Immunogenetics of early-onset insulin-dependent diabetes mellitus among the Japanese: HLA, Gm, BF, GLO, and organ-specific autoantibodies — the J.D.S. study

The Japan Diabetes Society (JDS) conducted a multicenter study on the immunogenetics of early-onset insulin-dependent diabetes mellitus (IDDM) of the Japanese. Human leukocyte antigen (HLA), properdin factor B (BF), immunoglobulin heavy-chain complex (Gm), and glyoxalase of erythrocytes (GLO) were typed, and organ-specific autoantibodies, including islet cell antibody (ICA), were assayed in 159 Japanese IDDM patients and their family members and in 258 healthy Japanese controls. The HLA-DRw9 phenotype and HLA-Bw61/DRw9 haplotype were significantly increased among the patients with autoantibodies other than ICA but with no autoimmune diseases (RR = 5.84, cP less than 0.001; and RR = 7.45, P less than 0.001), whereas the HLA-DR4 phenotype and HLA-Bw54/DR4 haplotype were significantly increased in those without either the autoantibodies or autoimmune diseases (RR = 2.64, cP less than 0.001; and RR = 4.55, P less than 0.001). The HLA-DR4 phenotype was significantly increased in the patients with autoimmune thyroid diseases (RR = 6.21, cP less than 0.05). In all groups of patients, the HLA-DR2 phenotype was significantly decreased, and the relative risk of the HLA-DRw9/DR4 genotype was highest among all HLA-DR genotypes. No significant association was found between HLA type and the duration or incidence of ICA. Gm types of g and gft were significantly increased in the patients with the autoantibodies (RR = 2.11, P less than 0.05; and RR = 34.11, P less than 0.05), whereas the BF-F phenotype was significantly decreased in the patients either with or without autoantibodies (RR = 0.43, P less than 0.05; and RR = 0.46, P less than 0.05). There was no association between IDDM and GLO type. These data indicate that immunogenetic bases underlying IDDM of the Japanese are heterogeneous, as are those in Caucasians.