Absence Of HLA-B27 Research Articles

Identification of the first signs or symptoms in different spondyloarthritis subtypes and their association with HLA-B27: data from REGISPONSER and RESPONDIA registries

ObjectiveTo describe and analyse the initial symptoms attributable to patients with spondyloarthritis (SpA) and their association with HLA-B27 status.MethodsThis was an observational, cross-sectional and multicentre study with patients who fulfilled...

Эффективность и безопасность различных режимов отмены ингибиторов фактора некроза опухоли альфа при длительной ремиссии ювенильного идиопатического артрита без системных проявлений: результаты проспективного простого рандомизированного исследования

Including the tumor necrosis factor TNF inhibitors (TNFi) in the management guidelines for children with juvenile non-systemic juvenile idiopathic arthritis (JIA) has significantly increased the effectiveness of antirheumatic treatment. However, the guidelines of TNFa withdrawal when disease remission is achieved remains unclear. Objective. To study the efficacy and safety of different TNFi withdrawal regimens in patients with juvenile idiopathic arthritis without systemic manifestations due to the achievement of long-term disease remission. Patients and methods: The prospective simple randomized trial included 76 patients with JIA without non-systemic juvenile idiopathic arthritis, with a disease remission duration of ≥24 months, developed under the conditions of treatment with TNFi. Of these, 38.2% are male, the average age is 11.6 years; 67 (88.2%) patients received etanercept (0.8 mg / kg / week. subcutaneously 1 time per week), the rest – adalimumab (24 mg/m2 subcutaneously 1 time in 2 weeks). Depending on the withdrawal regimen, patients were divided into three groups: in the I group, one-time withdrawa was presented, in the II group, the interval between administrations was of two times and the III group was reduced by a dose of two times. The main indicator of the study: preservation of the stage of inactive disease / remission (according to the criteria for remission of C. Wallace) for 6, 12 and 18 months after the withdrawal of TNFi. Results. At the time of withdrawal of TNFi, the average duration of the disease was 7.3 years, the duration of therapy with TNFa was 5 years, remission – was 4.4 years. For 6, 12 and 18 months after the withdrawal of TNFi, the stage of remission persisted in 44 (57.9%), 21 (27.6%) and 18 (23.7%) patients. Exacerbation of disease was registered in 58/76 (76%) patients. Biologic therapy was resumed in 56/58 children, in all cases the stage of inactive disease was reached. Among patients with exacerbation of JIA, 23/56 (41%) continued to receive disease-modifying antirheumatic drugs. Predictors of successful withdrawal of TNFa in patients with non-systemic JIA 6 and 12 months after discontinuation of the biological therapy were the female sex, the absence of HLA B27, antinuclear factor and long-term methotrexate therapy; predictors of exacerbation - increasing in the serum concentration of calprotectin (S-100 protein), the presence of subclinical synovitis according to ultrasound and MRI of the joints and uveitis. Conclusion. After the withdrawal of TNFi, the remission stage for 6 and 12 months persisted more than in half and one third of patients. The withdrawal regimens did not affect the duration of the remission of disease. The resumption of biological therapy in the exacerbation stage of JIA made it possible to reach the remission stage in most patients. Predictors of successful withdrawal of TNFi in patients with non-systemic JIA 6 and 12 months after discontinuation of the biological therapy were the female sex, the absence of HLA B27, antinuclear factor and long-term methotrexate therapy; predictors of exacerbation – increasing in the serum concentration of calprotectin (S-100 protein), the presence of subclinical synovitis according to ultrasound and MRI of the joints and uveitis. The presence of exacerbation predictors makes it impractical the withdrawal of biological therapy due to the high risk of developing an exacerbation of disease. Key words: (TNF)-alpha inhibitors, juvenile idiopathic arthritis, long-term remission, withdrawal predictors, high-sensitivity C-reactive protein (hsCRP), serum calprotectin (S-100 protein)

