B27 Subtypes Research Articles

Association between HLA-B*27:04 and genetic susceptibility to ankylosing spondylitis in Hunan Province.

Human leukocyte antigen (HLA) B27 is a susceptibility allele of ankylosing spondylitis (AS), and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS, but current typing methods such as sequence specific primer polymerase chain reaction (PCR-SSP) still possess limitation. Therefore, this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing (PCR-SBT). Peripheral blood of 116 patients with suspected AS (suspected AS group) and 121 healthy volunteers (control group) admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT. Among the patients in the suspected AS group, 23 patients were finally diagnosed with AS (confirmed AS group), and the remaining 93 undiagnosed patients served as the non-confirmed AS group. PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS, and the results of the 2 methods were compared. The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group [11.63% vs 2.48%; P<0.001, odds ratio (OR)=5.18, 95% confidence interval (CI) 2.097 to 12.795]. B*27:04, B*27:05, B*27:06, and B*27:07 were detected in the suspected AS group and the control group. The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group (9.48% vs 1.24%; P<0.001, OR=8.346, 95% CI 2.463 to 28.282). The positive rate of B27 in the suspected AS group and the confirmed AS group (B27+/+ and B27+/-) was significantly higher than that in the control group (χ2=16.579, P<0.001; χ2=94.582, P<0.001, respectively). Among the confirmed AS group, 21 were HLA-B27 carriers, and the B27 positive rate in the confirmed AS group was 91.3%. PCR-SBT could achieve high resolution typing of the HLA-B gene locus, with higher sensitivity, specificity, positive predictive value, negative predictive value, and accuracy than PCR-SSP. PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province. The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

HLA-B27 Subtypes Predisposing to Ankylosing Spondylitis Accumulate in an Endoplasmic Reticulum-Derived Compartment Apart From the Peptide-Loading Complex.

It was previously shown that HLA-B27 subtypes predisposing to spondyloarthritis (SpA), i.e., B*27:02, B*27:05, and B*27:07, displayed an increased propensity to form intracellular oligomers and to accumulate at a high density in cytoplasmic vesicles, as compared to the non-SpA-associated HLA-B*07:02 and HLA-B*27:06. This study was undertaken to characterize the nature and content of HLA-B-containing vesicles and to further examine their relevance to SpA predisposition. Vesicles containing HLA-B proteins were detected in transfected HeLa cells and in cells from SpA patients or HLA-B27/human β2 -microglobulin (hβ2 m)-transgenic rats, by microscopy. The nature and content of HLA-B-containing vesicles were characterized in colocalization experiments with appropriate markers. The SpA-associated HLA-B*27:04 subtype accumulated at higher levels (P < 10-5 ) in cytoplasmic vesicles compared to HLA-B*27:06, from which it differs only by 2 substitutions, reinforcing the correlation between vesicle formation and SpA predisposition. Colocalization studies showed that those vesicles contained misfolded HLA-B heavy chain along with β2 m and endoplasmic reticulum (ER) chaperones (calnexin, calreticulin, BiP, glucose-regulated protein 94-kd) and belonged to the ER but were distinct from the peptide-loading complex (PLC). Similar vesicles were observed in immune cells from HLA-B27+ SpA patients, in greater abundance than in healthy controls (P < 0.01), and in dendritic cells from HLA-B27/hβ2 m transgenic rats, correlating with SpA susceptibility. Accumulation of misfolded HLA-B heavy chain along with β2 m and ER chaperones into ER-derived vesicles distinct from the PLC is a characteristic feature of HLA-B27 subtypes predisposing to SpA. This phenomenon could contribute to HLA-B27 pathogenicity, via a noncanonical mechanism.

Distinct mechanisms survey the structural integrity of HLA-B*27:05 intracellularly and at the surface.

HLA-B*27:05 is associated with the development of autoimmune spondyloarthropathies, but the precise causal relationship between the MHC haplotype and disease pathogenesis is yet to be elucidated. Studies focusing on the structure and cellular trafficking of HLA-B*27:05 implicate several links between the onset of inflammation and the unusual conformations of the molecule inside and at the surface of antigen presenting cells. Several lines of evidence emphasize the emergence of those unnatural protein conformations under conditions where peptide loading onto B*27:05 is impaired. To understand how cellular factors distinguish between poorly loaded molecules from the optimally loaded ones, we have investigated the intracellular transport, folding, and cell surface expression of this particular B27 subtype. Our findings show that B*27:05 is structurally unstable in the absence of peptide, and that an artificially introduced disulfide bond between residues 84 and 139 conferred enhanced conformational stability to the suboptimally loaded molecules. Empty or suboptimally loaded B*27:05 can escape intracellular retention and arrive at the cell surface leading to the appearance of increased number of β2m-free heavy chains. Our study reveals a general mechanism found in the early secretory pathways of murine and human cells that apply to the quality control of MHC class I molecules, and it highlights the allotype-specific structural features of HLA-B*27:05 that can be associated with aberrant antigen presentation and that might contribute to the etiology of disease.

