Immunogenetics of Hashimoto's and Graves' diseases

Haplotypes of the human major histocompatibility complex (HLA) and the immunoglobulin allotype (Gm) were analyzed in all 243 members of 37 families in which 2 or more first degree relatives had Graves' disease. In 10 families with 70 members where 1 or more first degree relatives had Hashimoto's disease, 26 (37%) had Graves' disease, and 14 (20%) had Hashimoto's disease. In the other 27 families, consisting of 173 members, 70 (40%) had Graves' disease, and none had Hashimoto's disease. The disease-associated haplotypes of HLA and Gm for each family were identified by determining the haplotypes concordant in 2 members with Graves' disease. In 10 families with Graves' and Hashimoto's diseases, all 14 members with Hashimoto's disease had the same disease-associated haplotypes of both HLA and Gm as had members with Graves' disease in each family. Among 96 members with Graves' disease in 37 families, 74 were used for the determination of the disease-associated haplotypes. In the remaining 22 members with Graves' disease, 21 had both disease-associated haplotypes in their families. Our findings in these families suggest that 1) in Hashimoto's disease as in Graves' disease, two genes linked to HLA and Gm, respectively, control the susceptibility of the disease; 2) common immunogenetic factors are involved in the pathogenesis of both Hashimoto's and Graves' disease, and 3) those who do not have immunogenetic factors are very unlikely to develop Hashimoto's or Graves' disease.