Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children

Abstract

Aims/hypothesis. We evaluated the role of enterovirus infections in the pathogenesis of Type I (insulindependent) diabetes mellitus by monitoring enterovirus antibody levels in prediabetic children who turned positive for diabetes-associated autoantibodies in a prospective birth cohort study. Methods. Serial serum samples taken during prospective observation starting at birth were analysed for IgG and IgA class antibodies against enterovirus antigens including purified coxsackievirus B4, echovirus 11, poliovirus 1 and a synthetic enterovirus peptide antigen using enzyme immunoassay. Maternal samples taken at the end of the third month of pregnancy were also studied. Analyses were done from 21 childen who developed autoantibodies and from 104 autoantibody-negative control children who were matched for the time of birth, gender and HLA susceptibility alleles. For comparison, adenovirus antibodies were also analysed from all samples collected. Results. IgG class enterovirus antibody levels were high in maternal samples and in cord blood in both case and control children. After birth the IgG levels decreased reaching a nadir at the age of 6 months. No IgA class antibodies were detected at birth but started to emerge postnatally. Antibody levels did not differ between the autoantibody positive and the control children during the first 6 months of life. From 6 months to 24 months of age, the autoantibody positive children had higher IgG and IgA levels against coxsackievirus B4, echovirus 11 and the synthetic enterovirus peptide antigens than control children but poliovirus 1 and adenovirus antibodies were closely similar in the two groups. The difference between children with autoantibodies and control children was predominantly seen among boys and among those with the HLA-DQB1*0302/x genotype. Conclusions/interpretation. Our data show that children who seroconverted for diabetes-associated autoantibodies develop stronger humoral immune responses to coxsackievirus B4, echovirus 11 and a synthetic enterovirus peptide antigen than children who remained negative for autoantibodies. Poliovirus antibodies induced by uniform vaccinations did not differ between the prediabetic and control children suggesting that the regulation of antibody responses to enteroviruses is not disturbed. Accordingly, the results imply a stronger enterovirus exposure in prediabetic children supporting the role of enteroviruses in the pathogenesis of Type I diabetes. [Diabetologia (2001) 44: 818±823]

Analgesic antipyretic use among young children in the TEDDY study: no association with islet autoimmunity

“…Country was included as a stratification factor in the proportional hazards analyses. Additional covariates included in the model were first-degree relative [26], HLA [27], gender, ever breastfed [28, 29], probiotic use prior to 3 months of age [30], and eight different previously identified single nucleotide polymorphisms [31]. The primary variable of interest was cumulative ANAP use through 2.5 years of life as a time dependent covariate.…”

Viruses and Type 1 diabetes: a dynamic labile equilibrium

“…Furthermore, in a recent study, Yeung and colleagues showed that children with islet autoimmunity have higher levels of multiple cytokines, consistent with an active inflammatory process in the prediabetic state, yet these findings were unrelated to coincident EV infection [15]. However, the DIPP study found a close temporal association between the appearance of the first diabetes-associated autoantibodies and EV infections [16,17], and similar results were seen in the TRIGR study [18]. …”

Murine Pancreatic Beta TC3 Cells Show Greater2′,5′-Oligoadenylate Synthetase (2′5′<

“…Somewhat paradoxically, it has also been reported that induction of IFNs in virus-infected beta cells was critical for their survival during viral infection [18, 53]. Increased numbers of enteroviral infections have been reported in prediabetic individuals [2, 4, 54], and recently enteroviruses have been detected in pancreatic tissue from type 1 diabetic patients [6, 22, 23]. Taken together, these findings suggest that pancreatic viral infection may occur before and during onset of clinical diabetes, and that alterations of antiviral defense in virus-infected pancreatic beta cells may influence susceptibility to developing type I diabetes.…”