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.

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

“…However, such data may indicate that the gut virome may be more relevant to T1DM pathoetiology than gut bacteria, which tend to show diversity only after the emergence of T1DM. Enteroviruses are one of the major environmental triggers of childhood-onset T1DM, with recent data indicating that enteroviruses may also be an important trigger in adult-onset T1DM [ 84 ]. Overall, data indicate an interrelatedness of the gut microbiota, metaproteome, and virome that is relevant to T1DM onset, as investigated in young children, with a functional remodeling of the gut microbiota accompanying islet autoimmunity [ 77 ].…”

Immunological and virological triggers of type 1 diabetes: insights and implications

“…One key genetic risk factor for T1D is the presence of specific human leukocyte antigen (HLA) alleles, such as HLA-DR3 and HLA-DR4, which are associated with an increased risk of developing T1D ( 2 ). Environmental factors that have been implicated in the development of T1D include viral infections, such as EVs, rotaviruses, and herpes viruses such as cytomegalovirus ( 3 – 5 ), as well as dietary factors, such as the early introduction of gluten ( 6 ). Mechanistically, T1D is characterized by the activation of autoreactive T cells (the majority of these being CD8 + ) that recognize and attack beta-cells in the pancreas, leading to their destruction and subsequent insulin deficiency ( 7 ).…”