Polymorphisms in the F Pocket of HLA-B27 Subtypes Strongly Affect Assembly, Chaperone Interactions, and Heavy-Chain Misfolding.

HLA-B27 is associated with the inflammatory spondyloarthritides (SpA), although subtypes HLA-B*27:06 and HLA-B*27:09 are not. These subtypes differ from the HLA-B*27:05 disease-associated allele primarily at residues 114 and 116 of the heavy chain, part of the F pocket of the antigen-binding groove. Dimerization of HLA-B27 during assembly has been implicated in disease onset. The purpose of this study was to investigate the factors that influence differences in dimerization between disease-associated and non-disease-associated HLA-B27 alleles. HLA-B*27:05 and mutants resembling the HLA-B*27:06 and 09 subtypes were expressed in the rat C58 T cell line, the human CEM T cell line and its calnexin-deficient variant CEM.NKR. Immunoprecipitation, pulse-chase experiments, flow cytometry, and immunoblotting were performed to study the assembly kinetics, heavy-chain dimerization, and chaperone associations. By expressing HLA-B*27:05, 06-like, and 09 alleles on a restrictive rat transporter associated with antigen processing background, we demonstrate that a tyrosine expressed at p116, either alone or together with an aspartic acid residue at p114, inhibited HLA-B27 dimerization and increased the assembly rate. F-pocket residues altered the associations with chaperones of the early major histocompatibility complex class I folding pathway. Calnexin was demonstrated to participate in endoplasmic reticulum (ER) stress-mediated degradation of dimers, whereas the oxidoreductase ERp57 does not appear to influence dimerization. Residues within the F pocket of the peptide-binding groove, which differ between disease-associated and non-disease-associated HLA-B27 subtypes, can influence the assembly process and heavy-chain dimerization, events which have been linked to the initiation of disease pathogenesis.

Update on enthesitis-related arthritis.

This review provides a detailed update regarding the genetics, pathogenesis, disease phenotype evaluation, therapies and expected outcomes for children with enthesitis-related arthritis (ERA). Recent studies evaluated human leukocyte antigen (HLA)-B27 subtypes and non-major histocompatibility complex genes including toll like receptor 4, NLRP3, CXCR4 and PTPN12 in children with ERA. The microbiome and γδ-T cells have also been an area of active investigation. Several studies focus on the imaging phenotype of children with ERA, including the use of ultrasonography and MRI. MRI techniques studied in this population include dedicated MRI, whole-body MRI and diffusion-weighted imaging. Conventional and biologic disease-modifying agents continue to be the mainstay of therapy, though the past 2 years have witnessed several greatly needed randomized controlled trials to study the efficacy of these medications in ERA. Finally, long-term effectiveness studies of biologics in children with ERA have helped inform provider and patient expectations of disease response and prognosis. Further evaluation of the role of the microbiome and the interleukin 17/interleukin 23 axis, techniques to optimize evaluation of disease features, and efficacy and effectiveness of newer medications are greatly needed in this understudied population of children.

Aortic Regurgitation Is Common in Ankylosing Spondylitis: Time for Routine Echocardiography Evaluation?

ObjectivesThe aim of this study was to assess the prevalence of aortic regurgitation and any relation to disease activity and specific human leukocyte antigen (HLA)-B27 subtypes in patients with ankylosing spondylitis. MethodsTransthoracic echocardiography was performed in 187 patients (105 men), mean age (SD) 50 (13) years, and mean disease duration 24 (13) years, and was related to demographic, clinical, radiographic, electrocardiographic, and laboratory data. ResultsAortic regurgitation was found in 34 patients (18%; 95% confidence interval [CI], 12%-24%): mild in 24, moderate in 9, and severe in one. The prevalence was significantly higher than expected from population data. Conduction system abnormalities were documented in 25 patients (13%; 95% CI, 8%-18%), and significantly more likely in the presence of aortic regurgitation (P = .005), which was related to increasing age and longstanding disease, and increased from ∼20% in the 50s to 55% in the 70s. It was also independently associated with disease duration, with higher modified Stoke Ankylosing Spondylitis Spine Score, and with a history of anterior uveitis. HLA-B27 was present in similar proportions in the presence vs absence of aortic regurgitation. For comparison, clinically significant coronary artery disease was present in 9 patients (5%; 95% CI, 2%-8%). ConclusionPatients with ankylosing spondylitis frequently have cardiac abnormalities, but they more often consist of disease-related aortic regurgitation or conduction system abnormalities than manifestations of atherosclerotic heart disease. Because aortic regurgitation or conduction abnormalities might cause insidious symptoms not easily interpreted as of cardiac origin, we suggest that both electrocardiography and echocardiography evaluation should be part of the routine management of patients with ankylosing spondylitis.

