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

长期以来，病毒感染一直被认为是儿童自身免疫疾病的触发因素，但 儿童疫苗对预防此类疾病的益处尚不确定。关注这些益处的研究 由于美国疫苗延期接种率的上升和儿童疫苗接种率的下降，这两个因素至关重要 由于新冠状病毒大流行。 这是重新提交给 PA-18741 R21在肥胖中的二级分析， 糖尿病与消化和肾脏疾病。我们的目标是检查麻疹、腮腺炎和风疹 疫苗(MMR)和轮状病毒疫苗(RV)保护儿童免受相关自身免疫的影响 儿童时期的疾病：1型糖尿病(T1D)、乳糜泻和自身免疫性甲状腺疾病。先天 风疹可增加胰岛细胞自身抗体的产生，我们和其他人已经报告了 先天性风疹感染增加了患T1D的风险。先天性风疹感染也与抗- 甲状腺球蛋白抗体，自身免疫性甲状腺疾病的前兆。MMR似乎诱导异源AS 以及训练有素的T细胞反应，从而产生多种微生物的免疫力，并防止 麻疹、腮腺炎和风疹。因此，MMR似乎可以预防自身免疫性疾病的触发， 但现有的研究相对较少，动力不足。按照类似的思路，我们和其他人已经报告了 轮状病毒对T1D有保护作用，可能是通过干扰分子模仿引起的自身免疫。其中 T1D的高危人群，RV还可以预防儿童乳糜泻。目前还不确定房车是否 在广大人群中预防乳糜泻，以及轮状病毒是否预防自身免疫性甲状腺 疾病。为了解决这些知识差距，我们建议研究MMR对 儿童T1D、乳糜泻和自身免疫性甲状腺疾病，以及乳糜泻和乳糜泻的RV 我们使用的全国性纵向综合健康保险数据库中的自身免疫性甲状腺疾病 在我们以前的研究中(n=1,474,535)。目的1是检查MMR是否能降低儿童早期患病的风险 T1D；我们假设，与未接种疫苗的婴儿相比，接受MMR的婴儿风险较低。目标 二是检查MMR和RV是否降低了儿童早期乳糜泻的风险。我们假设 接种MMR或RV的婴儿与未接种疫苗的婴儿相比，风险较低。目标3是检查 MMR和RV是否降低儿童早期自身免疫性甲状腺疾病的风险。我们假设 接种MMR或RV的婴儿与未接种疫苗的婴儿相比，风险较低。这样做是不道德的 进行临床试验以确定疫苗对自身免疫性疾病的影响，但研究重点是 自身免疫性疾病的预防力度不足。因此，仔细进行的观察性研究是 需要审查疫苗对这类疾病的益处。这些好处可能被证明是一种令人信服的 接种疫苗的动力--犹豫不决。由于我们在流行病学方面的专业知识，统计分析 复杂的关系数据，以及对数据集的熟悉，我们可以高效地进行这项高影响的工作。

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.