Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population.

BACKGROUND

It has been reported that HLA class II haplotypes DRB10405-DQA10303-DQB10401 and DRB10901-DQA10302-DQB10303 are major susceptibility haplotypes for type 1 diabetes mellitus (DM) in Japanese population. However, little has been reported on the susceptibility HLA class II haplotypes in Japanese patients with autoimmune polyglandular syndrome type II and type III (APS III).

PATIENTS AND METHODS

HLA class II haplotypes of DRB1-DQA1-DQB1 in 31 patients with APS III, 14 patients with Hashimoto's thyroiditis alone, and 15 patients with Graves' disease alone were examined in Japanese population. APS III patients were divided into three groups (A, B, and C) depending on the combination of autoimmune endocrine diseases.

RESULTS

In 13 APS III patients with both Hashimoto's thyroiditis and type 1 DM (group A), the haplotype frequencies of the HLA DRB10802-DQA10401-DQB10402 and DRB10901-DQA10302-DQB10303 were significantly higher than in the controls. In patients with Hashimoto's thyroiditis alone, the haplotype frequency of DRB10901-DQA10302-DQB10303 was significantly higher than in controls, whereas the frequency of DRB10802-DQA10401-DQB10402 did not differ significantly from those in the controls. In 11 APS III patients with both Graves' disease and type 1 DM (group B), the haplotype frequencies of HLA DRB10405-DQA10303-DQB10401 and DRB10802-DQA10301-DQB10302 were significantly higher than in controls. In patients with Graves' disease alone, the haplotype frequency of DRB10803-DQA10103-DQB10601 were significantly higher than those in controls, suggesting that the susceptibility haplotypes for group B APS III differed from those for Graves' disease alone. In 7 APS III patients with both autoimmune thyroid diseases and pituitary disorders (group C), the haplotype frequency of HLA DRB10405-DQA10303-DQB10401 was significantly higher than in controls.

CONCLUSIONS

Susceptible HLA class II haplotypes of DRB1-DQA1-DQB1 for APS III differ between the Japanese and Caucasian populations. More interestingly, the susceptible HLA class II haplotypes differ among the three types of Japanese APS III and are not merely a combination of susceptibility haplotypes of each endocrine disease.