Tu127 - HLA Class II Association of Autoantibodies Against GAD65 in North Indian Type 1 Diabetes Patients

Neeraj Kumar – Scientist D, Infection Biology, ICMR-National Institute of Pathology, New Delhi; Neetu Mishra – Associate Professor, Medical and Health Sciences, Symbiosis International (Deemed University), Pune; Nikhil Tandon – Head of Department, Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi; Gunja Mishra – Infection Biology – ICMR-National Institute of Pathology, New Delhi; Narinder Mehra – Emeritus Scientist, Indian Council of Medical Research, New Delhi

Abstract Text: AIM AND

Objective: This study was planned to evaluate the genetic association of HLA class II genes/haplotypes with the presence of autoantibodies against GAD65 (GADA) in study subjects from North India.

Methods: GADA in the sera of 252 T1D patients and 230 healthy controls were quantified using ElisaRSR™GADAb kit (RSR Ltd., UK). Genomic DNA was extracted using a modified ammonium acetate salting-out method. HLA genotyping was performed using HystoType SSP DR/DQ Combi Pack kit (BAG Healthcare, Germany).

Results: Out of 252 T1D patients screened for the presence of GADA, 128 (50.79%) patients were GADA+, while only 2 out of 230 healthy subjects were GADA+ (0.87%; p=2.09e-34). Prevalence of GADA was found to be comparable in recently-diagnosed (RD) versus long-standing (LS) patients (58.18% vs 48.73%) as well as in patients with age at disease onset (ADO) < 18 years versus ≥18 years (55.41% vs 44.23%). GADA positivity was also comparable in DR3+RD versus DR3+LS patients (50.91% vs 440.61%) as well as in DR3+ patients with ADO < 18 years versus ≥18 years (47.30% vs 38.46%). HLA-DRB1*03 and -DQB1*02 frequencies were significantly increased in GADA+ versus GADA‒ patients {91.41% vs 66.13; Pc=1.11e-5; OR=5.45(95%CI=2.67-11.08) and 94.53% vs 73.39%; Pc=2.19e-5; OR=6:27(95%CI=2.70-14.49), respectively}. Further, our data revealed a significantly increased frequency of DRB1*03-DQB1*02 haplotype in GADA+ versus GADA‒ patients {60.55% vs 41.94%, P=3.94e-5; OR=21.3(95%CI=1.49-3.03)}.

Conclusion: Our study points to a central role of DRB1*03 and DQB1*02 genes in initiating and driving GAD65-mediated autoimmune response that possibly led to progressive loss of β-cells and development of T1D.