Susceptibility Alleles and Haplotypes of Human Leukocyte Antigen DRB1, DQA1, and DQB1 in Autoimmune Polyglandular Syndrome Type III in Japanese Population

Abstract

Background: It has been reported that HLA class II haplotypes DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0901-DQA1*0302-DQB1*0303 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 DRB1*0802-DQA1*0401-DQB1*0402 and DRB1*0901-DQA1*0302-DQB1*0303 were significantly higher than in the controls. In patients with Hashimoto’s thyroiditis alone, the haplotype frequency of DRB1*0901-DQA1*0302-DQB1*0303 was significantly higher than in controls, whereas the frequency of DRB1*0802-DQA1*0401-DQB1*0402 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 DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0802-DQA1*0301-DQB1*0302 were significantly higher than in controls. In patients with Graves’ disease alone, the haplotype frequency of DRB1*0803-DQA1*0103-DQB1*0601 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 DRB1*0405-DQA1*0303-DQB1*0401 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.

Type 1 Diabetes Mellitus Associated with Graves' Disease and Vogt-Koyanagi-Harada Syndrome

“…VKH syndrome is strongly associated with HLA-DRB1 * 0405 and DQB1 * 0401 genes (7) which are also susceptible genes of type 1 diabetes and Graves' disease in Japanese population (8,9). In the present case, the patient had both HLA-DRB1 * 0405 and DQB1 * 0401 genes.…”

“…However, there are only three reports on association between type 1 diabetes and VKH syndrome (10)(11)(12), and only one report on association between Graves's disease and VKH syndrome (13). Conversely, type 1 diabetes is often associated with Graves' disease (9) (1,16). Progression of β-cell destruction in SPIDDM is slow (16), and SPIDDM is associated with HLA-DR4-DQA1 * 0301-DQB1 * 0401 haplotype (17) which is identified in a large proportion of patients with VKH syndrome (7).…”

Simultaneous Occurrence of Type 1 Diabetes Mellitus and Graves' Disease: A Report of Two Cases and a Review of the Literature

“…GD) and T1D alone. The frequencies of DRB1* 09:01 and DQB1*03:03 in the previously reported APS3v cases in which T1D and GD had either developed or been diagnosed simultaneously were higher than the frequencies in the 11 Japanese APS3v (T1D and GD) patients reported by Hashimoto et al (15), but the difference in DRB1*09:01 was not statistically significant ( Table 3). The risk of the simultaneous occurrence of T1D and GD might be higher in APS3v patients with HLA DRB1*09:01-DQB1*03:03 than in those with DRB1*04:05-DQB1*04:01.…”

“…The alleles and haplotypes associated with acute-onset and those associated with slowly progressive T1D are similar (14). Hashimoto et al (15) reported that the characteristics of susceptibility HLA haplotypes differed among patients with APS3v (T1D and GD), T1D alone and GD alone. GD) and T1D alone.…”

Onset of type 1 diabetes mellitus and heparin‐induced thrombocytopenia in a patient with Basedow's disease and idiopathic thrombocytopenic purpura: Novel combination as autoimmune polyglandular syndrome

“…As she had various autoimmune disorders, such as Basedow's disease, ITP and type 1 diabetes mellitus, we diagnosed her with APS type 3. Human leukocyte antigen typing was as follows: DRB1, *04:05, *08:03; DQB1 04:01, 06:01, which were also compatible with type 1 diabetes mellitus and APS type 33. Hyperglycemia and ketoacidosis gradually recovered with fluid replacement and insulin therapy.…”