IgA-Type Enterovirus Antibodies Are Increased among Adults and Children with Recently Diagnosed Type 1 Diabetes

Abstract

Enteroviruses (EV) are among the leading environmental triggers of childhood-onset type 1 diabetes (T1D). Our aim was to determine the prevalence of antibodies against EV and their association with T1D in different age groups (n = 62), including young adults, and to compare these data with results from HLA-matched control participants (n = 62). IgA, IgG, and IgM antibodies against EV were detected. IgA EV antibodies were present in 46.8% of participants with T1D (median level 10.9 EIU) and in 11.3% of controls (median level 3.4 EIU). IgA EV positivity and higher level of IgA EV antibodies were both significant risk factors for T1D (odds ratio (OR) 8.33; 95% confidence interval (CI) 2.52-27.6; p = 0.0005 and OR 1.04; 95% CI 1.01-1.06; p = 0.0105, respectively). Importantly, the prevalence of IgA EV antibodies in the subgroups of both children and young adults was also significantly different between participants with T1D and their matched controls (p = 0.0089 and p = 0.0055, respectively). Such differences were not seen for IgG and IgM EV antibodies. However, IgG EV antibodies were associated with 65 kDa glutamic acid decarboxylase antibodies, but not with zinc transporter 8 and protein tyrosine phosphatase IA2 antibodies. The genotype frequency of PTPN22 (rs2476601) and IFIH1 (rs1990760) was not associated with EV positivity. This study showed that EV infections may be an important disease-promoting factor of T1D not only in childhood-onset but also in adult-onset T1D. However, to further confirm this association, direct virological studies are needed in the latter T1D group.

Figure 1

Differences in (a) IgA and (b) IgG enterovirus (EV) antibody levels between participants with T1D and controls. ^∗Conditional logistic regression model: matched odds ratio for gender, age, and HLA-DR/DQ genotype risk groups for T1D with the 95% confidence interval (CI). p values ≤ 0.05 were considered significant.

Figure 2

Differences in IgA enterovirus (EV) antibody level between participants with T1D and controls by the age groups (a) 0-18.9 years of age and (b) 19-35.9 years of age. ^∗Conditional logistic regression model: matched odds ratio for gender, age, and HLA-DR/DQ genotype risk groups for T1D with the 95% confidence interval (CI). p values ≤ 0.05 were considered significant.