar olmakla beraber her zaman sınıflama kriterleri tanı kriterlerinden daha yüksek spesifiteye sahiptir. AS, özellikle sakroiliak ve vertebrayla ilgili olan ve nedeni tam olarak bilinmeyen kronik, inflamatuar süreçli romatizmal bir hastalıktır. İlk bulgu sıklıkla erken yaşta başlayan mevcut tedavilere yeterli cevap vermemekle birlikte, tedavi öncesine göre Non-Steroid Anti-İnflamatuar İlaçlara (NSAİİ) iyi yanıt veren inflamatuar yapıda bel ağrısıdır. Kronik bir hastalık olarak omurgada yaptığı tutulumdan dolayı ciddi fonksiyonel bozulmalara sebep olabilmektedir. AS’de hastaların yaşam kalitesini arttırmak için birtakım tedavi yöntemleri kullanılmaktadır. Farmakolojik ve non-farmakolojik tedavi seçenekler bu yöntemlerden bazılarıdır. AS’li hastalarda medikal tedavi kadar düzenli egzersiz programlarının hazırlanıp uygulanması da son derece önemli bir yere sahiptir. Hastalara tedavi amaçlı bir takım egzersiz eğitimi verilerek mobiliteyi, kuvveti ve dayanıklılığı arttırmaya yönelik çalışmalar yapılmaktadır. Ayrıca egzersiz ile hastaların kas-iskelet bölgesinde oluşabilecek hasarların önlenmesi ve psikolojik etmenlerden faydalandırılması hedeflenmektedir. Ancak AS tedavisi üzerinde egzersizin bu kadar etkinliği ve etkisi varken reçeteleme bazında göz ardı edildiği görülmüştür. Bununla birlikte, AS’de son yıllarda yeni teknolojilerin sağlık alanında kullanıma girmesi, erken dönemde tanı konulabilmesine imkân sağlamıştır. Bu gelişmeyle daha doğru tedavi yöntemi kullanılarak morbidite-mortalitede azalmayla beraberinde yaşam kalitesinde iyileşme sağlanmaktadır. Tüm bu yeni tedavilere rağmen araştırmalar devam etmekte ancak istenen başarı seviyesine ulaşılmadığından bu konuda daha fazla bilimsel araştırmalara ihtiyaç duyulacağı görülmektedir. Buradan yola çıkarak; bu derlemenin amacı, güncel bilimsel literatüre dayanarak AS’de tedavi ve egzersiz yaklaşımlarını incelemektir.
... However, the function of HLA-B27 is not fully understood. 15 In our study, for the subgroup of patients with AS tested for HLA-B27 gene, 25 patients were HLA-B27 (+) and 10 patients were HLA-B27 (2). When we evaluated correlation between the gene status and dry eye parameters, we found only a positive correlation between HLA-B27 and OSDI scores. ...
Article
Purpose: To evaluate the clinical findings and ocular surface changes in patients with ankylosing spondylitis (AS). Methods: This prospective study involved 45 patients with AS (group 1) and 28 healthy subjects (group 2). Patients in group 1 were in the inactive period. The study subjects underwent a complete ophthalmic examination. The right eyes of the subjects in each group were tested for the study including slit-lamp examination, Schirmer I test, tear break-up time (TBUT), conjunctival impression cytology (CIC), and ocular surface disease index (OSDI). Results between the two groups were compared. Results: The mean Schirmer I test result was found as 12.2±8 mm in group 1 and 20.3±9.9 mm in group 2 (P<0.001), whereas the mean TBUT value was found as 3.8±1.9 sec in group 1 and 10.1±4.8 sec in group 2 (P<0.001). The OSDI scores were significantly higher in group 1 (36.5±19.4) than in group 2 (9.1±12.9, P<0.001). The CIC scores were significantly higher in group 1 (2.12±0.7) than in group 2 (0.57±0.6, P<0.001). Notably, none of the patients in group 1 showed grade 0 differentiation, and none of the patients in group 2 showed grade 2 or 3 differentiation. The CIC scores were significantly higher in group 1 (2.12±0.7) than in group 2 (0.57±0.6, P<0.001). Conclusion: Ocular surface changes, including squamous metaplasia in the bulbar conjunctiva, can be observed in patients with AS.