Changes of serum levels of MMP-3, sRANKL, and OPG in juvenile-onset ankylosing spondylitis patients carrying different HLA-B27 subtypes.

Ankylosing spondylitis (AS) patients whose symptom onset occurs before 16 years of age are termed juvenile-onset ankylosing spondylitis (JAS). Investigations suggested that JAS had worse functional outcome, and abnormality of bone metabolism can appear in early stage of AS. The objectives of this study are to compare changes of serum inflammatory and bone metabolic markers and to explore the relationship between these biomarkers and disease activity in JAS with different HLA-B27 subtypes. Serum matrix metallopeptidase-3 (MMP-3), soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin (OPG) were detected by ELISA in 56, 62, and 68 JAS patients, respectively, and 32 healthy individuals were as controls. Serum MMP-3 and sRANKL were significantly higher and OPG in JAS was slightly higher than those in controls. There was no significant difference in the level of MMP-3, sRANKL, and OPG among JAS patients with B27 negativity, B*2704, B*2705, and B*2715, respectively. Serum levels of MMP-3 showed positive correlation with BASDAI and BASFI (Bath Ankylosing Spondylitis Disease Activity Index and Functional Index). Serum level of sRANKL showed positive correlation with MMP-3 and negative correlation with disease duration. The significantly higher sRANKL expression suggested the enhanced osteoclast function and imbalance of RANKL/OPG system in the inflammatory process of JAS patients carrying different B27 subtypes. It should be paid attention to the abnormality of bone metabolism during the treatment of JAS.

Clinical Features in Juvenile-Onset Ankylosing Spondylitis Patients Carrying Different B27 Subtypes.

Background. Ankylosing spondylitis (AS) is a common rheumatic disease and is characterized by inflammation of the axial skeleton. HLA-B27 is strongly associated with AS. Juvenile-onset AS (JAS) with disease onset before 16 years of age differs from adult-onset AS (AAS) in many respects. Objective. To compare the clinical features in JAS with different B27 subtypes and analyze the differences between JAS and AAS. Methods. 145 JAS and 360 AAS patients were included. The demographic data, clinical manifestations, laboratory markers, Bath AS indices, and B27 subtypes were recorded. Results. Peripheral arthritis, enthesitis, BASDAI, ESR, and CRP were significantly higher in JAS patients with HLA-B*2704 than those with B27-negative. Enthesitis and ESR were significantly higher in patients with HLA-B*2705 than those with B27-negative. The onset age of HLA-B*2715 group was much earlier than the other groups. The peripheral arthritis, enthesitis, and hip joint involvement in JAS with HLA-B*2704 were significantly higher than those in AAS with HLA-B*2704. Conclusion. JAS with different B27 subtypes had similar features in most of manifestations; JAS and AAS patients with the same subtype could have distinctive courses. Early diagnosis, hip detection, and control of systemic active inflammation in JAS patients will be helpful for improving the prognosis.

Human leukocyte antigen-B27 alleles in Xinjiang Uygur patients with ankylosing spondylitis.

