Association and frequency of HLA-A, B and HLA-DR genes in south Tunisian patients with spondyloarthritis (SpA)

Abstract

The aim of this study is to investigate the association of HLA-A, B and HLA-DR gene expression and to assess an association of additional HLA antigens besides HLA-B27 in south Tunisian patients with spondyloarthritis (SpA). Eighty-five patients diagnosed with ankylosing spondylitis (AS, n=68) and reactive arthrithis (ReA, n=17) were selected and compared with 100 healthy controls (HC). HLA class I antigens were typed serologically using microlymphocytotoxicity technique. HLA-DRB1* alleles were studied by polymerase chain reaction amplification with sequence-specific primers. The significance of differences between patients and controls was tested by chi-square analysis. We found significantly increased frequencies of HLA-A3 (30.6%; pC=0.04; OR=2.95), HLA-B27 (62.35%; pC=4.10(-17), OR=53.55), and HLA-DRB1*15 (17.2%; pC=0.026; RR=2.58) alleles in SpA patients compared to HC. The most frequent and strongest association was observed for HLA-B27 in AS (pC=6.6 ×10(-16), OR=52.23). When AS and ReA patients were analysed separately, HLA-DRB1*15 and HLA-A3 were increased only in AS (pC=0.01, OR=2.99 and pC=0.03, OR=3.14, respectively). In ReA patients, HLA-DRB1*04 (p=0.033, pC=NS, OR=2.89) was found to be the most common allele. By analysing the HLA-B27-negative subgroup, HLA-A3 and HLA-DRB1*15 expression was found to be dependent on the presence of HLA-B27. HLA-B27 expression was higher in male (45/53; 85%) as compared to female (8/53; 15%) patients (p=0.03). Apart from HLA-B27, HLA-A3 and HLA-DRB1*15 are the MHC class I and II alleles found most frequent in Tunisian patients with AS, whereas HLA-DRB1*04 was found most frequent in ReA patients. HLA-B27 is more frequent in male than in female patients.

Frequency of HLA-Class I Allel in Patients with Spondyloarthropathy

“…Studies showed that gender differences are important in clinical findings (29,34). Consistent with the literature in this study, there are many more men than women in the B27 positive patients.…”

“…In studies, A3 was found high in HLA-B27 positive patients with SpA of the Tunis population (34). In the India population, HLA-A1 was detected low in patients (30).…”

Genetics in Ankylosing Spondylitis – Beyond HLA-B*27

“…This finding has been supported by the results obtained in different ethnic groups (Brown, et al, 1998a;Jaakkola, et al, 2006;Kchir, et al, 2010;Mahfoudh, et al, 2011;Ploski, et al, 1995;SaidNahal, et al, 2002;Sims, A M, et al, 2007). HLA-DRB1 was found to have a strong association with AS.…”

“…Two haplotypes were identified in a British case-control study: B*27positive /DRB1*07positive and B*27negative /DRB1*03positive (Sims, A M, et al, 2007). The frequency of HLA-DRB1*15 was found to be increased, in Tunisian AS patients, but this allele was in LD with B27 (Mahfoudh, et al, 2011). Within the same population, a casecontrol study reported a significant increase in HLA-DRB1*11 frequency among patients.…”

HLAB27 and HLADRB1 Genotyping of Spondyloarthropathies among Filipino Patients

“…The DRB1*0408-DQB1*0301 haplotype instead, was noted in HLA-B27-positive Finns suffering from reactive arthritis (10). In Tunisians, a higher frequency of DRB1*15 was found in AS patients, and DRB1*04 in reactive arthritis patients, as compared to healthy controls (11). On the other hand, a study by Komata et al involving HLA-B27 positive Japanese individuals suggest a linkage disequilibrium between HLA-B27*05 and DRB1*0101 indicating HLA-DRB1 alleles encoding a shared epitope associated with rheumatoid arthritis that may act as an additional susceptibility factor for developing SpA in these individuals (12).…”