HLA-B27-derived peptides as autoantigens for T lymphocytes in ankylosing spondylitis

Objective.To study whether peptides derived from the HLA-B27 molecule sequence can stimulate peripheral blood T lymphocytes (PBL) from patients with HLA-B27-associated spondylarthropathies. Methods.PBL from 55 HLA-B27+ patients with ankylosing spondylitis (AS), 28 HLA-B27+ patients with other spondylarthropathies, 7 rheumatoid arthritis patients, and 30 HLA-B27+ and 22 HLA-B27- healthy controls were tested in lymphocyte proliferation assays with 4 synthetic peptides derived from the HLA-B*2705 molecule. Results. A 13-mer peptide (B27PA) induced significant proliferative responses in 17 of the 55 AS patients (stimulation index [SI] 2.5–17.5), as well as in 3 of the HLA-B27+ healthy controls (SI 2.5–9.8). Another 13-mer peptide (B27PC) induced PBL proliferation (SI 2.7–5.5) in 10 AS patients and in some donors of the control groups. In B27PA-specific T cell lines, an expansion of cells positive for the γ/δ T cell receptor could be demonstrated. Conclusion. These results indicate that HLA-B27-derived peptides can be recognized as autoantigens by PBL of HLA-B27+ AS patients and B27+ healthy controls. Recent infections preceding the manifestation of AS may be involved in this process of anti-self major histocompatibility complex reactivity.     

Occurrence of ankylosing spondylitis in a nationwide series of twins

Objective. To obtain information on the rate of concordance for ankylosing spondylitis (AS) in a population-based series of twins. Methods. AS cases were identified by record linkage of the population-based Finnish Twin Cohort and the nationwide registry for fully reimbursed medications. A clinical examination was performed to establish concordance for AS. Results. There were 6 monozygotic (MZ) pairs and 20 dizygotic (DZ) pairs with at least 1 member affected by AS. Three MZ pairs and 3 DZ pairs were concordant for the disease. All affected subjects were HLA-B27 positive. The pairwise concordance rate was 50% in MZ twins and 20% in HLA-B27 positive DZ twins (95% confidence intervals 11.8–88.2% and 4.3%–48.1%, respectively). Conclusion. These results indicate that AS disease expression is largely, but not entirely, genetically based, with a gene or genes other than B27 probably playing a role.     

Distribution of HLA-B27 and its alleles in patients with reactive arthritis and with ankylosing spondylitis in Tunisia

The purpose of the present study is to investigate the frequency of HLA-B27 and its alleles in reactive arthritis (ReA) and in ankylosing spondylitis (AS) in Tunisia. HLA-B27 alleles were typed by PCR amplification with sequence-specific primers. We studied 17 patients with ReA associated with urethritis or with gastrointestinal infection; 42 HLA-B27-positive patients with AS and 100 healthy controls. Eleven ReA patients (67.7%) were HLA-B27 positive. There was an increased frequencies of HLA-B27 (P = 7.76 × 10⁻¹², OR = 59.30) and a moderate increase of HLA-B51 (P = 0.015; OR = 4.91) alleles in ReA patients when compared with healthy controls. Four B27 subtypes were identified: B*2702, 05, 09 and B*2712. The distribution of these alleles in the ReA patients was 37.5% for B*2702 and B*2705. Only these two subtypes were detected in 18 (42.8%) and 24 (57.1%), respectively, of the AS patients. B*2709 and B*2712 were relatively rare in ReA patients and were identified in one case each. Our results showed a restricted number of HLA-B27 subtypes associated with ReA and AS. B*2702 and 2705 were common in ReA and AS patients.     

