Coxsackievirus B1 Infections Are Associated with the Initiation of Insulin-driven Autoimmunity That Progresses to Type 1 Diabetes

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2018 Feb 7

PMID 29404673

Citations 58

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 Vaha-Makila

Jorma Ilonen

Riitta Veijola

Mikael Knip

Heikki Hyoty

Affiliations

Soon will be listed here.

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.

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