... Human leukocyte antigen-B27 (HLA B27) is one of the strongest risk factors for AS and its presence is associated with a higher prevalence of uveitis and cardiac involvement [28,29]. In this study, only one patient had evidence of uveitis and HLA B 27 positive patients had more severe disease. ...
Article
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Aim of the work To describe the clinical profile and subtypes of spondyloarthritis (SpA) patients from a tertiary care center in North-Eastern India. Patients and method This cross-sectional study was conducted from a tertiary care hospital in Northeast India including 34 patients. Diagnosis of SpA was based on the European Spondyloarthropathy Study group (ESSG) criteria. Results 34 cases were 26 (76.5%) males and 8 (23.5%) females. The male to female ratio was 3.2:1. The mean age of the patients was 45 ± 20.2 years. 21 (61.8%) belonged to the age group 21–40 years. The mean age at onset was 28.4 ± 11.4 years while the disease duration was 5.4 ± 5.1 years. Ankylosing spondylitis (AS) was the most common subtype (n = 19,56%), followed by reactive arthritis (ReA)(n = 5,15%) and undifferentiated (UdSpA)(n = 5,15%). Psoriatic arthritis (PsA)(n = 4,12%) and juvenile SpA (n = 1,3%) made up rest of the cases. The most common articular manifestations were peripheral arthritis (88.2%) followed by low back pain (73.5%) and enthesitis (50%). There was evidence of sacroiliitis in 20 (58.8%) patients of which 19 had AS and 17 (85%) were bilateral. The HLAB27 was done in 14 with AS and one with Juvenile SpA; 10(73.7%) were positive. Conclusion The commonest SpA encountered was AS with a notable male preponderance among patients. Peripheral arthritis was a common clinical presentation in all subtypes of patients. As diagnosing SpA can be challenging, it is recommended that the physicians have a high index of suspicion. Early diagnosis and knowledge of the pattern of the disease might contribute to more favorable treatment outcomes.
... However, we did not find an association of HLA-B27 positivity with patients with AS-associated uveitis. These results are in contrast with earlier findings indicating that HLA-B27-positive rates are significantly higher in AS patients with ANGAU that those without [28][29][30][31]. In addition, we did not a find correlation between the number of episodes of ANGAU, the clinical features of the involved eyes and the presence of antibodies to Toxocara (Table 2). ...
... Betrachtet man die Gesamtgruppe der Patienten mit axialer SpA inklusive der nr-ax-SpA, fällt dieser Durchschnittswert auf 60-85 % [74,192]. HLA-B27-positive Patienten mit axialer SpA haben insgesamt einen schwereren Verlauf [16,[193][194][195][196][197][198]. Kohortenstudien haben gezeigt, dass die HLA-B27-positiven Patienten früher erkranken, eine höhere Krankheitsaktivität aufweisen, an größeren funktionellen Einbußen leiden und häufiger eine Uveitis und kardiale Manifestationen entwickeln, während HLA-B27-negative Patienten später und meist weniger schwer erkranken, sie leiden aber häufiger an Psoriasis vulgaris und/ oder einer CED [193]. ...
... In this context, we focused on human leukocyte antigen B*27 (HLA-B*27), which is involved in ankylosing spondylitis (AS), an inflammatory rheumatic disease affecting the axial skeleton. 35,36 In particular, the subtype HLA-B*2705 is the ancestral allele, which has been found to be associated with AS in almost all investigated populations. Some alleles, such as HLA-B*2709, act as a non-AS-predisposing factor. ...
Article
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In this work we describe the application of the Zernike formalism to quantitatively characterize the binding pockets of two sets of biologically relevant systems. Such an approach, when applied to molecular dynamics trajectories, is able to pinpoint the subtle differences between very similar molecular regions and their impact on the local propensity to ligand binding, allowing to quantify such differences. The statistical robustness of our procedure and the comparison with experimental data both suggest that it is very suitable to describe protein binding sites and protein-ligand interactions within a rigourous and well-defined framework.