Frequency of HLA-B27 and its alleles in patients with Reiter syndrome: comparison with the frequency in other spondyloarthropathies and a healthy control population

This retrospective study analyzed the HLA-B 27 alleles in a group of 20 consecutive patients with the diagnosis of Reiter syndrome (RS) followed in a tertiary referral university hospital in Brazil, during the period 1990-2006, and compared the data with that observed in other patients with spondyloarthropathies followed at the same institution. Eight cases were associated to gastrointestinal infection, eight cases to previous urethritis, and four cases presented no established preceding infection. HLA-B 27 alleles were typed by polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes (HLA-B 2,701 to HLA-B 2,721). They were compared to a group of 108 patients with ankylosing spondylitis (AS), 40 with undifferentiated spondyloarthropathy (uSpA) and 111 healthy controls. Among the 20 patients, 17 were HLA-B 27 positive (85%). Two HLA-B 27 alleles were observed: HLA-B 2,705 (65%) and HLA-B 2,702 (35%). In the other spondyloarthropathies, the observed alleles were HLA-B 2,705 (90% in AS and 92.5% in uSpA), HLA-B 2,702 (8% in AS and 5% in uSpA), HLA-B 2,704 (1% in AS and 2.5% in uSpA) and HLA-B 2,713 (1% in AS). Among the 111 healthy controls, 80% presented HLA-B 2,705, followed by HLA-B 2,702 in 10%, HLA-B 2,703 in 6%, HLA-B 2,707 in 3% and HLA-B 2,713 in 1%. Concluding, in the HLA-B 27 positive patients with RS in this study there was predominance of HLA-B 2,705 allele, in a lower frequency than that observed in patients with other spondyloarthropathies and healthy controls.     

Susceptibility to ankylosing spondylitis in twins the role of genes,HLA, and the environment

Objective. To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS). Methods. Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence-specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS. Results. Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co-twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance. Conclusion. Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.     

High frequencies of HLA-B27 in Chinese patients with suspected of ankylosing spondylitis

This study was performed to investigate the frequency of human leukocyte antigen (HLA)-B27 in Chinese patients with suspected of ankylosing spondylitis (AS) and to assess the clinical significance of HLA-B27 typing. A total of 1,016 patients suspected of AS were classified into six groups based on one major AS-related clinical manifestation. HLA-B27 was determined by polymerase chain reaction using sequence-specific primers. The frequency of B27 ranged between 24.3 and 46.7% among the patient groups, significantly higher than in healthy controls (2.4%). In the same group, the frequency of B27 in young (≤40 years) and in male patients was significantly higher than in the old and in female (P < 0.01). During a 1-year follow-up, 102 subjects were definitely diagnosed as AS, but only one B27(−) patient. Of the 102 definite patients, 69 (67.6%) definite patients were distributed in group 1 (low back pain and stiffness) with the higher incidence (28.5%) of AS. The incidence of AS in the same group was found with a similar pattern to the frequency of B27, in male and young patients significantly greater, except groups 4 and 6 (peripheral arthritis and alteration of skin). These findings confirm that HLA-B27 is one of sensitive diagnostic tools for early AS and suggest that there was a remarkable clinical significance of HLA-B27 typing in Chinese patients suspected of AS, particularly a young man who presents with low back pain and stiffness for >3 months.     

Association of hla-b39 with hla-b27-negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in japanese patients

Objective. To investigate the characteristics of HLA-B27 that render susceptibility to seronegative spondylarthropathies. Methods. Serologic HLA class I typing of Japanese patients with ankylosing spondylitis (AS), juvenile rheumatoid arthritis (JRA), and healthy controls, was performed. HLA-B39 subtypes were determined by polymerase chain reaction-sequence-specific oligohy-bridization. Results. HLA-B27 was present in 40 of 48 patients with AS (83%), and in only 1 of 210 healthy controls (0.5%). Three of 8 patients (37.5%) who were negative for HLA-B27 were positive for HLA-B39, which was significantly higher compared with the HLA-B27-negative controls (6.2% P = 0.01). Significant association with HLA-B39 was also noted in the JRA patients (16.7%; P < 0.01), especially in those patients with pauciarticular-onset disease (33.3%; P < 0.01). Ten of 13 HLA-B39-positive patients had subtype B^*3901 and 3 had B^*3902. Conclusion. Because HLA-B27 and HLA-B39 share Glu at position 45 and Cys at position 67, both of which constitute components of the peptide-anchoring B pocket, and because they possess similar peptide-ligand motifs, our results may support either the role of the peptides presented by class I antigens or the importance of Cys at position 67, in the development of spondylarthropathies and pauciarticular-onset JRA.     

