A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes.

OnlinePublAims/Introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically atrisk for type 1 diabetes followed from birth who had developed islet autoantibodies (“seroconverted”), by measuring mucosa-associated cytokines in their sera. Materials and Methods: Sera were collected 3 monthly from birth from children with a first-degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results: Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosaassociated cytokines IL-21, IL-22, IL-25, and IL-10, the Th17-related cytokines IL-17F and IL23, as well as IL-33, IFN-c, and IL-4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex- and age-matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions: In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa-associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity.Leonard C Harrison, Esther Bandala-Sanchez, Helena Oakey, Peter G Colman, Kelly Watson, Ki Wook Kim, Roy Wu, Emma E Hamilton-Williams, Natalie L Stone, Aveni Haynes, Rebecca L Thomson, Peter J Vuillermin, Georgia Soldatos, William D Rawlinson, Kelly J McGorm, Grant Morahan, Simon C Barry, Richard O Sinnott, John M Wentworth, Jennifer J Couper, Megan AS Penno, on behalf of the ENDIA Study Grou