Differential Expression of Nonislet Autoimmunity: Comparison of Korean and U.S. Patients with Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is frequently associated with other autoimmune diseases. The occurrence of common features of autoimmune diseases and the coassociation of multiple autoimmune diseases in the same individual or family support the notion that there may be common genetic factors. We previously reported that immunogenetic markers of T1D were similar in Korean and U.S. families. We hypothesized that nonislet autoimmunity might be expressed in a similar manner in Korean as well as in Caucasian patients and correlated with the DRB1-DQB1 haplotypes. Twenty-five percent of Korean patients with T1D (32/128) had antithyroid autoantibodies (ATA+), whereas eight percent of age-matched controls were ATA+ [OR = 3.7 (95% CI:1.0-12.0), P < 0.05]. Twenty-three percent (84/369) of age-matched T1D patients from the U.S. had ATA (not statistically different from that in Koreans). None of the Korean patients nor the family members were positive for 21-hydroxylase (21OH) or transglutaminase autoantibodies (TG). In contrast, in U.S. patients, nine T1D patients (2.4%) were 21OH+ (not statistically different from that in Koreans) and 39 T1D patients (10.6%) were TG+ [OR = 30.7 (95% CI: 4.6-111), P < 10(-4) vs. Korean patients]. Nonislet autoimmunity is prevalent in Korean and U.S. patients with T1D and their family members, but specific forms of autoimmunity differ even after matching for their HLA haplotypes. Individuals with T1D and their relatives frequently develop a panel of autoantibodies, perhaps due to other common susceptibility genes that are shared among first-degree relatives.

Glutamic Acid Decarboxylase 65 and Islet Cell Antigen 512/IA-2 Autoantibodies in Relation to Human Leukocyte Antigen Class II DR and DQ Alleles and Haplotypes in Type 1 Diabetes Mellitus

“…Multinomial regression analysis revealed a positive association of the haplotype DRB1*040101/DQB1*0302 with altered anti-IA-2 titers in our population. These results are concordant with previous studies on Canadian (24), Japanese (20), German (10), Finnish (27,28), Italian (13), and Belgian (5) populations that showed that the prevalence and level of IA-2 autoantibody are increased in patients with HLA DR4/DQ8. However, IA-2 was negatively associated with DRB1*110101/ DQB1*030101 in titers and in prevalence.…”

“…GAD and IA-2 are two of the major and bestcharacterized autoantigens. Several studies have demonstrated that HLA-DQ and -DR alleles influence T1D susceptibility (1,20,21,29), and T1D-predisposing or -protective HLA-DQ and -DR alleles were identified (1,29). Apart from the regulation of the autoreactive T cell repertoire by susceptible and protective HLA molecules, presentation of autoantigenic peptides by specific HLA molecules or induction of regulatory T cells (Treg) explains, at least in part, the modulatory capacity of HLA variants on the overall T1D risk (8).…”

Evidence for the role of STAT4 as a general autoimmunity locus in the Korean population

“…Although the exact nature of autoimmunity of thyroid has not been fully elucidated, there is a wealth of evidence that AITDs develop in genetically susceptible individuals, in conjunction with environmental triggers [4]. λs, an indicator of familial aggregation, has been reported to be between 5.9 and more than 10 in AITDs, suggesting a strong genetic component in the development of the disease [5].…”