We investigated the distribution of human leukocyte antigen (HLA)-B27 subtypes in Uygur ankylosing spondylitis patients in Xinjiang. B27-positive patients with ankylosing spondylitis were subtyped by using polymerase chain reaction-sequence-based typing. The HLA-B27 subtype frequencies of Uygur patients were compared with those in Han patients in Xinjiang and the other areas of China. B*2705 was the predominant subtype in Uygur patients with a frequency of 58.95%, which was much higher than that in Han patients in Xinjiang (31.58%, P < 0.05) and the other areas of China (excluding the Shandong region, which was 63.89%). The frequency of B*2704 (27.37%) in Uygur patients was the lowest and significantly lower than that in Han patients (61.18%, P < 0.05) and in 8 other areas of China. B*2710 has not been previously reported in Uygur ankylosing spondylitis patients; B*2704 was the main (61.18%) subtype in Han patients in Xinjiang, followed by B*2705 (31.58%) and was similar to the characteristics of Han patients in the other areas of China. B*2724 in Han ankylosing spondylitis patients has not been previously reported. Additionally, the B*2702/B*2705 homozygote was identified in Uygur patients. B*2702/B*2704, B*2704/B*2705, and B*2705/B*2705 homozygotes were identified in 3 Han patients. The distribution of HLAB27 subtypes in Uygur ankylosing spondylitis patients in Xinjiang significantly differed from that in Han patients. Understanding the distribution of HLAB27 subtypes in ethnic minority populations of Xinjiang is important for anthropological genetic studies and for analyzing the impact of genetic background on ankylosing spondylitis susceptibility.

HLA–B27 Subtype Oligomerization and Intracellular Accumulation Patterns Correlate With Predisposition to Spondyloarthritis

Mechanisms underlying the striking association of spondyloarthritis (SpA) with the class I major histocompatibility complex molecule HLA-B27 remain poorly understood. SpA-like disease develops spontaneously in B*2705-transgenic rats, in conjunction with high HLA-B27 expression levels. This study was undertaken to examine the effects of increased expression of HLA-B27 alleles that are differentially associated with SpA on oligomerization and intracellular redistribution. HeLa cells were transfected with complementary DNA encoding for HLA-B proteins fused to yellow fluorescent protein and/or Renilla luciferase and harvested at an early phase and a later phase of expression. We monitored HLA-B intracellular trafficking and localization by means of microscopy and live-cell imaging. Bioluminescence resonance energy transfer (BRET) and Western blotting were used to monitor HLA-B oligomerization. At low expression levels, BRET signals were similarly elevated for all SpA-associated HLA-B27 alleles tested, but were lower for the nonassociated B*2706. Of note, at higher expression levels, HLA-B27 signals remained steady while signal for HLA-B7 decreased sharply, reaching the level observed for B*2706. This was due at least in part to a decreased oligomer proportion without unfolded protein response outbreak. Such differential behavior was not abrogated by proteasome inhibition. With increased expression, all HLA-B proteins accumulated to a high density in cytoplasmic vesicles with labile form and size. The extent of this phenomenon was closely correlated with the level of association with predisposition to SpA. To our knowledge, this is the first report of a correlation between the level of predisposition to SpA conferred by HLA-B27 alleles and their biochemical behavior. These findings open new perspectives for understanding the pathogenicity of HLA-B27.

Profiling of HLA-B Alleles for Association Studies with Ankylosing Spondylitis in the Chinese Population

Human leucocyte antigen (HLA) B*27 is a susceptibility allele to ankylosing spondylitis (AS). However, major AS-associated subtypes of HLA-B*27 and other HLA-B alleles vary in different ethnic populations. Herein, we examined HLA-B alleles in a total of 360 AS patients and 350 controls of Chinese Han ancestry. The HLA-B genotyping was performed with sequence-based typing (SBT) method. Six HLA-B*27 subtypes B*27:04, B*27:05, B*27:07, B*27:08, B*27:10 and B*27:15 were observed in the cohorts. HLA-B*27:04:01 and -B*27:05:02 appeared significantly increased in AS patients, which indicated as two major susceptibility alleles to AS. Homozygous B*27 was observed only in AS patients. There are 30 HLA-B alleles identified in the studies. HLA-B*15, especially B*15:01:01:01, appeared as the major allele type in the Chinese controls. Some common HLA-B alleles such as HLA-B*15, B*13, B*46 and B*51 were significantly reduced in Chinese AS patients. In conclusion, the studies profiled the HLA-B alleles, and identified major susceptibility subtypes of B27 to AS in Han Chinese population.

