Immunological Etiology Of Idiopathic Type1Diabetes

Objective:To investigate potential autoimmune characteristics of idiopathic type1diabetes by detection of zinc transporter8autoantibodies (ZnT8A), GAD65-reactive IFN-y secreting T cells (GAD65-IFN-y-T cells), and HLA-DQ susceptible haplotypes.Methods:Fifty-two patients of Hunan Han origin with newly onset idiopathic type1diabetes were enrolled in this study. The criteria for enrolment of idiopathic type1diabetes included:①New-onset, unprovoked ketosis or ketoacidosis at onset;②Negative GADA, IA-2A and IAA;③Prmanent insulinopenia. ZnT8A were detected in all patients with radioligand assay. GAD65-IFN-y-T cells were then determined by enzyme linked immune spot (ELISPOT) in ZnT8A-negative patients. HLA-DQA1and DQB1alleles were identified with 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 for3consecutive years. Comparisons were made between the two groups in their clinical characteristics, ZnT8A and GAD65-IFN-y-T cell status, and isletβ cell function.Results:1) In this study group, ZnT8A was positive in5cases out of52(9.6%).2) GAD65-IFN-y-T cells were positive in2cases out of16patients with negative ZnT8A(12.5%).3) More severe DKA and lower FCP levels at onset (P<0.05) were observed in patients with HLA-DQ susceptible haplotypes.4) There was no significant difference in the positive rate and index of ZnT8A between patients with and without HLA-DQ susceptible haplotypes.5) GAD65-IFN-γ-T cells was positive in1patient carrying HLA-DQ susceptible haplotypes, while there was none in patients with non-susceptible HLA-DQ haplotypes.6) Islet autoantibodies (ZnT8A and IA-2A) turned positive in1patient with HLA-DQ susceptible haplotypes (1/18), while none was observed in patients with non-HLA-DQ susceptible haplotypes during the3-year visiting.7) There was no significant association between FCP and disease duration. Conclusions:1) ZnT8A,GAD65-IFN-γ-T cells exist in some of idiopathic type1diabetes patients.2) Idiopathic type1diabetes patients who carrying HLA-DQ susceptible haplotypes, presented more autoimmune type1diabetes like features, which indicated that the incidence of autoimmune type1diabetes patients is underestimated.