HLA-DR genotypes in familial rheumatoid arthritis: increased frequency of protective and neutral alleles in a multicase family.

Abstract

We describe a unique family where each of the 5 siblings in the second generation has rheumatoid arthritis (RA). Two other members of the family have RA and systemic lupus erythematosus (SLE), respectively. No members of previous generations in the family had documented inflammatory arthritis. Due to the suspected genetic predisposition, HLA-DR genotypes were determined in the affected siblings and their parents, children, and grandchildren. We investigated the possible role of various HLA-DR alleles in the evolution of RA in this multicase family. HLA-DRB1* alleles were determined by polymerase chain reaction using the sequence-specific primer-Olerup method. The most common alleles in the 6 persons with RA were HLA-DRB1*07 and DRB1*15, which are known to be protective and neutral in RA. No patient or family member carried any HLA-DR4 alleles. HLA-DRB1*07 and DRB1*15 alleles are thought to be protective or neutral in RA. However, the majority of RA patients in the family and nearly half of all family members carried these alleles, suggesting a role of these genotypes in susceptibility to RA. No RA patient in this family carried HLA-DR4 alleles. Thus, in our rare family with 6 RA cases, an unexpected genetic background may be involved in the increased susceptibility to inflammatory arthritis.