Role of enteric Klebsiella pneumonia infection and HLA-B27 in ankylosing spondylitis]

Klebsiella pneumonia (KP) infection and HLA-B 27 have been shown to be strongly associated with ankylosing spondylitis (AS). In the present study, faecal cultures were performed and showed faecal carriage rate of KP was much higher in patients with AS (10/30) and hospital volunteers (2/10) than in the non-hospital volunteers (0/20). An octadecapeptide encompassing the shared hexamer between HLA-B 27 and KP nitrogenase residue was synthesized and autoantibodies against this short peptide were detected in sera of patients with AS and Reiter's syndrome (RS) and other related disease and normal controls. The results showed that such autoantibodies were detected in 42.2% of AS and 30% of RS patients yielding positive rate much higher than those found in other control groups. It is concluded that enteric KP infection were strongly implicated in the pathogenesis of AS probably by the mechanism of molecular mimicry with HLA-B 27.     

Characterization and outcome of uveitis in 350 patients with spondyloarthropathies

This retrospective study analyzed 350 patients with the diagnosis of spondyloarthropathies (SPA) (207 with ankylosing spondylitis (AS), 80 with undifferentiated spondyloarthropathies (USPA) and 63 with psoriatic arthritis (PsA)) attended at a tertiary referral hospital for a minimum period of 5 years. All the patients presented complete clinical (axial and peripheral involvement, heel enthesopathies, extra-articular manifestations) and radiologic (sacroiliac, lumbar, dorsal and cervical spine) evaluation. HLA-B27 and respective alleles were searched. These data were compared with the occurrence of uveitis during the follow-up of the SPA patients. Thirty AS patients (14.5%) presented 55 episodes of acute anterior uveitis; there was statistical association between uveitis and juvenile-onset AS (P = 0.0094) and achillean (P = 0.0003) and plantar (P = 0.0067) enthesopathies; one AS patient presented a single episode of posterior uveitis, associated to tuberculosis. Seven USPA patients (8.8%) presented 13 episodes of acute anterior uveitis; it was not observed statistical association with any variable; one patient presented a single episode of posterior uveitis, associated to toxoplasmosis. Five HLA-B27 positive PsA patients (8%) presented 13 episodes of acute anterior uveitis. All the 26 positive HLA-B27 SPA patients with anterior uveitis tested for the HLA-B27 alleles were HLA-B*2705. No patient presented ophthalmologic severe sequelae of the anterior uveitis. Concluding, anterior uveitis was associated to the juvenile onset of the disease and to the enthesophatic involvement of the lower limbs in AS patients. The HLA-B*2705 allele was predominant in the anterior uveitis patients, whilst posterior uveitis was rare and associated to infectious disease.     

Recent studies on the genetic basis of ankylosing spondylitis

Recent studies published on the genetic basis of ankylosing spondylitis (AS) reflect novel areas of investigation and extension of recent advances. As HLA-B27 subtypes have been extensively examined in other ethnic groups, novel insights into the relevance of HLA-B27 folding to disease susceptibility have led to questions regarding the influence of HLA-B27 on AS pathogenesis. The recent identification of IL23R, ERAP1, and interleukin-1 (IL1A) region genes in AS pathogenesis has led to a number of replication studies. Other genes with inconsistent AS associations (eg, KIR, TLR4, ANKH, and TNAP) have been further examined with inconsistent results. Potential candidate genes (TIRAP, COL1A6, and MEFV) have been examined with no associations found. Tremendous progress has been made with respect to understanding the genetic basis of AS. The identification of new genes—ARTS1, IL23R, and IL1A—substantiate that susceptibility to AS is also determined by genes outside the MHC.     

