Association of antiphosphatidylserine/prothrombin autoantibodies with HLA class II genes

To investigate the associations between HLA class II genes and antiphosphatidylserine/prothrombin antibodies (aPS/PT) in a group of British caucasoid patients with antiphospholipid antibodies (aPL).

This study included 82 patients with aPL. IgG aPS/PT were detected in sera using enzyme-linked immunosorbent assays. HLA-DQB1, DQA1, and DRB1 genotypes were determined by polymerase chain reaction using sequence-specific primers. All results were compared with 177 matched healthy control subjects.

IgG aPS/PT were present in 41 of 82 patients (50%). The frequencies of DQB1*0301/4, DQB1*0604/5/6/7/9, and DRB1*1302 alleles were increased in patients with aPS/PT compared with controls. To minimize the interference of the association between anti-beta2-glycoprotein I (anti-beta2GPI) and HLA, patients with anti-beta2GPI were excluded from further analyses, and only HLA-DQB1*0301/4 remained significant compared with controls (odds ratio [OR] 2.75, 95% confidence interval [95% CI] 1.2-6.5, P < 0.03). In the haplotype analysis, HLA-DQB1*0301/4;DQA1* 0301/2;DRB1*04 was significantly increased in patients with IgG aPS/PT compared with controls (OR 4.75, 95% CI 1.72-13.10, P = 0.0063).

The HLA-DQB1*0301/4;DQA1*0301/ 2;DRB1*04 haplotype and its components may influence the production of aPS/PT in the antiphospholipid syndrome, which partly explains the correlation between the lupus anticoagulant and DQB1*03.