MHC studies of the primary antiphospholipid antibody syndrome and of antiphospholipid antibodies in systemic lupus erythematosus.

OBJECTIVE: To study the association of HLA Class I, II, and III alleles with antiphospholipid antibodies, both in patients with systemic lupus erythematosus (SLE) and patients with primary antiphospholipid antibody syndrome (APS).

METHODS: We studied Caucasian patients with SLE (n = 91) and with primary APS (n = 16) followed at the Ottawa General Hospital Rheumatic Disease Unit. Antiphospholipid antibodies (aPL) were defined by a positive IgG anticardiolipin antibody by serum ELISA and/or the presence of a lupus anticoagulant. HLA Class I by serology and Class II by restriction fragment length polymorphism were compared in patients with and without serum aPL, and in patients with primary APS compared to controls. C4A null alleles were studied in patients with primary APS.

RESULTS: aPL were found in 19 of 91 (21%) patients with SLE, and were associated with deep venous thrombosis in this group. In patients with primary APS, stroke, deep vein thrombosis, and recurrent fetal loss were the most common clinical features. HLA-DR17(3) and Dw24 were decreased in patients with SLE with aPL and in patients with primary APS. HLA-DR4 and the linked DR53 were significantly increased in patients with primary APS compared to patients with SLE. In patients with aPL (SLE and primary APS) compared to patients with SLE without aPL, associations were found with HLA-DR53 (p = 1.5 x 10(-4), RR 5.1), DR7 (p = 0.01, RR 5.6), and to a slightly lesser degree DQ7 (p = 0.005, RR 3.6). C4A null alleles by protein allotyping and the C4A gene deletion were not associated with primary APS.

CONCLUSION: We confirm the association of aPL with HLA Class II alleles. The strongest association with aPL in our study is with the HLA-DR53 haplotypes, some of which include the DQ7 allele, as suggested in an earlier study. The HLA-B8, DR17, DQ2 haplotype so closely associated with SLE is significantly decreased in both patients with aPL and with primary APS. C4A null alleles are not associated with primary APS in this population. Our study suggests the aPL response in SLE and primary APS is immunogenetically distinct from SLE itself.