Relationship among 64k Autoantibodies, Pancreatic β-cell Function, HLA-DR Antigens and HLA DQ Genes in Patients with Insulin-Dependent Diabetes Mellitus in Korea

Abstract

ObjectivesAmong autoantibodies detected in patients with insulin-dependent diabetes mellitus(IDDM), antibodies to 64,000Mr islet protein(64k), now recognized as glutamic acid decarboxy lase(GAD), appear to be an even more predictive marker of IDDM than islet cytoplasmic antibody(ICA) or insulin autoantibody(IAA). We examined the relationships among 64k autoantibodies, pancreatic β-cell function, HLA-DR antigens and HLA-DQ genes in patients with IDDM in Korea.MethodsTo identify the 64k autoantibody, the immunoprecipitation method was performed for 35 patients with IDDM and 10 normal controls. In patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and HLA-DQA1 and DQB1 gene typings were performed.Results12 of 35(34%) patients with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal controls. There were no differences in residual pancreatic β-cell function between 64k autoantibody positive and negative groups. 64k autoantibody was detected more frequently in patients with recent(duration< 6 months, 10/25[40%]) and young -aged(age< 15 years, 7/18[39%]) onset of IDDM. All of 3(100%) patients with HLA-DR3/DR4 heterotypes were positive in 64k autoantibody, in contrast to 1 of 7(14%) patients without HLA-DR3 nor DR4. The frequencies of HLA-DQA1*0301, HLA-DQB1*0201, DQB1*0302 and DQB1*0303 gene types were higher in patients with 64k autoantibody (12/12[100%]) vs. without 64k autoantibody 18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs. without 64k autoantibody 8/22[36%] and 6/11[55%] vs. without 64k autoantibody 9/22[41%].ConclusionsThere results suggest that 64k autoantibodies have some relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic β-cell function in Korean patients with IDDM.

Clinical Characteristics, and Time Course of Pancreatic β-Cell Function and Glutamic Acid Decarboxylase Antibodies in Thai Patients with Adult-Onset Type 1 Diabetes: Distinction Between Patients of Rapid- and Slow-Onset

“…Our study showed that, despite comparable duration of diabetes, fasting C-peptide levels of rapid-onset Type 1 diabetic patients was significantly lower than those of slow-onset, which indicates the greater residual 13 cell mass of the latter. Clinical characteristics of adult patients with rapid-onset Type 1 diabetes in this study, except those of an older age at onset, are similar to those of childhood Type 1 diabetes reported elsewhere [4,9,10,21,22]. They had remarkably low fasting C-pep-378 tide levels, lean BMI and positive history of ketonuria or ketoacidosis.…”

“…Asian population is sparse [20][21][22]. Most studies were done in a mixed population of patients with childhood-and adultonset.…”

Anti‐GAD65 autoantibody in Taiwanese patients with insulin‐dependent diabetes mellitus: effect of HLA on anti‐GAD65 positivity and clinical characteristics

“…On the other hand, different structures of MHC molecules might affect antigen processing and presentation of GAD. There are only a few reports which address the question of how HLA antigens relate to GAD autoimmunity Lee et al, 1995]. Identification of a peptide sequence in GAD for T cell reactivity in human IDDM [Lohmann et al, 1994;Panina-Bordignon et al, 1995] and for prevention of IDDM in NOD mice [Tisch et al, 1993;Elliott et al, 1994;Gelber et al, 1994;Pleau et al, 1995] further substantiates the involvement of HLA molecules in GAD autoimmunity and the pathogenesis of IDDM.…”

GAD65 antibody prevalence and association with c-peptide, HLA class II alleles in Beninese patients with type 1 diabetes

“…[8][9][10] There were only few studies concerning how HLA alleles relate to GAD autoimmunity. 11,12 In addition, some Asian population have shown rather low frequencies (5-50%) of GAD65 and ICA in T1D when compared with Caucasian recent onset T1D patients (63-84%). [13][14][15][16][17][18] GAD65Ab can be measured by radioimmunoassay.…”