Functional ERAP1 Variants Distinctively Associate with Ankylosing Spondylitis Susceptibility under the Influence of HLA-B27 in Taiwanese

Epistasis of ERAP1 single nucleotide variations (SNVs) and HLA-B27 has been linked to ankylosing spondylitis susceptibility (AS). The current study examined how prevalent ERAP1 allelic variants (SNV haplotypes) in Taiwan affect ERAP1 functions and AS susceptibility in the presence or absence of HLA-B27. Sanger sequencing was used to discover all ERAP1 coding SNVs and common allelic variants in Taiwanese full-length cDNAs from 45 human patients. For the genetic association investigation, TaqMan genotyping assays were utilized to establish the genotypes of ERAP1 SNVs in 863 AS patients and 1438 healthy controls. Ex vivo biological analysis of peripheral blood mononuclear cells from homozygous donors of two common-risk ERAP1 allelic variants was performed. Two common-risk ERAP1 allelic variants were also cloned and functionally studied. In Taiwanese, eleven frequent ERAP1 SNVs and six major ERAP1 allelic variants were discovered. We discovered that in Taiwanese, the most prevalent ERAP1-001 variant with 56E, 127R, 276I, 349M, 528K, 575D, 725R, and 730Q interacting with HLA-B27 significantly contributed to the development of AS. In HLA-B27 negative group, however, the second most prevalent ERAP1-002 variant with 56E, 127P, 276M, 349M, 528R, 575D, 725R, and 730E was substantially related with an increased risk of AS. Ex vivo and in vitro research demonstrated that ERAP1 allelic variants have a significant impact on ERAP1 functions, suggesting that ERAP1 plays a role in the development of AS. In an HLA-B27-dependent manner, common ERAP1 allelic variants are related with AS susceptibility.

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach

BackgroundJuvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce.MethodsWe conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone.ResultsA total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206).According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%).ConclusionsMore than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

Effect of Gut Involvement in Patients with High Probability of Early Spondyloarthritis: Data from the DESIR Cohort.

Inflammatory bowel disease (IBD) is a well-known extraarticular feature of spondyloarthritis (SpA). The aims of this study were to evaluate factors associated with IBD and incidence over 5 years of followup in the DESIR cohort. DESIR is a prospective observational cohort of patients with recent-onset inflammatory back pain suggestive of axial SpA. All available variables in the database were compared between patients with and without IBD at baseline and 5 years, and occurrence over 5 years of followup, with uni- and then multivariable analysis. At baseline, of 708 patients, 35 had IBD (prevalence 4.94%, CI 95% 3.3-6.5). IBD was associated (multivariable) with history of uveitis, levels of Dickkopf-1, and tumor necrosis factor, but not with phenotypic presentation (peripheral arthritis, enthesitis, dactylitis, uveitis) or baseline serum levels of other cytokines. At 5 years, 480 patients were analyzed, 58 with IBD. IBD was associated (multivariable) with fulfillment of modified New York criteria, sick leave, Bath Ankylosing Spondylitis Disease Activity Index, and smoking. There was no association with magnetic resonance imaging scores, enthesitis, psoriasis, and bone mineral density. Twenty-three incident cases of IBD were recorded: estimated occurrence rate of 0.95/100 (95% CI 0.57-1.35) patient-years (PY). Incidence of IBD is associated (multivariable) with HLA-B27 (OR 0.36, 95% CI 0.22-0.59), fulfillment of modified New York criteria (OR 3.35, 95% CI 1.85-6.08), and familial history of IBD (OR 3.31, 95% CI 1.62-6.77). In early SpA, IBD occurs with an incidence of 1/100 PY, and is associated with poor outcome, familial history of IBD, absence of HLA-B27, and fulfillment of modified New York criteria.

Peripheral Manifestations in Spondyloarthritis and their Effect: An Ancillary Analysis of the ASAS-COMOSPA Study.