Chapter
The rheumatic diseases comprise well over 100 distinct entities affecting as many as 36 million Americans. Ankylosing spondylitis (AS) affects 3 million Americans and is third in frequency only to osteoarthritis (16 million) and rheumatoid arthritis (6.5 million)1. In England, it has been estimated that there are at least 50 000 patients with AS, a prevalence comparable to that of gout2.
Chapter
The aim of this review is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behcet’s disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.
Article
Objective To examine racial differences of clinical features, medication usage and comorbidities of ankylosing spondylitis (AS) patients in the US. Methods 28, 520 patients with AS were identified in the Explorys database. Data were stratified by two rheumatology visits, race, gender, clinical characteristics, medication use and co-morbidities. Data sets were recorded as proportions, which were compared using chisquared test (p<0.05). Results Of the 10,990 AS patients, 8% were African-Americans (AA) and had elevated ESR, CRP, high frequency of anterior uveitis, hypertension, diabetes, depression and heart disease. Conclusion AA with AS in the US have high disease activity and co-morbidities compared to Caucasians.
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Spondyloarthropathies are a cluster of Interrelated and overlapping chronic Inflammatory rheumatic diseases that primarily include ankylosing spondylitis, reactive arthritis, and the arthritis associated with psoriasis and inflammatory bowel diseases. The primary pathologic sites are the entheses (the sites of bony insertion of ligaments and tendons); the axial skeleton, including the sacroiliac joints; the limb joints; and some nonarticular structures, such as the gut skin, eye, and aortic valve. Although spondyloarthropathles are not associated with rheumatoid factor, they show a strong association with HLA-1327; however, this association varies markedly among various spondyloarthropathles and among ethnic groups. The most widely used classification criterion, from the European Spondyloarthropathy Study Group, encompasses the currently recognized wider disease spectrum, with a sensitivity and specificity that generally exceed 85%. Spondyloarthropathies occur in genetically predisposed persons and are triggered by environmental factors, but the cellular and molecular mechanisms of Inflammation are not yet fully understood. Chlamyclial and many enterobacterial infections can trigger reactive arthritis, but an infectious trigger for ankylosing spondylitis has not yet been established. HLA-1327 Itself is involved In enhancing genetic susceptibility, but the underlying molecular basis Is still unknown; additional genes include the putative susceptibility genes for Crohn disease, ulcerative colitis, and psoriasis. A specific susceptibility gene for Crohn disease, NOD2, Is located on chromosome 16q12, and one of the candidate genes for psoriasis, PSORS1, has been mapped to a 60-kb fragment on chromosome 6p, which Is telomeric to the HLA-C locus. This paper reviews the efficacy of anti-tumor necrosis factor-a therapy and other therapeutic advances.
Chapter
Spondyloarthropathies are a group of inflammatory rheumatic diseases characterized by axial and or peripheral arthritis associated with enthesitis, dactylitis, and potential extra-articular manifestations involving the eyes, heart, lung, skin, gut, and genitourinary tract. This group of diseases includes the prototypical disease ankylosing spondylitis, reactive arthritis or spondyloarthritis, psoriatic arthritis or spondyloarthritis, spondyloarthritis associated with inflammatory bowel disease, undifferentiated spondyloarthritis and juvenile-onset spondyloarthritis. The exact etiology and pathogenesis of spondyloarthropathies remain unclear, but strong evidence indicates that genetics play a major role in an individual’s susceptibility to this group of diseases, together with nongenetic environmental triggers. Studies suggest that infection can trigger spondyloarthropathies, and researchers express varying degrees of certainty about the role of infection among the subgroups of the disease. Thus, current data support the notion that infections drive the development of spondyloarthropathies, as shown in reactive arthritis. The interplay of infections, genetics, and mainly HLA-B27 contributes to the pathogenesis of this disease.
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Ankylosing Spondylitis poses significant challenges in terms of early diagnosis, assessment of disease activity, predicting response to the treatment and monitoring radiographic progression. With better understanding of underlying immunopathogenesis, effective targeted therapies are available which improve symptoms, quality of life and possibly slow the radiographic progression. There has been a growing interest in the discovery of biomarkers for defining various aspects of disease assessment and management in Ankylosing Spondylitis. The C-reactive protein and HLA-B27 are most commonly used biomarkers. This review describes many other newer biomarkers which have potential clinical applications in this chronic inflammatory disease.
