HLA haplotypes in a family with multiple cases of rheumatoid arthritis.

Population studies have identified the histocompatibility antigen HLA-DR4 to be a genetic marker of significantly increased risk for the development of rheumatoid arthritis (RA). Family studies are now beginning to elucidate the role of this and other genetic factors in the pathogenesis of RA. We have studied a large family in which the mother and 3 of the 6 children have seropositive RA. One maternal and 1 paternal HLA haplotype contain HLA-DR4. The mother and the 2 children with the maternal DR4 containing haplotype have RA. One sibling inherited neither of the DR4 haplotypes, yet developed RA at age 20. The inheritance of RA in this family illustrates the complexity of the genetic predisposition to this immunologically mediated disorder.