Relation of Coxsackie B3 and B4 Viral Infections for Development of type 1 Diabetes Mellitus in Children: A Case-Control Study

Abstract

Background: Human Type 1 diabetes (T1D), previously called Juvenileonset diabetes is one of the most common chronic, multifactorial diseases of autoimmune origin with a strong genetic component, affecting about 542 000 children in the world and represents about 5-10% of all cases of diabetes. Human enteroviruses (HEVs), particularly Coxsackie B viruses (CVBs), might trigger the onset of type 1 diabetes (T1D). Objectives: Find out any relation between the Coxsackie virus type B3 & B4 infections in addition to GAD65 autoantibodies and the development of T1DM Patients and Methods: A matched case-control study was conducted and sixty cases and 120 controls were enrolled in the study.Enzyme-Linked Immunoassay (ELIZA) technique was used to detect IgM and IgG in serum against the Coxsackie B3 , B4 and GAD65 (Glutamic Acid Decarboxylase 65) autoantibodies of both cases and controls. Qualitative detection of the RNA of the Coxsackie B3 & B4 viruses in the cases and controls by the conventional PCR method using suitable primers in both cases and control. Molecular detection of the CB3 and CB4 RNA was done using according to the manufacturers' instruction. Results:The following risk factors were found to be independently associated with illness, it were significantly associated with illness and at higher risk of T1DM : CB4 IgM Positivity (OR 47 [95% = 6.1-364.1], p = 0.0002).), CB4 RNA Positive (OR 39.6 [95%CI= 5.1-309], p = 0.0004 IgG Antibodies against both CVB3 and GAD65 (OR 32.9 [95%CI = 4.2-258.7], p = 0.0009). , GAD65 IgG Positivity (OR 11.8 [95% CI = 4.4-31.2], p = 0.001).and IgM Antibodies against both CB4 andGAD65 (OR 8.8 [95%CI = 2.7-28.2], p = 0.0002). other risk factors like CB3 IgM Positivity (OR 1.7 [95%CI = 0.6-4.5] p= 0.2),CB3 IgG Positivity((OR 1.3 [95%CI = 0.7-2.4], p=0.3).CB4 IgG Positivity(OR 2.1 [95%CI = 0.9-44], p = 0.06) and IgM-Antibodies against both CB3andGAD65 ((OR 1.3 [95%CI = 0.3-5.0], p = 0.6) with a moderately increased risk of illness, but these were not statistically significant. CB3 RNA Positive (OR 0.8 [95%CI= 0.3-1.9] p = 0.6), GAD65 IgM Positivity (OR 0.7 [95%CI = 0.4-1.5], p = 0.7), IgG Antibodies against both CB4-GAD65 (OR 0.9 [95%CI = 2.9-8.8], p = 0.05) was not associated with illness as these were not statistically significant with the decreased risk of illness and has protective role against infection with T1D. Conclusions: We propose that children aged less than 17 years are at risk of T1D infection if exposure to CB4 whereas CB3 has protective role.