Human Leukocyte Antigens class II influence the expression of Glutamic Acid Decarboxylase auto antibodies in Type Diabetic children and their Siblings


Background: The immunogenetic predisposition may be considered as an important factor for the development of Type 1 Diabetes Mellitus (T1DM) in association with the HLA antigens. Objective:This study was designed to investigate the role of HLA-class II antigens in the etiology of type T1DM and in prediction of this disease in siblings, and its effect on expression of glutamic acid decarboxylase autoantibodies (GADA). methods:Sixty children who were newly diagnosed type 1 diabetes (diagnosed less than five months) were selected. Their age ranged from 3-17 years. Another 50 healthy siblings were available for this study, their ages range from 3-16 years. Eighty apparently healthy control subjects, matched with age (4-17) years, sex and ethnic backgrounds (Iraqi Arabs) underwent the HLA-typing examination. Finally 50 healthy individuals were selected randomly to undergo GADA test.Results:At HLA-class II region, DR3 and DR4 were significantly increased in patients (53.33 vs.26.25% and 50.0 vs. 12.5% respectively) as compared to controls. In addition to that, T1DM was significantly associatedwith DQ2 (33.33 vs.15%) and DQ3 (40.0 vs.20%) antigens as compared to controls, suggesting that these antigens had a role in disease susceptibility, while the frequency of DR2 and DQ1 antigens were significantly lowered in patients compared to controls (6.66 vs.25% and 6.66 vs.22.5% respectively). These molecules might have protective effect. In siblings a significant increase frequency of DR4 antigen (34.0 vs.12.5%) was observed in comparison to controls, suggesting that it might be much useful for predicting T1DM in affected families.Anti-GAD autoantibodies were present in 50% of Type 1Diabetic children, and in 16% of their siblings. High proportion of GADA was found in the patients carrying HLA-DR3/DR4 heterozygous.conclusion:Both the T1DM patients and their siblings shared the HLA- DQ1 as protective antigens, while DR3 and DR4 were susceptible one, and high proportion of GADA was found in the T1DM patients and siblings carrying HLA-DR3/DR4 heterozygous.