Pattern of ankylosing spondylitis in an Iranian population of 98 patients

The prevalence and pattern of ankylosing spondylitis (AS) can vary from country to country, according to genetic and environmental factors. This study aims to analyze the patterns of disease in a population of Iranian patients with AS. We performed a prospective study (2002–2007) analyzing 98 patients with diagnosis of AS according to the modified New York criteria. Selected patients underwent complete clinical (initial symptom, axial and peripheral involvement, heel enthesitis, extra-articular manifestations) and radiological (sacroiliac, lumbar, thoracic, and cervical spine) investigations, and these data were compared with sex, age at onset, and HLA-B27. There was predominance of men (71.4%), adult onset (>16 years, 90.8%), and positive HLA-B27 (73.4%). Family history of AS was noted in 14.3% of the patients. The predominant initial symptoms were inflammatory low back pain (44.2%). Radiological findings included syndesmophytes in 34.7% and “bamboo spine” in 16.3% of patients. Acute anterior uveitis was noted in 44.9% of patients. Male sex was associated with involvement of shoulder (P = 0.001). Female sex and juvenile-onset AS were associated with extra-articular involvement. Positive HLA-B27 was associated with hip involvement (P = 0.042) and adult-onset AS (P = 0.035). Analysis of the patterns of disease in this population of 98 southern Iranian patients with AS revealed that female sex and juvenile-onset AS were associated with extensive extra-axial involvement; and HLA-B27 was associated with hip involvement. The study was conducted in Rheumatology Clinic of Hafez Hospital of Shiraz University of Medical Sciences, Shiraz, Iran.     

Ankylosing spondylitis and HLA-B27: restriction fragment length polymorphism and sequencing of an HLA-B27 allele from a patient with ankylosing spondylitis.

Two groups of patients with ankylosing spondylitis (AS) from England and Poland were examined for restriction fragment length polymorphisms (RFLPs) associated with the disease. No preferential association was found between the 9.2 kb PvuII fragment in HLA-B27 positive patients with AS compared with HLA-B27 healthy subjects as had been previously reported. In the English group, however, a 14 kb PvuII fragment was more common in HLA-B27 positive subjects with AS than in normal controls. Also 4.6 and 3.7 kb PvuII fragments were more prevalent in subjects without AS than in the group with AS, but these results were confined to the English group. Furthermore, the sequence of an HLA-B*2705 gene isolated from a patient with AS was examined, and no significant differences were found compared with the sequence isolated from a healthy subject. There do not seem to be significant genetic differences in the coding or in the regulatory region in HLA-B27 alleles, in subjects with or without AS.     

Clinical features of ankylosing spondylitis may correlate with HLA-B27 polymorphism

The objective of this study is to investigate the relationship between clinical features of ankylosing spondylitis (AS) and HLA-B27 status or its subtypes. Clinical data and blood samples were collected with patients’ informed consent. Luminex liquid array combining polymerase chain reaction-sequence specific oligonucleotide probe was used to do the low-resolution HLA-B genotype typing. Polymerase chain reaction-sequence specific primer was applied to do the high resolution HLA-B27 typing. In 98 subjects, 93 were HLA-B27 positive, of which three subtypes were detected: B*2704 (n = 76), B*2705 (n = 12), and B*2715 (n = 5). The onset age for B27 negative and positive group was 28 ± 7.9 and 21.1 ± 6.2 years, respectively (χ² = −2.047, P = 0.041). The onset age for B*2704, B*2705 and B*2715 group was 20.45 ± 4.50, 26.67 ± 9.95 and 17.8 ± 11.12 years, respectively (χ² = 7.888, P = 0.019). No significant difference was found between B27 positive and negative group, or among three B27 subtypes groups for other clinical features. In conclusion, the clinical features of AS may be correlated with HLA-B27 status and its polymorphism.     

Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism

OBJECTIVE: To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon gamma (IFNgamma), interleukin 4 (IL4), tumour necrosis factor alpha (TNFalpha), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls. METHODS: Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFNgamma, TNFalpha, IL4, and IL10, and analysed by flow cytometry. TNFalpha production was related to the genotype of the TNFalpha promoter at the -308 and -238 polymorphisms. RESULTS: In peripheral blood the percentage of TNFalpha+ T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNFalpha+ T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFNgamma+ T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNFalpha+ T cells than TNF1/1 homozygosity (n=25; median 9.97% v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/phenotype correlation (median 9.4% v 10.6%). CONCLUSIONS: The lower T cell production of TNFalpha and IFNgamma shown at the single cell level in HLA-B27 positive patients with AS and healthy HLA-B27 positive controls may contribute to the increased susceptibility of HLA-B27 positive subjects to develop AS. Preliminary genotype-phenotype correlations suggest that in HLA-B27 positive subjects TNF2 at -308 or a linked gene results in higher TNFalpha production and, therefore, might be a marker for a protective haplotype.     