Article
Although different classification criteria have been developed for psoriatic arthritis (PsA) and spondyloarthritis (SpA), a clear distinction is still not always possible in daily practice. In addition, clinical examination of patients initially diagnosed as PsA due to peripheral symptoms and skin lesions may also show inflammation in the axial skeleton causing inflammatory back pain, stiffness and changes on imaging including sacroiliitis, spondylitis and syndesmophyte formation, similar to what is known from ankylosing spondylitis (AS), the prototype of SpA. However, and in contrast to patients with AS, the long-term radiographic progression of patients with axial disease in PsA seems to be rather independent from spinal mobility. If axial symptoms predominate, diagnosis and classification can be made as axSpA - with or without psoriasis. Furthermore, also the role of HLA-B27 appears to be different in patients with PsA. Overall, the most data about axial involvement in SpA come from AS and axSpA studies, while data about the axial involvement in PsA is limited. Finally, there are no approved therapies for treatment of axial PsA at present, despite significant clinical morbidity. In recent years, anti-TNF therapies have revolutionised the management of ax-SpA. The new GRAPPA treatment recommendations have given specific management advice for patients with axial involvement based on literature from AS and axial SpA. This review aims to give an overview of the existing evidence, the clinical and imaging presentation, and therapeutic consequences of axial involvement in patients with PsA.
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Amaç: Sigara Dünya’daki en önemli önlenebilir ölüm ve sekel nedenlerindendir ve günümüze değin bir çok hastalıkla ilişkilendirilmiştir. Romatoid Artrit ve Ankilozan Spondilit hastalıkları tüm vücutta harabiyete neden olabilen ve özellikle kas-iskelet sisteminde kendisini gösteren, aynı zamanda sigara ile de ilişkilendirilmiş inflamatuar, kronik seyirli hastalıklardır. Bu çalışmada sigara bağımlılığının Romatoid Artrit ve Ankilozan Spondilit hastalarının yaşam kalitesi üzerine etkisini ölçmek amaçlanmıştır. Materyal ve metot: Çalışma Mart 2014- Temmuz 2014 tarihleri arasında Ondokuz Mayıs Üniversitesi Tıp Fakültesi Hastanesi’nde takip edilen AS ve RA tanılı hastalar üzerinde gerçekleştirilmiştir. Bu amaçla hastalarla Aile hekimliği, Göğüs hastalıkları, Fizik tedavi ve rehabilitasyon polikliniklerinde, ilgili anabilim dallarının izinleri dahilinde, yüz yüze görüşmeler yapılmıştır. Bunlar arasından sigara içenler çalışma, sigara içmeyenler ise kontrol grubu olarak kabul edilmiştir. Her iki gruba demografik bazı özellikleri içeren bir anket, SF-36, EQ-5D genel yaşam ölçeği uygulanmış ve veriler karşılaştırmalı olarak değerlendirilmiştir. Çalışma grubundaki hastalara Fagerstrom Nikotin Bağımlılık Testi uygulanarak bağımlılık dereceleri ölçülmüş ve bu sayede bağımlılık dereceleri ile yaşam kalitesi arasındaki ilişki araştırılmıştır. Toplam 145 görüşme yapılmıştır. Parametrik ve parametrik olmayan koşullara göre analizler yapılmış, istatistiksel açıdan anlamlılık düzeyi p< 0,05 olarak kabul edilmiştir. Bulgular: Olguların % 54,5’i (n= 79) RA ve % 45,5’i (n= 66) AS tanısı almışlardı. Cinsiyetleri değerlendirildiğinde ise % 54,5’i (n=79) kadın, % 45,5’i ise (n=66) erkek idi. Hastalık etyolojisi açısından cinsiyetler değerlendirildiğinde RA’lı hastaların %69,6’sı (n=55) kadın, % 30,4’ü (n=24) erkek idi. AS’li vakalarda kadınlar için %36,4 (n=24), erkekler için % 63,6 (n=42) olarak saptanmıştır. RA