Associations of anti-β₂-glycoprotein I autoantibodies with HLA class II alleles in three ethnic groups

Objective. To determine any HLA associations with anti-β₂- glycoprotein I (anti-β₂GPI) antibodies in a large, retrospectively studied, multiethnic group of 262 patients with primary antiphospholipid antibody syndrome (APS), systemic lupus erythematosus (SLE), or another connective tissue disease. Methods. Anti-β₂GPI antibodies were detected in sera using an enzyme-linked immunosorbent assay. HLA class II alleles (DRB1, DQA1, and DQB1) were determined by DNA oligotyping. Results. The HLA-DQB1*0302 (DQ8) allele, typically carried on HLA-DR4 haplotypes, was associated with anti- β₂GPI when compared with both anti-β₂GPI-negative SLE patients and ethnically matched normal controls, especially in Mexican Americans and, to a lesser extent, in whites. Similarly, when ethnic groups were combined, HLA- DQB1*0302, as well as HLA-DQB1*03 alleles overall (DQB1*0301,*0302, and *0303), were strongly correlated with anti-β₂GPI antibodies. The HLA-DR6 (DR13) haplotype DRB1*1302; DQB1*0604/5 was also significantly increased, primarily in blacks. HLA-DR7 was not significantly increased in any of these 3 ethnic groups, and HLA-DR53 (DRB4*0101) was increased in Mexican Americans only. Conclusion. Certain HLA class II haplotypes genetically influence the expression of antibodies to β₂GPI, an important autoimmune response in the APS, but there are variations in HLA associations among different ethnic groups.