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

Abstract

Anti-GAD65 antibody has been studied widely in patients with insulin-dependent diabetes mellitus (IDDM) in many different populations. However, the prevalence of GAD65 autoantibody has not been assessed in Taiwanese patients with IDDM. We therefore characterized GAD65 antibody and investigated the effect of HLA-DR phenotypes on GAD65 autoimmunity and other clinical characteristics in Taiwanese subjects with IDDM. Two hundred and twenty-five patients (male 102, female 123) with IDDM were recruited. The diagnostic criteria for IDDM were age of onset before 30 years, presence of diabetic ketoacidosis, and insulin-dependency within 3 years of onset. We employed a radioligand method to detect GAD65 antibody. HLA-DR typing was performed by the PCR-SSO techniques. Plasma C-peptide and anti-thyroid microsomal antibody were also measured. The prevalence of GAD65 antibody according to duration of disease were 50/91 (54.9%), 37/95 (38.9%), 8/24 (33%), and 3/15 (20%) among the groups of duration < or = 5, 6-10, 11-15, and > 15 years, respectively (p = 0.0011). There were no significant differences between GAD(+) and GAD(-) patients in age of onset (11.5 +/- 6.5 and 11.6 +/- 13.4 years, respectively), gender distribution (male:female 39:59 and 58:69, respectively) and percentage with residual beta cell function (38.8% and 29.1%, respectively). Multiple regression analysis revealed that duration of IDDM correlated inversely with residual beta cell function. Earlier onset of IDDM correlated with a loss of beta cell function and a HLA-DR phenotype containing DR3/4, DR3/3 or DR3/9. Prevalence of GAD65 autoantibody among Taiwanese subjects with IDDM was negatively correlated with duration of disease. Different determinants in the HLA-DR locus contributed to the clinical onset of IDDM but not to GAD autoimmunity.