tanılı katılımcıların yaş ortalaması 49,65 ±12,92 yıl iken, AS tanılı katılımcılarda 39,56±12,72 yıl idi. Yapılan ölçümlere göre RA’lı hastaların VKİ’lerinin AS’li olgulardan daha fazla olduğu gözlenmiştir (t= 3,880, p<0,01). Sigara içme durumları irdelendiğinde RA hastalarının %39,2’si, AS hastalarının ise %50,0’ı sigara içmekteydi. RA’lı hastaların ortalama sigara tüketimi 17,94±14,73 paket/yıl, AS’li hastaların ortalama sigara tüketimi 13,03±9,50 paket/yıl idi ve aralarında istatistiksel olarak anlamlı bir fark yoktu. RA hastaların yaşam kalitesi skorları AS’li hastalara kıyasla SF-36 yaşam kalitesi alt grup ölçeklerinin hepsinde ve EQ-5D ölçeğinde daha düşük bulunmuştur. Sigara kullanan hastaların sigaraya başlama yaşı ile hastalık semptomları başlangıcı arasında belirgin bir korelasyon izlenememiştir (r=-0,004, p=0,953) fakat paket/yıl miktarı daha yüksek olan vakalarla erken hastalık semptomu ortaya çıkarma arasında orta düzeyde bir korelasyon vardır ( x2= 0,419, p<0,001). Sonuç: RA tanılı hastaların yaş ortalamaları AS tanılı hastalardan daha büyük idi. RA’lı hastaların VKİ’lerinin AS’li olgulardan daha fazla olduğu gözlenmiştir. Gruplar arasında ortalama sigara tüketim miktarları arasında istatistiksel olarak anlamlı bir fark yoktu. AS’li hastaların belirtilerinin RA’lı hastalardan yaklaşık olarak 10 yıl daha önce başladığı izlenmiştir. Hastalar tüm alt alanlardan istatistiksel olarak anlamlı düşük puanlar almışlardır ve AS tanılı hastalar bütün ölçek skorlamalarında RA tanılı hastalardan daha yüksek puan almışlardır. Her iki hastalıkta da sigara içenlerin VKİ değerleri daha düşük bulunmuştur. Sigara içenler arasında bağımlı olmanın SF-36 yaşam kalitesi alt grupları ve EQ-5D yaşam kalitesi skorları ile bir ilişkisi bulunamamıştır. Hastaların sigara içmeleriyle içmemelerinin yaşam kalitesine etkisini araştırdığımızda ise sigara içenlerin yaşam kalitesi puanlarının istatistiki olarak anlamsız olmakla beraber daha yüksek olduğu gözlenmiştir. Sosyo-demografik özellikler ile SF-36 ve EQ-5D arasındaki ilişkiyi analiz eden regresyon modelinde anlamlı sonuç alınmamıştır.
Article
Study of products of genes present on a region on chromosome 6 known as the Major Histocompatibility Complex (MHC) is providing new insight into many chronic diseases of undetermined aetiology, including rheumatic diseases such as ankylosing spondylitis1,2 and rheumatoid arthritis3,4. The human MHC is called HLA, and it contains a tightly linked cluster of genes that encode for cell surface glycoprotein molecules expressed on the cell membrane of virtually all cells5–7. These molecules are involved in cell-to-cell interaction and have been subdivided into two distinct groups called class I and class II molecules6–8. The class I molecules are encoded by the HLA-A, -B, and -C loci of the MHC. These molecules display an exceptional degree of genetic polymorphism and are composed of an MHC-encoded heavy — or α — chain that is non-covalently bound to β2-microglobulin, a smaller and invariant polypeptide chain encoded by a gene located on another chromosome5–8. The class II molecules consist of two glycoprotein chains as well, the larger of the two chains is called α chain and the smaller one is called β chain. These two chains are closer in size than those of the class I molecules. Moreover, both α and β chains are encoded by genes located in the HLA-D region7,8.
Chapter
Saint-Hillier et al.1 typed 7 French patients for A and B loci antigens. When compared with a control population of unknown size, they found no significant difference between the 2 groups.
