No abstract

Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions.

Background Both the initiation and maintenance of breastfeeding have been reported to be negatively affected by maternal type 1 diabetes (T1D). Aims To prospectively examine the breastfeeding patterns among mothers with and without T1D participating in a large international randomized infant feeding trial (TRIGR). Design Families with a member affected by T1D and with a newborn infant were invited into the study. Those who had HLA-conferred genetic susceptibility for T1D tested at birth with gestation.> 35 weeks and were healthy were eligible to continue in the trial. Among the 2160 participating children, 1096 were born to women with T1D and 1064 to unaffected women. Information on infant feeding was acquired from the family by frequent prospective dietary interviews. Results Most (>90%) of the infants of mothers with and without T1D were initially breastfed. Breastfeeding rates declined more steeply among mothers with than without T1D being 50% and 72% at 6 months respectively. Mothers with T1D were younger, less educated and delivered earlier and more often by caesarean section than other mothers (p<0.01). After adjusting for all these factors associated with the termination of breastfeeding, there was no difference in the duration of breastfeeding amongst mothers with and without T1D. Conclusions Maternal diabetes status per se was not associated with shorter breast feeding. The lower duration of breastfeeding in mothers with T1D is largely explained by their more frequent caesarean sections, earlier delivery and lower age and education.

The 5-year cumulative incidence of childhood CD is significantly higher in Finland than in Estonia. Sequential infections early in life may increase the risk for developing CD.

The prevalence of immune-mediated diseases, such as allergies and type 1 diabetes, is on the rise in the developed world. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from infants born in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economic conditions). The whole blood transcriptome of Finnish and Estonian neonates differed from their Karelian counterparts, suggesting exposure to toll-like receptor (TLR) ligands and a more matured immune response in infants born in Karelia. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation in accordance with the surrounding microbial milieu.