HLA-DR4 and Gm 1;21 haplotypes are associated with pseudolupus induced by venopyronum dragées.

Abstract

The phenotypic frequencies of human major histocompatibility complex class I, II, and III antigens and immunoglobulin allotypes (Gm factors) were determined in 56 patients (55 women, 1 man) who had lupus-like disease induced by venopyronum dragées. The findings in these patients were compared with those of a control group. We found a significant increase of HLA-DR4 (57.1% versus 26.5%, relative risk [RR] 3.7) and a decrease of HLA-DR3 (3.6% versus 19.1%, RR 0.16) in the patient group. In addition, the haplotype Gm 1;21 (60.7% versus 32.9%, RR 3.2), and the phenotype Gm 1,3;5,21 (46.4% versus 25.8%, RR 2.5) were significantly increased. Both the haplotype Gm 1;21 and the phenotype Gm 1,3;5,21 are associated with HLA-DR4 in pseudolupus patients but not in controls. The coincidence of HLA-DR4 and Gm 1;21 markedly increases the risk of acquiring pseudolupus (RR 6.9). We conclude that the pathogenesis of pseudolupus is influenced by at least 2 independent genetic factors. A similar HLA association has been described in hydralazine-induced lupus, and this suggests a common pathogenic mechanism.