Chapter
Ankylosing spondylitis (AS) is a chronic inflammatory condition of the axial skeleton and sacroiliac joints that, untreated, may progress with new bone formation to total bony ankylosis of the spinal column. The origin of the new bone in the axial skeleton occurs at the enthesis, i.e., the point of attachment of ligament to bone. This enthesitis may also occur peripherally, classically at sites such as the insertion of the Achilles tendon and of the plantar aponeurosis into the calcaneum. In addition, a proportion of cases have a seronegative, anodular inflammatory peripheral arthritis.
Article
Objective Factors predicting axial spondyloarthritis (axSpA) among first-degree relatives (FDRs) of ankylosing spondylitis (AS) patients need to be defined. We investigated the predictive value of the probands’ HLA-B27 and radiographic sacroiliitis status on disease occurrence among their FDR. We also assessed the predictive value of features of the clinical history, including chronic inflammatory back pain (CIBP) and acute anterior uveitis (AAU), among the FDR and how they can be used to improve classification and diagnosis of axSpA. Methods In 1985, we studied 363 AS probands and 806 FDR who underwent rheumatologic examination, completed questionnaires, provided blood samples for HLA-typing and underwent radiography of sacroiliac joints. At follow-up in 2018–2019, 125 patients and 360 FDR were available for study, and completed a postal questionnaire about axSpA features. FDRs were asked to report whether after 1985 they had been diagnosed by Swiss rheumatologists as having axSpA. Results Among HLA-B27(+) FDR, axSpA occurred in 25.4%–26.3%, independent of the radiographic sacroiliitis status of the proband. AAU occurred in 13/34 (38.2%) FDR with axSpA vs 29/251 (11.6%) FDR without axSpA (p = 0.00004, OR=4.74 95% CI 2.15 to 10.47). The presence of CIBP at baseline did not predict later occurrence of axSpA but combining CIBP and pain/discomfort at the thoracic spine and at anterior (ventral) chest wall ever, assessed at follow-up in 2018–2019, provided 83.1% sensitivity and 87.2% specificity for current axSpA. Conclusion Occurrence of AAU among FDR of axSpA probands should prompt screening for axSpA. Moreover, co-occurrence of CIBP and pain/discomfort in the thoracic spine and at anterior chest wall as a three-question tool may further enhance clinical suspicion of axSpA among these FDR.
Chapter
Die Spondylitis ankylosans (Sp. a.) ist ein chronisch-entzündliches Systemleiden des Bewegungsapparates mit fakultativ viszeraler Symptomatik. Sie verläuft wechselnd schnell progredient, ist dem Stand der gegenwärtigen Medizin nach unheilbar und inaktiviert sich selbst. Diese Inaktivierung kann zu jeden Zeitpunkt, d.h. in jedem Stadium der Erkrankung erfolgen. Schmerz und Funktionseinbuße am Bewegungsapparat sind die Kardinalzeichen der Sp. a.
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This chapter describes rheumatic disorders and systemic lupus erythematous (SLE). Rheumatic disorders are often chronic and disabling, ranging from joint deformity in rheumatoid arthritis to renal and central nervous system damage in SLE. These complications have particularly severe consequences in countries where medical and social services are limited or nonexistent. Nonwhite patients in developed countries often suffer socioeconomic deprivation and a chronic disease may prove an added burden. Loss of employment may occur earlier and be higher in manual workers. Education of a child with juvenile rheumatoid arthritis may be difficult anywhere but particularly in deprived populations. Access to expensive physiotherapy and rehabilitation programmes is difficult both in underdeveloped and developed countries. Understanding rheumatic disease patterns in nonwhite patients may help in diagnosis and management. Limping in an asymptomatic adolescent of African origin may suggest aseptic necrosis of the femoral head, secondary to hemoglobin SC disease. A systolic murmur in an Indian student may suggest rheumatic heart disease, and an unexplained periorbital edema in a young woman from the Caribbean may be the first sign of SLE.