Cardiac conduction system abnormalities in ankylosing spondylitis: a cross-sectional study

BackgroundCardiac conduction disturbances are common in spondyloarthropathies such as ankylosing spondylitis (AS). Whether their occurrence can be linked to signs and symptoms of rheumatic disease activity is an unsettled issue addressed in this study.MethodsIn this cross-sectional study patients with AS according to modified New York criteria but without psoriasis, inflammatory bowel disease, dementia, pregnancy, other severe diseases such as malignancy and difficulties in answering questionnaires were invited; and 210 participated (120 men), mean age 49 years (SD 13; range: 16–77). Questionnaires, physical examination, ECG, and laboratory tests were performed at the same visit.ResultsCardiac conduction disturbances were common and diagnosed in 10-33%, depending on if conservative or less conservative predefined criteria were applied. They consisted mostly of 1st degree atrio-ventricular block and prolonged QRS duration, but one patient had a pacemaker and 7 more had complete bundle branch blocks. Conduction abnormalities were associated mainly with age, male gender and body weight, and not with laboratory measures of inflammation or with Bath Ankylosing Spondylitis Disease Activity Index. Neither were they associated with the presence of HLA B27, which was found in 87% of all patients; the subtype B270502 dominated in all patients.ConclusionsCardiac conduction abnormalities are common in AS, but not associated with markers of disease activity or specific B27 subtypes. Even relatively mild conduction system abnormalities might, however, indirectly affect morbidity and mortality.

FRI0449 Higher risk of uveitis and dactylitis and older age of onset among as patients with hla-b*2705 than patients with hla-b*2704 in the chinese population

BackgroundHLA-B27 is closely associated with ankylosing spondylitis (AS), but its high polymorphism made it necessary to identify the exact correlation between HLA-B27 subtypes and AS manifestation. Several studies have attempted...

Profiling of HLA-B Alleles for Association Studies with Ankylosing Spondylitis in the Chinese Population

Human leucocyte antigen (HLA) B*27 is a susceptibility allele to ankylosing spondylitis (AS). However, major AS-associated subtypes of HLA-B*27 and other HLA-B alleles vary in different ethnic populations. Herein, we examined HLA-B alleles in a total of 360 AS patients and 350 controls of Chinese Han ancestry. The HLA-B genotyping was performed with sequence-based typing (SBT) method. Six HLA-B*27 subtypes B*27:04, B*27:05, B*27:07, B*27:08, B*27:10 and B*27:15 were observed in the cohorts. HLA-B*27:04:01 and -B*27:05:02 appeared significantly increased in AS patients, which indicated as two major susceptibility alleles to AS. Homozygous B*27 was observed only in AS patients. There are 30 HLA-B alleles identified in the studies. HLA-B*15, especially B*15:01:01:01, appeared as the major allele type in the Chinese controls. Some common HLA-B alleles such as HLA-B*15, B*13, B*46 and B*51 were significantly reduced in Chinese AS patients. In conclusion, the studies profiled the HLA-B alleles, and identified major susceptibility subtypes of B27 to AS in Han Chinese population

HLA B27 Subtype Distribution Among Patients with Ankylosing Spondylitis in Eastern Turkey

Human leukocyte antigen (HLA) B27 has a strong association with ankylosing spondylitis (AS) and other spondyloarthropathies. More than 70 subtypes of HLA B27 have been described. The present study investigated B27 subtype distribution among B27-positive patients with AS classified according to the modified New York criteria and healthy controls. Sequence-specific primer polymerase chain reaction technique was used for B27 subtyping of 43 unrelated patients with AS and 39 volunteer bone marrow donors. Among patients with AS, the male-female ratio was 6.2 and the mean age was 30 years. No relationship was found between the B27 subtypes and clinical and laboratory findings in patients with AS (p>0.05). Similarly, the frequencies of B27 subtypes did not significantly differ between patients and controls. In this study, B*2746, B*2749, and B*2767 subtypes were detected for the first time. Among B27 subtypes, the most common B27 alleles found in the patients and the controls were B*2702 and B*2705. In addition, B*2702 subtype was found predominantly in both patients (48.8%) and controls (46.2%). In conclusion, in addition to commonly encountered B*2702 and B*2705 HLA subtypes, a B*2749 subtype in a patient with AS and B*2746 as well as B*2767 subtypes in controls were determined for the first time.

Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype.

