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Diabetologia
Published in: Diabetologia 5/2018

01-05-2018 | Article

Coxsackievirus B1 infections are associated with the initiation of insulin-driven autoimmunity that progresses to type 1 diabetes

Authors: Amir-Babak Sioofy-Khojine, Jussi Lehtonen, Noora Nurminen, Olli H. Laitinen, Sami Oikarinen, Heini Huhtala, Outi Pakkanen, Tanja Ruokoranta, Minna M. Hankaniemi, Jorma Toppari, Mari Vähä-Mäkilä, Jorma Ilonen, Riitta Veijola, Mikael Knip, Heikki Hyöty

Published in: Diabetologia | Issue 5/2018

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Abstract

Aims/hypothesis

Islet autoimmunity usually starts with the appearance of autoantibodies against either insulin (IAA) or GAD65 (GADA). This categorises children with preclinical type 1 diabetes into two immune phenotypes, which differ in their genetic background and may have different aetiology. The aim was to study whether Coxsackievirus group B (CVB) infections, which have been linked to the initiation of islet autoimmunity, are associated with either of these two phenotypes in children with HLA-conferred susceptibility to type 1 diabetes.

Methods

All samples were from children in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study. Individuals are recruited to the DIPP study from the general population of new-born infants who carry defined HLA genotypes associated with susceptibility to type 1 diabetes. Our study cohort included 91 children who developed IAA and 78 children who developed GADA as their first appearing single autoantibody and remained persistently seropositive for islet autoantibodies, along with 181 and 151 individually matched autoantibody negative control children, respectively. Seroconversion to positivity for neutralising antibodies was detected as the surrogate marker of CVB infections in serial follow-up serum samples collected before and at the appearance of islet autoantibodies in each individual.

Results

CVB1 infections were associated with the appearance of IAA as the first autoantibody (OR 2.4 [95% CI 1.4, 4.2], corrected p = 0.018). CVB5 infection also tended to be associated with the appearance of IAA, however, this did not reach statistical significance (OR 2.3, [0.7, 7.5], p = 0.163); no other CVB types were associated with increased risk of IAA. Children who had signs of a CVB1 infection either alone or prior to infections by other CVBs were at the highest risk for developing IAA (OR 5.3 [95% CI 2.4, 11.7], p < 0.001). None of the CVBs were associated with the appearance of GADA.

Conclusions/interpretation

CVB1 infections may contribute to the initiation of islet autoimmunity being particularly important in the insulin-driven autoimmune process.
Appendix
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Metadata
Title
Coxsackievirus B1 infections are associated with the initiation of insulin-driven autoimmunity that progresses to type 1 diabetes
Authors
Amir-Babak Sioofy-Khojine
Jussi Lehtonen
Noora Nurminen
Olli H. Laitinen
Sami Oikarinen
Heini Huhtala
Outi Pakkanen
Tanja Ruokoranta
Minna M. Hankaniemi
Jorma Toppari
Mari Vähä-Mäkilä
Jorma Ilonen
Riitta Veijola
Mikael Knip
Heikki Hyöty
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 5/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4561-y

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