To determine the factors associated with the presence of peripheral manifestations in patients with spondyloarthritis (SpA) from the Assessment in SpondyloArthritis international Society (ASAS)-COMOSPA study, and to evaluate the effect of these symptoms on treatment and patient-reported outcomes (PRO). All patients from the ASAS-COMOSPA study were included. All patients had an SpA diagnosis according to the rheumatologist. Patients and disease characteristics associated with the presence of these peripheral manifestations (peripheral arthritis, peripheral enthesitis, or dactylitis) were analyzed by univariate and multivariate logistic regression. Patients who reported peripheral manifestations were divided into 3 categories: current, history, and no history. The effect of peripheral involvement on PRO was evaluated through the use of 1-factor ANOVA. Out of the 3984 patients included in ASAS-COMOSPA, 2562 (64.3%) reported at least 1 peripheral manifestation, with a prevalence of 51.5%, 37.8%, and 15.6% for peripheral arthritis, peripheral enthesitis, and dactylitis, respectively. Being from South America, having a history of uveitis, having a current case or history of psoriasis, and the absence of HLA-B27 were associated with higher prevalence of peripheral manifestations. Patients with peripheral involvement showed greater use of drugs, and those with "current" peripheral manifestations showed higher levels in all PRO, in contrast to those with past or no history. Peripheral manifestations appear in 64% of patients with SpA. Psoriasis and the absence of HLA-B27 are associated with the development of peripheral symptoms. The presence of any peripheral symptom at the time of the visit was associated with higher scores in all PRO.

P035 Important role of HLA laboratory in the diagnosis of HLA associated diseases

A 43 years old female patient was introduced to our polyclinic and the treating physician referred her to our HLA-lab for HLA-B27 typing. According to the ordering physician the patient is suffering from back pain, stiffness in the morning, degenerative changes, facet Arthropathy and her hip was also affected, hence we were suspicious that the patient was suffering from ankylosing spondylitis. The blood pressure was normal, BMI 29, WBC 6,849/L, HB 146 g/dl, Glc 5.5 mmol/L, PTH 56.6 ng/L, anti gliedin 3.88 mg/L, CRP 3.46 mg/L. According to published studies HLA-B27 is present in 85% of patients with ankylosing spondylitis. This means that HLA-B27 positive individuals are approximately 85 times at more risk to develop ankylosing spondylitis compared to the general population. However, in this case our HLA-typing, which was performed for HLA-Class I by using SSO for low/intermediate resolution, showed a negative result for HLA-B27. The negative HLA-typing results for HLA-B27 in this female patient do not totally exclude the presence of ankylosing spondylitis because 15% of affected patients do not carry this HLA allele. However, the absence of HLA-B27 in this patient makes the diagnosis of ankylosing spondylitis unlikely. This interpretation is supported by the fact, that Ankylosing spondylitis predominantly affects male patients and not females in the age > 30 years old. In addition, the described clinical symptoms could be caused by many other various diseases. At our lab we usually performed the testing of all HLA class I alleles even when only single allele requested. In this case we have observed that the patient has beside HLA-B27 HLA-B51 also, which is very strongly associated with Behcet’s disease. Behcet’s disease has similar clinical symptoms to ankylosis spondylitis. Our positive results for HLA-B51 directed the treating physicians to perform further investigations to confirm Behcet’s disease instead of ankylosing spondylitis. The presented case highlights the important role of HLA laboratory in the diagnosis of HLA associated diseases.