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Die kongenitalen Mißbildungen der Wirbelsäule umfassen eine Vielfalt von Defekten, die schon häufig zusammenfassend dargestellt und nach verschiedenen Gesichtspunkten klassifiziert wurden. Da die Wirbelsäule ein für den Anatomen schwer zugängliches Organ ist, ist es verständlich, daß sich besonders Röntgeno-logen und Orthopäden bemüht haben, in dieser Vielfalt Ordnung zu schaffen und die kongenitalen Defekte nach Kriterien der röntgenographischen Morphologie einzuteilen. Eine ausgedehnte, kaum mehr übersehbare Literatur, darunter zahllose Publikationen von Einzelbeobachtungen liegen vor, indes Fragen nach dem Ursprung und der Entwicklung der kongenitalen Defekte bisher unsicher und ungelöst geblieben sind. Jede Beschreibung enthält zwar eine Hypothese über ihre formale und kausale Genese. Diese bleibt aber Spekulation, da bis heute nur ganz ausnahmsweise typische, immer wiederkehrende Mißbildungen in statu nascendi erfaßt wurden. Aus diesem Grunde müssen für die Erklärung ihrer Genese die Ergebnisse der experimentellen Embryologie und ganz besonders der Säugetiergenetik herangezogen werden. Diese haben in den vergangenen Jahren viel zum Verständnis beigetragen und gezeigt, daß die Wirbelsäule wie jedes andere Organ im Verlaufe der Ontogenese Phasen besonders hoher Empfindlichkeit durchläuft, die durch endogene und exogene Faktoren leicht gestört werden können.
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Normal aging is associated with changes in both arms of the immune system, namely, cell-mediated immunity and humoral immunity.1 In the former, after appropriate activation, T lymphocytes, whether helper T cells (Th), suppressor T cells (Ts), or cytotoxic T cells (TCTL), proliferate and perform their various functions; in the latter, B lymphocytes, after appropriate activation, eventually synthesize and secrete antibodies.2 The two best studied age-related changes are the diminished T-cell-dependent immune responses to foreign antigens and the increase in the incidence of autoantibodies.
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Failing immunological tolerance for critical self-antigens is the problem underlying most chronic inflammatory diseases of humans. Despite the success of novel immunosuppressive biological drugs, the so-called biologics, in the treatment of diseases such rheumatoid arthritis (RA) and type 1 diabetes, none of these approaches does lead to a permanent state of medicine free disease remission. Therefore, there is a need for therapies that restore physiological mechanisms of self-tolerance. Heat shock proteins (HSPs) have shown disease suppressive activities in many models of experimental autoimmune diseases through the induction of regulatory T cells (Tregs). Also in first clinical trials with HSP-based peptides in RA and diabetes, the induction of Tregs was noted. Due to their exceptionally high degree of evolutionary conservation, HSP protein sequences (peptides) are shared between the microbiota-associated bacterial species and the self-HSP in the tissues. Therefore, Treg mechanisms, such as those induced and maintained by gut mucosal tolerance for the microbiota, can play a role by targeting the more conserved HSP peptide sequences in the inflamed tissues. In addition, the stress upregulated presence of HSP in these tissues may well assist the targeting of the HSP induced Treg specifically to the sites of inflammation.
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When the highly increased incidence of HLA-B27 in ankylosing spondylitis was reported, this was the first striking correlation between a genetically determined allelomorphic antigenic system and a disease found in the human species, although examples of avian and murine infections had already triggered a number of less impressive investigations in other human diseases and genetic markers. The studies that followed these seminal observations soon produced evidence for an improved classification of certain inflammatory disorders with a mutual genetic background. In all these disorders, the incidence of HLA-B27 exceeds that among the symptomless individuals of the same ethnic group. For this reason, they have been called by the collective definition of B27-associated or B27-positive diseases. This chapter discusses the aetiological and pathogenetic factors and the nosological clustering in arthroreactive disorders, which, in turn, has improved diagnostic practice in rheumatology. Although the clinical usefulness of HLA typing in rheumatology is very limited, its incidental results have contributed to the understanding that MHC gene products may have other functions in addition to recognition of self and its corollaries. Thus, they may participate in the regulation of metabolic functions in nonlymphoid cells. Further research on MHC gene products and their metabolic interactions is likely to be fruitful, especially in arthro-reactive disorders triggered by known agents.
