Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study

Cinek, Ondřej; Stene, Lars C.; Kramná, Lenka; Tapia, German; Oikarinen, Sami; Witsø, Elisabet; Rasmussen, Trond; Torjesen, Peter A.; Hyöty, Heikki; Rønningen, Kjersti S.

doi:10.1007/s00125-014-3327-4

Cited by 32 publications

(24 citation statements)

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“…The excess of infections preceded the appearance of autoantibodies, paralleling the findings from our previous prospective studies in the DIPP study, the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) pilot and the Childhood Diabetes in Finland (DiMe) cohorts, in which enterovirus infections were documented by antibody assays and detection of viral RNA from serum [6,9,11,[24][25][26]. In addition, the Norwegian Environmental Triggers of Type 1 Diabetes (MIDIA) study also observed a peak in enterovirus RNA in blood at the time of autoantibody seroconversion [12]. Altogether, these findings suggest that enterovirus infections might play a role in the initiation of the beta cell-damaging process.…”

Section: Discussionsupporting

confidence: 82%

“…The results from such studies have suggested that enterovirus infections, diagnosed by serology or by direct detection of the virus from blood, are associated with the appearance of islet autoantibodies long before clinical diabetes is diagnosed [6,9,11,12]. In contrast, the detection of the virus in stools has not shown such an association [13,14], and in one study in which both blood and rectal swabs were analysed, no association at all was found [15].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…Many previous studies have tried to address this hypothesis by serological, immunohistological, and molecular methods (12,13). However, a direct one-on-one relationship of a viral strain only present in patients with T1D has never been found-the reason could be that viruses trigger diabetes as a hit-and-run event and therefore their traces are often not detectable.…”

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confidence: 99%

Enterovirus Infection and Type 1 Diabetes: Closing in on a Link?

Rodríguez-Calvo

Herrath

2015

Diabetes

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“…One of the most important future tasks is to confirm the risk association between EV infections and T1D in different populations. In addition to the DIPP study this risk association has been found in other prospective studies in Finland and in one study from Norway . However, prospective studies which would have been large enough to evaluate the role of EVs in the initiation of islet autoimmunity with satisfactory statistical power are not available from other countries, and such studies should be carried out to confirm this association in different populations.…”

Section: Discussionmentioning

confidence: 58%

Viruses in type 1 diabetes

2016

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Environmental factors play an important role in the pathogenesis of type 1 diabetes and can determine if a genetically susceptible individual develops the disease. Increasing evidence suggest that among other exogenous agents certain virus infections can contribute to the beta-cell damaging process. Possible viral etiology of type 1 diabetes has been explored extensively but the final proof for causality is still lacking. Currently, the group of enteroviruses (EVs) is considered as the strongest candidate. These viruses have been found in the pancreas of type 1 diabetic patients, and epidemiological studies have shown more EV infections in diabetic patients than in controls. Prospective studies, such as the Type 1 Diabetes Prediction and Prevention (DIPP) study in Finland, are of fundamental importance in the evaluation viral effects as they can cover all stages of the beta-cell damaging process, including those preceding the initiation of the process. DIPP study has carried out the most comprehensive virological analyses ever done in prospective cohorts. This article summarizes the findings from these analyses and discuss them in the context of the existing other knowledge and the prospects for intervention studies with EV vaccines or antiviral drugs.

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Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study

Abstract: Positivity for enterovirus RNA in blood did not predict the later induction of islet autoantibodies, but enterovirus tended to be detected more often at the islet autoantibody seroconversion stage.

Cited by 32 publications

References 24 publications

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

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

Enterovirus Infection and Type 1 Diabetes: Closing in on a Link?

Viruses in type 1 diabetes

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