Two distinctive HLA haplotypes harbor the B27 alleles negatively or positively associated with ankylosing spondylitis in Sardinia: implications for disease pathogenesis

OBJECTIVE: To compare haplotype distribution in HLA-B27-positive patients with ankylosing spondylitis (AS) and healthy control subjects possessing either AS-associated HLA-B27 alleles or the non-AS-associated HLA-B*2709 allele. METHODS: DNA samples from 47 HLA-B27-positive patients with AS and 76 HLA-B27-positive healthy controls (19 positive and 57 negative for B*2709) living in different areas of Sardinia were collected and typed for HLA class I and class II alleles. The third exon of the B27 gene was analyzed for the presence of Asp(116) or His(116), which differentiates B*2709 from the other two B27 subtypes (B*2705 and B*2702) that are mostly found in Sardinia. The parents of 6 subjects positive for B*2709 were also typed for HLA class I and class II alleles. Statistical analysis was performed by Fisher's exact test. RESULTS: In Sardinia, the B27 alleles conferring susceptibility to AS appear to be more frequently carried by a haplotype (A2;B27;Cw2;DR16) that reaches its highest frequency in patients with AS (A2 80.8%, B27 100%, Cw2 83%, and DR16 74.5%). Conversely, the non-AS-associated B*2709 allele is more frequently found together with other HLA alleles whose frequencies are inversely correlated with the disease (A32 or A30, Cw1, and DR12). Familial analysis of 6 subjects positive for HLA-B*2709 confirmed the existence of a "Sardinian" haplotype that is not associated with AS (A32;B*2709;Cw1;DR12). CONCLUSION: In Sardinia, 2 distinct haplotypes harbor the non-AS-associated HLA-B*2709 allele or the AS-associated B27 alleles. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 may play some role in conferring susceptibility to AS.     

Prevalence of hepatitis B surface antigen in patients with ankylosing spondylitis and its association with HLA-B27: a retrospective study from south China

To investigate the prevalence of hepatitis B surface antigen (HBsAg), a seromarker for current infection of hepatitis B virus, in patients with ankylosing spondylitis (AS) from south China and to evaluate its association with human leukocyte antigen (HLA)-B27. The prevalence of HBsAg was retrospectively investigated in 439 patients with AS, 606 age- and sex-matched general individuals, 172 patients with other spondyloarthropathy (SpA), 698 patients with rheumatoid arthritis (RA), and 220 patients with osteoarthritis (OA). The positive rate of HBsAg in AS group was compared with those of the general population group and other disease groups, respectively, and the prevalence of HBsAg was compared between HLA-B27-positive and HLA-B27-negative patients with AS. The positive rate of HBsAg in AS patients, general population, other-SpA, RA, and OA patients were 25.39, 12.87, 14.53, 9.60, and 8.18%, respectively. The HBsAg prevalence of AS group was statistically higher than those of any other groups (P?<?0.05). The prevalence of HBsAg in HLA-B27-positive and HLA-B27-negative AS patients were 26.68 and 14.49%, respectively, the positive rate of HBsAg in HLA-B27-positive AS patients was statistically higher than that of HLA-B27-negative AS patients (P?<?0.05). The prevalence of HBsAg in AS patients was higher than those in general population, patients with other-SpA, RA, and OA. The high HBsAg prevalence in AS patients might be associated with their high frequency of HLA-B27 gene.     