Article
The microdroplet lymphocyte cytotoxicity test was examined thoroughly in an effort to increase the reproducibility of the test. The discrepancy rate in a large series of tests was reduced from 5.16% at the start of this study to the present 0.95% by introducing certain modifications in the technique. Variables connected with the isolation of lymphocytes, handling of antisera, quality of antisera, amount of complement, incubation temperature, duration of incubation, fixing of reactions, and reading of reactions were studied. The method which has resulted appears to be reproducible, simple, and readily usable on a large scale.
Article
One hundred % of 66 patients with pelvospondylitis were found to have HL-A27, whereas the frequency of the antigen in 60 patients with sacroiliitis was 70 %. The difference in frequency of HL-A27 between the two patient groups is statistically highly significant. This implies that tissue typing could be of clinical importance for a prognostic evaluation of patients with sacroiliitis. Studies in families with several HL-NMLC identical sibs indicated a relatively low penetrance of disease in those carrying the gene for increased susceptibility to development of AS. No assocation of AS to particular MLC alleles was found either in families or in several SD-2identical AS patients.
Article
Of 189 consecutive patients seen with definite ankylosing spondylitis, 17 did not possess the transplantation antigen HLA-B27. These 17 patients had less severe radiological evidence of disease than the group as a whole, or a sub-group matched for age, sex, and duration of disease. This supports the suggestion that the HLS-B27 antigen itself may play a role in the pathogenesis of the disease, and does not serve merely as a marker for a linked immune response gene.
Article
A high association of HL–A27 specificity with ankylosing spondylitis was found in Japanese patients in spite of a very low frequency of this specificity in a normal Japanese population. These findings coincide well with those in Caucasian patients, and indicate the strong relationship between the susceptibility to ankylosing spondylitis and HL–A27 specificity beyond racial differences. No particular HL–A patterns were noted in patients with the ossification of the posterior longitudinal ligament of the cervical vertebrae. This observation provides an evidence that this disease is etiologically different from ankylosing spondylitis.
Article
In the course of histocompatibility typing in ankylosing spondylitis and Reiter's disease the B27 antigen (new terminology for W27) was found to have a lower frequency among black than among white patients. Seven patients with ankylosing spondylitis (all whites) also had Crohn's disease. There were no patients with ulcerative colitis or psoriasis. Surprisingly enough, virtually all five white B27 negative patients with ankylosing spondylitis are in the subgroup with Crohn's disease. The blacks with ankylosing spondylitis fall into two groups. Seven with severe disease, including disabling hip involvement, are positive for B27. Of eight with mild to moderate spondylitis, six are B27 negative).
Article
Using a standard microcytotoxicity technique of tissue typing, the HL-A 27 antigen was identified in 72 out of 75 patients with classical ankylosing spondylitis and in 3 out of 75 controls. The same antigen was found in 31 out of 60 first-degree relatives.
Article
The histocompatibility antigen HL-A 27 (W 27) was identified in 26 out of 50 patients with acute anterior uveitis, compared with 2 out of 50 controls. 21 patients had significant, associated diseases, and 18 of these had HL-A 27. HL-A 27 was present in 8 of the 29 patients with no associated diseases.
Article
The histocompatibility antigen HL-A 27 (W 27) was identified in 26 out of 50 patients with acute anterior uveitis, compared with 2 out of 50 controls. 21 patients had significant, associated diseases, and 18 of these had HL-A 27. HL-A 27 was present in 8 of the 29 patients with no associated diseases.
High associ-ation of an HL-A antigen, W27, with ankylosing spondy-litis Disease pre-disposition, immune responsiveness and the fine structure of the HL-A supergene
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Schlosstein L, Terasaki PI, Bluestone R, et al: High associ-ation of an HL-A antigen, W27, with ankylosing spondy-litis. N Engl J Med 288:704-706, 1973 van Rood JJ, van Hooff JP, Keuning JJ: Disease pre-disposition, immune responsiveness and the fine structure of the HL-A supergene. Transplant Rev 22:75-104, 1975
HLA B27 in blacks with ankylosing spondylitis or Reiter's disease Radiologic and scinti-scan findings in HLA-B27 negative patients with ankylos-ing spondylitis
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Low frequency of HLA-B27 in American blacks with ankylosing spondylitis
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Sausage-like toes and HLA-B27. HLA and disease
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