Role of human leukocyte antigen DQ haplotypes for immunoetiologic classification of idiopathic type 1 diabetes

Abstract

Objective To investigate the role of human leukocyte antigen (HLA) DQ haplotype for immunoetiologic chassification of idiopathic type 1 diabetes by comparison of clinical features, zinc transporter 8 autoantibodies (ZnT8A), glutamic acid decarboxylase 65(GAD65)-reactive interferon-γ-secreting T cells (GAD65-IFN-γ-T cells). Methods Fifty-two patients of Han People of Hunan Province origin with newly onset idiopathic type 1 diabetes were enrolled in this study from March 2000 to December 2011. The criteria for enrolment included: new-onset, unprovoked ketosis or ketoacidosis at onset; negative glutamic acid decarboxylase antibody(GADA), protein tyrosinephosphatase antibody (IA-2A) and insulin autoantibody(IAA); permanent insulin deficiency. ZnT8A were detected in all patients with radioligand assay. GAD65-IFN-γ-T cells were tested by enzyme linked immune spot (ELISPOT) in ZnT8A-negative patients. HLA-DQA1 and DQB1 alleles were identified with polymerase chain reaction(PCR) sequence-based genotyping (SBT). According to the situation of HLA-DQ susceptible haplotypes, patients with HLA-DQ genotyping were categorized into two groups, and were all visited annually for 3 consecutive years. Comparisons were made between the two groups in their clinical characteristics, ZnT8A and GAD65-IFN-γ-T cell status. Compare of qualitative data between two groups was progressed by using chi-square test. Results In this study group, ZnT8A was positive in 5 cases out of 52 (9.6%), and GAD65-IFN-γ-T cells were positive in 2 cases out of 16 patients with ZnT8A negative (12.5%). More severe diabetic ketoacidosis(DKA)(Z=-2.84, P<0.05) and lower fasting C protein(FCP) levels(χ2=0.38, P<0.05) at onset were observed in patients with HLA-DQ susceptible haplotypes. During the onset, GAD65-IFN-γ-T cells was positive in 1 patient carrying HLA-DQ susceptible haplotypes and there was none in patients with non-susceptible HLA-DQ haplotypes. Islet autoantibodies (ZnT8A and IA-2A) turned positive in 1 patient with HLA-DQ susceptible haplotypes(1/18), while none was observed in patients with non-HLA-DQ susceptible haplotypes during the 3-year visit. Conclusions ZnT8A and GAD65-IFN-γ-T cells exist in some patients with idiopathic type 1 diabetes.The patients with idiopathic type 1 diabetes carry HLA-DQ susceptible haplotypes, compared with those without HLA-DQ haplotypes, present a autoimmune tendency.It implies that islet autoimmunity, to some extent, could be an etiology of idiopathic type 1 diabetes, which is probably mediated by HLA-DQ hapalotype. Key words: Diabetes mellitus, type 1; Human leukocyte antigen; Classification; Immunology