Relationship of anticardiolipin antibodies and antiphospholipid syndrome to HLA-DR7 in Mexican patients with systemic lupus erythematosus (SLE).

Abstract

We studied IgG and IgM anticardiolipin antibodies (aCL) by an ELISA method in 80 Mexican systemic lupus erythematosus (SLE) patients and 378 of their first degree relatives. Sixty five percent of SLE patients and 16% of their relatives were positive for aCL. We also determined allele and haplotype frequencies of Major Histocompatibility Complex (MHC) genes (classes I, II and III) in both patients and relatives. MHC allele and haplotype frequencies of aCL positive and negative individuals were compared to those of normal ethnically matched controls. SLE patients with aCL had statistically significant increased corrected frequencies of HLA-DR3 (pC = 0.04, RR = 2.78); DR7 (pC = 0.005), RR = 3.42) and DQ2 (pC = 0.003, RR = 2.58) antigens. Their first degree relatives positive for aCL also had increased frequency of HLA-DR7 but it did not remain significant after correcting the P value. On the other hand, SLE patients negative for aCL had a moderate increased frequency of DR3 and DQ2 but not of DR7. These results suggest that DR7 associates with the presence of aCL. The distribution of MHC alleles in SLE patients positive for aCL resembles that found in their aCL positive first degree relatives. Since the presence of the antibody is not sufficient to predict a clinical outcome, we studied those patients with reliable clinical data regarding the presence of the antiphospholipid syndrome (aPLS). SLE patients with aPLS had significantly increased frequency of DR7 (pC = 0.004), as did those with probable aPLS (pC = 0.05), while the frequency of DR7 in SLE patients in the doubtful or negative aPLS categories was no different from normal controls. These data support a possible role of DR7 in the development of aCL in SLE patients and their relatives and suggest a contribution of this class II MHC antigen to the development of aPLS within SLE.