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

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.

Enterovirus infections in young infants: are children still protected by maternal antibodies?

Enterovirus infections are frequent in childhood and may be involved in development of several chronic diseases including type 1 diabetes. Maternal antibodies have a protective effect in young infants. It has been proposed that this protection is now vanishing due to decreasing circulation of enteroviruses in Western countries. We aimed to analyse the occurrence of enterovirus infections in 55 infants and to assess the protection provided by maternal antibodies to these children and the development of enterovirus antibodies in a prospective cohort study. In addition, the presence of enteroviruses was detected in faeces using RT-PCR and their serotype identified using VP1 region sequencing. Our results showed that before polio vaccination 12 of 194 faecal samples were positive for enterovirus RNA (coxsackieviruses A4, A5, A16 or echoviruses 13 and 16). After vaccination Sabin 1, 2 and 3 poliovirus strains predominated in stool samples. From birth to 6 months of age polio IgG and IgA increased in most of children whereas the levels of other enterovirus antibodies started to increase from 6 months to 24 months age. The frequency of maternal neutralizing antibodies was generally quite high but still 3 out of 8 infants had no maternal antibodies against the enterovirus serotype which they had in stool sample. This study shows that enterovirus infections are relatively frequent already before the age of 3 months. Considerable proportion of infants lack maternal antibodies against the virus causing their infection. The significance of this phenomenon needs to be evaluated in larger studies.

Demonstration of high prevalence of SS-A antibodies in a general population: association with HLA-DR and enterovirus antibodies.

Autoantibodies are helpful markers for diagnosing autoimmune diseases and there is a link between HLA-DR3 and the prevalence of SS-A antibodies in clinical groups. We aimed to study this association at the level of general adult population and to verify whether these antibodies are more common in persons with antibodies against enteroviruses as possible associates of Sjögren syndrome. The studied material included sera from 200 persons, randomly selected from a general population sample. The IgG type of SS-A/SS-B autoantibodies were measured by nuclear immunoblot, developed by us, and the results were compared to other results obtained by anti-SS-A immunoblot and ELISA. Enterovirus antibodies were detected by ELISA using common enterovirus antigenic peptide KEVPALTAVETGAT. Altogether 33 out of 200 sera showed SS-A and/or SS-B bands in immunoblot, including all seven ANA Profile 3 (Euroimmune) positive sera. One of the persons positive in these two tests showed also positive reaction on anti-SS-A ELISA (Euroimmune). None of the antibody-positive persons had Sjögren's syndrome or other rheumatic disease. Among 82 HLA typed persons, selected at random, the HLA-DRB1*03 and HLA-DRB1*11 allele carriers included significantly more persons with SS-A antibodies than the non-carries (p = 0.008). Antibodies against enterovirus peptide were present more frequently in persons with SS-A autoantibodies than in age- and sex-matched controls (p = 0.009). Summing up, our study showed that the prevalence of SS-A/SS-B antibodies in a general random population might be higher than thought previously being detected in up to 16.5% of persons including a significant number of those with HLA-DR3 or/and DR11 alleles and with antibodies against enteroviruses. Whether all these persons have the risk of developing rheumatic diseases should be evaluated by follow up studies.