ROLE OF HLA GENES IN HUMAN DISEASE

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We have defined an HLA locus (DP) which maps centromeric to the other known genes of the HLA complex. We are analyzing the importance of the genetic region marked by this gene in human disease. Family and population studies have been performed to analyze genetic control of pauciarticular juvenile rheumatoid arthritis. The data indicate that: 1) DPw2 is a new marker for susceptibility to pauciarticular JRA; 2) an individual's susceptibility to disease is influenced by at least two HLA-linked genes: one that is associated with DPw2 and another (or othrs) that is associated with DR5 or DRw8; 3) these susceptibility genes confer risk for the disease whether present on the same haplotype or opposite haplotypes. Studies are continuing on the frequency and importance of DP-mismatch on bone marrow transplantation between otherwise HLA-identical siblings. One DP-DR recombination has been identified in studies of 18 donor-recipient pairs. This finding increases confidence in the estimates of recombination frequency between DR and DP; together with further studies, this data will allow interpretation of the role of DP-mismatch in bone marrow transplantation.