The Biologic Significance of The HLA-Bw52-DHO Haplotype

Abstract

HLA-Bw52-DHO haplotype, formed due to a strong linkage disequilibrium between Bw52 and DHO, is characteristically seen in the Japanese population. The biologic significance of this haplotype in the genetic control of the immune response and in the control of disease susceptibility was investigated. The immune response to tetanus toxoid showed a clear bimodal distribution among the healthy Japanese population, indicating that there exist high and low responders to this antigen. Since low responders to tetanus toxoid had a significant association with HLA-Bw52-DHO haplotype and were all heterozygous at the HLA-D locus, the low responsiveness to tetanus toxoid is perhaps controlled by an immune suppression gene which is in linkage disequilibrium with HLA-Bw52-DHO. Graves' disease, known to be one of the organ specific autoimmune diseases, was shown to be associated with HLA-Bw52-DHO in the Japanese population. In Caucasians, however, Graves' disease has been reported to be associated with HLA-B8-Dw3, a haplotype completely absent from the Japanese population. These data suggest that the HLA-Bw52-DHO haplotype is a counterpart of the Caucasian HLA-B8-Dw3 haplotype with respect to its biologic significance. As the susceptibility to the organ specific autoimmune diseases has been shown to be controlled by immune response genes in mice, it is suggested that one of the most important genetic factors controlling the susceptibility to Graves' disease is an immune response gene shared by the HLA-B8-Dw3 and HLA-Bw52-DHO haplotypes.