Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity

Abstract

Aims/hypothesis This case-control study was nested in a prospective birth cohort to evaluate whether the presence of enteroviruses in stools was associated with the appearance of islet autoimmunity in the Type 1 Diabetes Prediction and Prevention study in Finland. Methods Altogether, 1673 longitudinal stool samples from 129 case children who turned positive for multiple islet autoantibodies and 3108 stool samples from 282 matched control children were screened for the presence of enterovirus RNA using RT-PCR. Viral genotype was detected by sequencing.Results Case children had more enterovirus infections than control children (0.8 vs 0.6 infections per child). Timedependent analysis indicated that this excess of infections occurred more than 1 year before the first detection of islet autoantibodies (6.3 vs 2.1 infections per 10 follow-up years). No such difference was seen in infections occurring less than 1 year before islet autoantibody seroconversion or after seroconversion. The most frequent enterovirus types included coxsackievirus A4 (28% of genotyped viruses), coxsackievirus A2 (14%) and coxsackievirus A16 (11%). Conclusions/interpretationThe results suggest that enterovirus infections diagnosed by detecting viral RNA in stools are Electronic supplementary material The online version of this article

Live attenuated enterovirus vaccine (OPV) is not associated with islet autoimmunity in children with genetic susceptibility to type 1 diabetes: prospective cohort study

“…The close anatomical location of the pancreas and common lymphatic and vascular Time to the first islet autoantibody (years) The results of the present study clearly show that sequential exposure to OPV significantly increased the detection of enterovirus RNA in stool samples. The rate of enterovirus positivity in stool samples in the IPV group was well in line with our earlier findings in Finnish children [24]. When compared with the IPV group, the children vaccinated with OPV had almost four times more enterovirus-positive stool samples at the age when OPV was administered (< 1 year of age) and this excess was due to increased detection of polioviruses.…”

Association between Field Liming and the Epidemic of Type 1 Diabetes

“…Enterovirus infection before the age of six months seems to be especially dangerous and also after the age of two years. [2] Lysosomal dysfunction also increase antigen abundance. Lysosomes clean a cell from dysfunctional cytoplasmic organelles and damaged proteins by hydrolytic enzymes.…”

“…[1] About twelve per cent of newborns in Finnish DIPP study carried HLA II susceptibility genes for T1D. [2] The incidence of T1D has increased since 1950's. Before 1950's T1D was uncommon but known disease, the incidence of which was some 2-7/100,000/year (in the sequel the incidence numbers are always per 100,000 per year).…”

Maternal virus infections in pregnancy and type 1 diabetes in their offspring: Systematic review and meta‐analysis of observational studies

“…Support for a pathogenic role for viruses in the development of type 1 diabetes is evidenced by space‐time clustering of season at birth and type 1 diabetes diagnosis, the increased incidence of type 1 diabetes following enterovirus (EV) epidemics and the detection of EV RNA in pancreatic biopsies of adults with recent onset type 1 diabetes . EVs have been examined most extensively and have exhibited the strongest association with type 1 diabetes . However, an unequivocal causal link has yet to be established.…”