Beneficial effects of childhood vaccines for prevention of type 1 diabetes, autoimmune thyroid disease, and celiac disease

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Viral infections have long been hypothesized to be triggers for childhood autoimmune conditions, but the benefit of childhood vaccines for prevention of such diseases is uncertain. Studies focusing upon such benefits are critical due to the rising rates of vaccine deferral in the U.S and the lowered rates of pediatric vaccination due to the COVID pandemic. This is a resubmission for PA-18741 R21 Secondary Analyses in Obesity, Diabetes and Digestive and Kidney Diseases. Our goal is to examine whether measles, mumps, and rubella vaccine (MMR) and rotavirus vaccine (RV) protect children from developing 3 associated autoimmune diseases during childhood: type 1 diabetes (T1D), celiac disease, and autoimmune thyroid disease. Congenital rubella increases pancreatic islet cell autoantibody production, and we and others have reported that congenital rubella infection increases risk for T1D. Congenital rubella infection is also associated with anti- thyroglobulin antibody, a precursor of autoimmune thyroid disease. MMR appears to induce heterologous as well as trained T-cell responses, thus conferring immunity that is polymicrobial as well as protection against measles, mumps, and rubella. Therefore, MMR may plausibly protect against triggers for autoimmune disease, but existing studies are relatively few and underpowered. Along similar lines, we and others have reported that RV protects against T1D, possibly by interfering with auto-immunization caused by molecular mimicry. Among persons at high risk for T1D, RV also protects against childhood celiac disease. It is uncertain whether RV protects against celiac disease in a broad population, and whether RV protects against autoimmune thyroid disease. To address these knowledge gaps, we propose to examine the protective effects of MMR for childhood T1D, celiac disease, and autoimmune thyroid disease as well as RV for celiac disease and autoimmune thyroid disease in the national, longitudinally-integrated health insurance database that we used in our previous studies (n=1,474,535). Aim 1 is to examine whether MMR decreases risk of early childhood T1D; we hypothesize that infants who receive MMR will have lower risk compared to unvaccinated infants. Aim 2 is to examine whether MMR and RV decrease risk of early childhood celiac disease. We hypothesize that infants who receive MMR or RV will have lower risk compared to unvaccinated infants. Aim 3 is to examine whether MMR and RV decrease risk of early childhood autoimmune thyroid disease. We hypothesize that infants who receive MMR or RV will have lower risk compared to unvaccinated infants. It is unethical to conduct clinical trials to establish the impact of vaccines upon autoimmune disease, but studies focusing upon autoimmune disease prevention are under-powered. Therefore, carefully conducted observational studies are needed which examine the benefits of vaccines for such diseases. Such benefits may prove to be a compelling motivator to vaccinate for the vaccine-hesitant. Due to our expertise in epidemiology, statistical analysis of complex relational data, and familiarity with the datasets, we can efficiently conduct this high-impact work.