DISTRIBUTION OF HLA CLASS I AND CLASS II ANTIGENS IN T1DM CHILDREN AND THEIR SIBLINGS

Abstract

Background: Genomic studies have confirmed that the main locus defining the genetic susceptibility to T1DM is encoded within the Major Histocompatibility Complex- HLA (Human Leukocyte Antigen) region on human chromosome 6.Objective: To investigate the role of HLA-class I and class II antigens in the etiology of type 1 diabetes mellitus (T1DM) and in prediction of this disease in siblings.Patients & methods: Sixty T1DM children who were newly onset of the disease (diagnosed less than five months) were selected. Their age ranged from 3-17 years. Another 50 healthy siblings were available for investigation of HLA-typing, their ages range from 3-16 years. Eighty apparently healthy control subjects, matched for age (4-17) years, sex and ethnic backgrounds (Iraqi Arabs), underwent the HLA-typing. Serological typing of HLA antigens was done by microlymphocytotoxicity assay.Results & recommendations: At HLA-class I region, T1DM patients showed a significant increased frequency of antigens A9 (40.0 vs. 18.75%) and B8 (28.33 vs. 8.75%) as compared to control subjects, while 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 associated with 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. It is potentially valuable to predict TIDM in siblings by screening for HLA risky alleles in correlation with autoantibodies