中国汉族强直性脊柱炎患者人类白细胞抗原-B27多态性研究

目的 本研究拟利用最新的人类白细胞抗原(HLA)-B27亚型数据,调查中国汉族强直性脊柱炎(AS)患者HLA-B27及其亚型的分布情况.方法 从我院脊柱关节炎患者数据库中随机抽取100例AS患者.用luminex液态芯片,结合聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)技术对HLA-B位点作低分辨分型.HLA-B27阳性者进一步用聚合酶链反应-序列特异性引物(PCR-SSP)法做高分辨HLA-B27亚型检测.结果 经随机抽样纳入无关AS患者98例,其中HLA-B27阳性93例,阳性率94.9%,其中B*2704亚型76例(81.7%),B*2705亚型12例(12.9%),B*2715亚型5例(5.4%).与另外2篇文献报道的HLA-B27阳性汉族健康人群比较,没有一致的证据表明HLA-B27亚型分布在AS患者和健康人群中存在差异.但这2项汉族健康人群中的研究均未发现B*2715亚型.结论 中国汉族AS患者B27亚型以B*2704为主,其次是B*2705.B*2715作为一个频率极低的等位基因,本组病例中发现5例,提示B*2715与AS发病存在关联.     

Reiter's syndrome — A comparative study of patients with the complete and the incomplete syndrome

Summary Eighty patients with Reiter's syndrome (RS) were studied retrospectively. A comparison was made between patients with the complete syndrome and patients with the incomplete syndrome. A comparison was also made between patients with and without HLA-B27. There were no major differences in severity and duration of the arthritic symptoms or in mucocutaneous involvement between the complete and incomplete groups, which indicates that they, in fact, represent the same disease. Most of the patients with sacroiliac joint involvement belonged to the HLA-B27positive group; otherwise there was no difference in arthritic symptoms between the HLA-B27positive and the HLA-B27 negative group.     

Association between KIR polymorphisms and ankylosing spondylitis in populations: A meta-analysis

Abstract

Objectives. Published association studies of killer cell immunoglobulin-like receptors (KIRs) and ankylosing spondylitis (AS) in populations are inconsistent. The aim of this study is to determine whether the KIR polymorphisms confer susceptibility to AS in populations by conducting a meta-analysis.

Methods. A computer search was carried out up to August 2013 for literature pertaining to AS and KIR polymorphisms. Publications addressing the association between the KIR polymorphisms and susceptibility to AS in populations were selected from the Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM) databases. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated.

Results. A total of 13 case-control studies in 9 articles were included in this meta-analysis. Meta-analysis results identified two positive associations of 2DS4 and 3DS1 with susceptibility to AS in populations. In subgroup analysis, there was a positive association between 2DS4 and susceptibility to AS in Asians, but not in Caucasians. And there were associations between 3DL1, 3DS1 and susceptibility to AS in Caucasians, but not in Asians. Results of subgroup analysis also showed that there were associations between 2DL5, 2DS4, 2DS5, 3DL1, 3DS1 and susceptibility to AS in HLA-B*27-positive patients and HLA-B*27-positive healthy controls.

Conclusions. This meta-analysis confirms that 2DS4 and 3DS1 might be potential risk factors for AS in populations.     

Association of sister chromatid exchange frequencies in patients with ankylosing spondylitis with and without HLA-B27

BACKGROUND: The analysis of sister chromatid exchange (SCE) is a cytogenetic technique used to show DNA damage due to an exchange of DNA fragments between sister chromatids. OBJECTIVE: To determine whether HLA-B27 positive patients with ankylosing spondylitis (AS) were associated with higher SCE frequencies than patients without B27. METHODS: Lymphocytes from 38 patients with AS (15 women, 23 men) and 34 control subjects were examined. Peripheral lymphocytes were cultured in darkness for 72 hours in BrdU added culture. Metaphase chromosomes were stained with a fluorescence and a Giemsa stain after a standard harvest procedure. RESULTS: The frequency of SCE was significantly increased in patients with AS compared with controls (p<0.001). Furthermore, the SCE frequencies in patients with positive HLA-B27 was much higher than in patients with negative HLA-B27 (p<0.001). The difference between SCE frequencies in the control groups with and without HLA-B27 was not significant. CONCLUSION: There is a strong association between HLA-B27 and the frequencies of SCE in patients with AS.