Association between HLA-class ii alleles and T-cell proliferation in response to enterovirus and adenovirus antigens in newly diagnosed children with type 1 diabetes mellitus

Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus [T1DM], either through direct beta-cell infection or as triggers of autoimmunity. To evaluate the T- cell proliferation in response to Enterovirus antigens including Coxsackicvirus B and Poliovirus in addition to Adenovirus in an HLA- matched population of children with T1DM and children who were healthy. A total of 60 Iraqi T1DM children were included in the presents study. They were new onset of the disease. For the purpose of comparisons, 50 apparently healthy control subjects were 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 Poliovaccin. No significant differences were shown in the PBL proliferative percentage in response to Con-A mitogen and tested viruses [CVBs 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

Genetic characteristics and beta-cell autoimmunity in T1DM children

T1DM is known to be polygenic disease that appears from the interaction of mutation in multiple genes including HLA. The autoimmune mediated destruction of pancreatic beta-cells is reflected by the presence of autoantibodies against prominent antigens in the pancreatic beta-cells. This study was designed to investigate the role of HLA-class I and class II antigens in the etiology of type 1 diabetes mellitus [T1DM] and also assessment of glutamic acid decarboxylase [GAD[65]] autoantibodies in the patients at the onset of the disease. Sixty T1DM patients who were newly onset of the disease [diagnosed less than five months] were selected. Eighty apparently healthy control subjects, matched with age, sex and ethnic backgrounds underwent the HLA-typing by lymphocytotoxicity assay. Finally 50 healthy individuals were selected randomly to undergo serological assessment of GAD[65] autoantibodies using IRMA method. At HLA-class I region, T1DM patients showed a significant increased frequency of antigen A9 [40.0 vs. 18.75%] and B8 [28.33 vs.8.75%] as compared to control subject. 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 haplotypes 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 had protective effect. Anti-GAD[65] autoantibodies were present in 50% of T1DM children especially in older ages and in females more than males. High proportion of GADA was found in the patients carrying HLA-DR3/DR4 heterozygous. In conclusion, susceptibility to T1DM is genetically controlled

Investigation of circulating anti-coxsackie B, anti- polio and anti-adeno IgG in newly diagnosed T1DM children

Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus [T1DM], either through direct beta-cell infection or as triggers of autoimmunity. To investigate the presence of specific anti- viral IgG antibodies for Coxsackie virus type B [CVB5], Poliovirus, and Adenovirus which proposed to be involved in the etiology of T1DM. A total of 60 Iraqi T1DM children were included in the present study. They were new onset of the disease [diagnosis was from one week up to five months]. For the purpose of comparisons, 50 apparently healthy control subjects were selected. Serum IgG against Coxsackie virus type B[5], Adenovirus type 3, 4, and 7, and Poliovaccin Trivalent were detected quantitatively with an indirect ELISA. High proportion of anti-CVB5 IgG [20%][p<0.05] and anti- Polio IgG [31.67%] were found in T1DM children compared to controls [8%, 26% respectively], while anti- Adeno IgG were detected in diabetic patients only [6.67%][p<1.0001]