ASSOCIATION BETWEEN HLA-CLASS II ALLELES AND T-CELL PROLIFERATION IN RESPONSE TO ENTEROVIRUSES AND ADENOVIRUS ANTIGENS IN NEWLY DIAGNOSED CHILDREN WITH TYPE 1 DIABETES MELLITUS

Abstract

Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus (T1DM), either through direct β-cell infection or as triggers of autoimmunity. T- cell proliferation was evaluated in response to Enteroviruses antigens including Coxsackievirus B and Poliovirus in addition to Adenovirus in an HLA- matched population of children with T1DM and in children who were apparently healthy. A total of 60 Iraqi T1DM children were included in the presents study. They were with new onset of the disease. For the purpose of comparisons, 50 apparently healthy control subjects were also selected. HLA typing was measured by microlymphocytotoxicity, while methylthiazoltetrazolium (MTT) assay was used for lymphocyte proliferation by culturing peripheral blood lymphocytes (PBL) with Coxsackievirus B5, Adenovirus 3, 4 and 7 and Poliovaccine. No significant differences were shown in the PBL proliferative percentage in response to Con-A mitogen and tested viruses (CVB5 and Adenovirus) between T1DM and healthy controls, but PBL proliferative percentage of patients showed a significant decline in response to Poliovaccine. HLA class II (-DR3, DR4, DQ2 and DQ3) antigens were significantly increased in T1DM patients and they played an important role in the etiology of the disease. Strong T-cell proliferation in response to the tested viral antigens were observed to be related to HLA-DR4 and HLA-DQ3 antigens, whereas the HLA-DR3 and HLA-DQ2 alleles were associated with week responsiveness to the same antigens. However, in children with new- onset diabetes, responses were decreased and this could be caused by trapping of virus- specific T- cells in the pancreas.