Correlation of HLA B27 subtypes with clinical features of ankylosing spondylitis

The aim of the present study was to identify the B*27 subtypes associated with ankylosing spondylitis (AS) in our population and correlate them with clinical features of AS. Whole blood samples were collected from 81 HLA-B27 positive AS patients and 29 controls (asymptomatic healthy unrelated individuals) positive for HLA-B27. Clinical details of the patients were recorded which included history of inflammatory back pain, sacroiliitis, spine involvement, enthesitis, peripheral arthritis and uveitis. HLA-B27 subtypes were detected using commercially available techniques. Fisher's exact test was used for statistical analysis. The subtypes observed in AS patients were B*2705 (67.9%, 55/81), B*2704 (28.4%, 23/81), B*2707 (2/81) and B*2702 (1/81). Subtypes in the controls were B*2705 (62.07%, 18/29), B*2707 (27.59%, 8/29) and B*2704 (10.34%, 3/29). Uveitis was observed more in B*2704-positive AS patients (34.78%, 8/23) compared to B*2705-positive AS patients (16.36%, 9/55). However, the difference was not statistically significant (P = 0.130). No major differences were found between B*2705 and B*2704 for other clinical features. B*2705 was the main subtype observed in both patient and control groups. Frequency of B*2704 was more in AS patients compared to controls. Occurrence of AS-associated uveitis was more often in B*2704-positive AS patients compared to B*2705-positive ones.

HLA-B27 subtypes in Turkish patients with ankylosing spondylitis and healthy controls

The aim of this study was to determine human leukocyte antigen (HLA)-B27 subtypes frequency in ankylosing spondylitis (AS) and related spondyloartropathy (SpA) patients. Therefore, we investigated the differences in HLA-B27 subtypes between HLA-B27-positive patients and controls. Sixty six patients were included in this study (51 AS and 15 SpA). Thirty-five individuals were diagnosed with leukemia or chronic renal failure, and their donors without any rheumatological problem (no SpA history) were selected as the control group. HLA-B27 subtyping was performed by PCR-SSP (polymerase chain reaction with sequence-specific primer) method in serologically HLA-B27-positive 46 AS patients, 9 SpA patients and control group. When the frequency of HLA-B27 was 4.5% in Turkish population, this frequency was 90.2% in AS patients. Four different HLA-B27 subtypes found in AS patients were B 2705 (65.2%), B 2702 (26.1%), B 2704 (6.5%) and B 2707 (2.2%). In SpA patients, B 2705 and B 2702 found in equal frequency. Five B27 alleles were identified in our control group: B 2705 (54.3%), B 2702 (31.4) %, B 2703 (2.9%), B 2704 (2.9%) and B 2702/B 2705 (8.5%). Both in the patient group and in the control group, we also observed B 2705 as most frequent allele, and B 2702 was second common allele. Our results show that the frequency of HLA-B27 subtypes is not significantly different between patients and controls (P > 0.10).

The Role of HLA-B27 in Spondyloarthritis

This article summarizes the proceedings of a one-day international workshop held in July 2009 on the role of HLA-B27 in the pathogenesis of ankylosing spondylitis (AS) and related disorders. HLA-B27 is found in about 90% of patients with AS, with an odds ratio of about 100, but the mechanism underlying this association is not known. There are currently 3 major mechanistic hypotheses for this association: (1) T cell recognition of one or more B27 presented peptides; (2) B27 heavy-chain misfolding that induces an unfolded protein response; and (3) innate immune recognition of cell-surface expressed B27 heavy-chain dimers. None of these hypotheses accounts for the tissue specificity of the inflammation characteristic of AS. These hypotheses were discussed in the context of known epidemiologic, biochemical, structural, and immunologic differences among HLA-B27 subtypes; data from the HLA-B27 transgenic rat model of spondyloarthritis; the growing list of other genes that have been found to be associated with AS; and other data on the pathogenesis of spondyloarthritis. Proposed directions for future research include expanded efforts to define similarities and differences among the B27 subtypes; further development of animal models; identifying the interactions of B27 with the products of other genes associated with AS; and continued investigation into the pathogenesis of spondyloarthritis.

HLA-B27: what's new?

The HLA-B27 molecule is one of the most fascinating in medicine. Its contribution to the aetiopathogenesis of SpA and other diseases, and its protective action in certain infections, continue to challenge our understanding of its immunobiology and physiological roles. Animal studies have helped to cast light on ways in which HLA-B27 exerts its effects. Subtle variations in structure and behaviour between B27 subtypes that are strongly associated with SpA, compared with those whose association is neutral or weak, are helping to elucidate its pathogenetic mechanisms. However, none of the current hypotheses fully explains the observed actions of HLA-B27. Consequently, attention is turning to how haplotype linkages and genetic networks involving other MHC and non-MHC genes influence the penetrance and clinical expression of B27. HLA-B27 gives an intriguing insight into the connection between heredity and disease. As well as its close links with SpA, various other associations have been reported between B27 and diseases of different organs and systems. Evidence is also accumulating that it mitigates the virulence of HIV and other viral infections. The role of HLA-B27 as an aid to diagnosis, prognosis and disease management is gradually becoming clearer.