HLA-CLASS II RISK ALLELES CONTROL T-LYMPHOCYTE PROLIFERATION IN RESPONSE TO ENTEROVIRUS AND ADENOVIRUS ANTIGENS AND IgG ANTIBODY PREVALENCE IN NEWLY DIAGNOSED T1DM CHILDREN

Abstract

Background: Viral infections are implicated in the pathogenesis of type 1 diabetes mellitus (T1DM) in a number of studies, and playing a role in the initiation of beta-cell damaging process.Objective: To evaluate the T- cell proliferation in response to enterovirus antigens including coxsackievirus B and poliovirus in addition to adenovirus in an HLA- matched population of children with T1DM and children who were healthy, in addition to screening for specific anti-viral IgG antibodies.Subjects and methods: A total of 60 Iraqi T1DM children were included in the presents study. They were newly diagnosed diabetics. For the purpose of comparisons, 50 apparently healthy children were selected. HLA typing was measured by microlymphocytotoxicity, while MTT assay was used for lymphocyte proliferation by culturing peripheral blood lymphocytes (PBLs) with Con-A, Coxsackievirus B5 (CVB5), Adenovirus 3, 4, and 7 serotypes, and Poliovaccine. Serum IgG against these viruses were detected quantitatively with an indirect ELISA.Results & conclusion: 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. Strong T-cell proliferation in response to the tested viral antigens were observed and was 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. High significant mean proliferative percentage for all tested viruses were detected in those patients who were sero-positive IgG as compared to the sero-negative IgG diabetic children.Conclusion: In children with new- onset diabetes, responses were generally decreased, but higher in children who carried risk HLA- class II alleles and who were sero positive to anti- viral IgG antibodies.Key Words: T1DM, HLA class II alleles, Lymphocyte proliferation, Anti- CVB5 IgG, Anti- polio IgG, Anti-adeno IgG.