A Survey on the Frequency of HLA-B27 in Patients Engaged With Seronegative Spondyloarthropathies in Kashan, Iran

Background: Seronegative Spondyloarthropathies (SNSAs) are referred to a group of diseases with same clinical and genetic features. Objectives: Due to lack of data about HLA-B27 prevalence in patient with SNSA in Kashan this study was conducted to determine the status of HLA-B27 in these patients. Patients and Methods: This cross sectional study was conducted on 294 patients suffered from SNSA. Presence or absence of HLA-B27 was checked by serological method using Greener kit. Results were analyzed with SPSS-16 software using t-test and χ 2 test. Results: Of all 26.5% of subjects were HLA-B27 positive. HLA-B27 was significantly more frequent in male patients (34.1% vs. 16.5%, P < 0.001). Prevalence of HLA-B27 was 69% in ankylosing spondylitis, 31.5% in psoriatic arthritis, 18.2% in entropathic arthropathy, 17.9% in undifferentiated spondyloarthropathies, 16.1% in reactive arthritis and 12.5% in juvenile rheumatoid arthritis (P < 0.001). Conclusions: HLA-B27 has highest prevalence in ankylosing spondylitis and least prevalence in juvenile rheumatoid arthritis. HLA-B27 prevalence was in relation with gender, type of disease, family history, peripheral, and axial joints engagement.

Temporomandibular Joint Involvement in Children with Juvenile Idiopathic Arthritis

To determine the rate of temporomandibular joint (TMJ) involvement and find factors associated with TMJ arthritis in a single-center cohort of patients with juvenile idiopathic arthritis (JIA). Retrospective analysis of all patients with JIA visiting the rheumatology clinic between January 1, 2005, and December 31, 2006. Followup information was included until August 2008. A diagnosis of TMJ arthritis was based on clinical rheumatological and/or radiological findings. After a mean followup time for JIA of 4.6 years (range 0.08-14.17), 86/223 patients (38.6%) had developed TMJ arthritis. The rate of TMJ involvement differed significantly among JIA subtypes (p = 0.0016), with 61% in extended oligoarticular, 52% in polyarticular rheumatoid factor (RF)-negative, 50% in psoriatic, 36% in systemic, 33% in polyarticular RF-positive, 33% in persistent oligoarticular, 30% in unclassified JIA, and 11% in enthesitis-related arthritis. The rate of TMJ involvement in our cohort was statistically significantly lower for patients who were HLA-B27-positive (p = 0.0002). In a multivariate analysis, the association of the following factors was confirmed: JIA subtype (p = 0.0001), a higher erythrocyte sedimentation rate (ESR) at diagnosis (p = 0.0038), involvement of joints of the upper extremity (p = 0.011), the absence of HLA-B27 (p = 0.023), and younger age at onset of JIA (p = 0.050). In our cohort of children with JIA, the overall rate of TMJ involvement was 38.6%. Patients with certain JIA subtypes, a higher ESR at disease onset, involvement of upper extremity joints, and younger age at diagnosis were more likely to develop TMJ arthritis. The presence of HLA-B27 seemed to be protective.

HLA-B*27 typing by sequence specific amplification without DNA extraction.

HLA-B27 appears to play a direct role in the pathogenesis of ankylosing spondylitis and almost all patients with this disease have HLA-B27. Therefore, a diagnosis of ankylosing spondylitis can virtually...

HLA Phenotypes and joint affection in psoriasis, acute anterior uveitis and chronic prostatitis

In a prospective study, 50 patients hospitalized for psoriasis, 34 patients hospitalized for acute anterior uveitis (AAU) and 29 patients hospitalized for chronic prostatitis, were examined. The expected increased frequencies of HLA B13 and HLA B17 in psoriasis and of HLA B27 in AAU over healthy people were found. No unsuspected association between HLA antigens was observed. Psoriatic patients with peripheral joint affection frequently had affected sacro-iliac joints and were HLA B27 negative. Joint affection was frequently seen in HLA B27 positive patients with psoriasis or AAU. In the patients with AAU, 12 out of 22 patients positive for HLA B27 exhibited radiographical sacro-iliitis. This high prevalence of sacro-iliitis suggests an interaction between genes predisposing for AAU and sacro-iliitis. Asymptomatic sacro-iliitis was found in both HLA B27 positive and negative patients. The low frequency of clinical symptoms in psoriatic sacro-iliitis could not be explained by the absence of HLA B27.