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

儿童疫苗对预防 1 型糖尿病、自身免疫性甲状腺疾病和乳糜泻的有益作用

• 批准号: 10482378
• 负责人: CATHERINE KIM
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-06 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10482378
• 关键词: Acute; Address; Affect; Autoantibodies; Autoimmune Diseases; Autoimmunity; COVID-19 pandemic; Celiac Disease; Child; Childhood; Childhood diabetes; Chronic; Chronic Disease; Clinical Trials; Complex; Conduct Clinical Trials; Congenital Rubella Syndrome; Data; Data Set; Databases; Diabetes Mellitus; Digestive System Disorders; Disease; Enrollment; Ensure; Epidemiology; Familiarity; Goals; Hashimoto Disease; Health Insurance; Immune response; Immunity; Immunization; Incidence; Infant; Infection; Insulin-Dependent Diabetes Mellitus; Insurance; Insurance Coverage; Islet Cell; Islets of Langerhans; Kidney Diseases; Knowledge; Laboratories; Measles; Measles Vaccine; Measles-Mumps-Rubella Vaccine; Mediating; Molecular Mimicry; Mumps; Natural Immunity; Obesity; Observational Study; Parents; Persons; Pharmaceutical Preparations; Population; Prevention; Preventive measure; Production; Reporting; Risk; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Rubella; Statistical Data Interpretation; Structure of beta Cell of islet; T cell response; T memory cell; T-Lymphocyte Epitopes; Testing; Thyroglobulin antibody; Training; United States; Vaccinated; Vaccination; Vaccines; Virus Diseases; Visit; Work; autoimmune thyroid disease; disorder prevention; early childhood; high risk; large datasets; prevent; protective effect; response; risk minimization; safety study; secondary analysis; stem; unethical; unvaccinated; vaccine hesitancy; vaccine refusal; vaccine safety; vaccine trial

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.

长期以来，病毒感染一直是儿童自身免疫性疾病的触发因素，但 儿童期疫苗预防这种疾病的益处尚不确定。研究重点的研究 由于美国递延疫苗递延率的上升和小儿疫苗接种率降低而至关重要 由于共同的大流行。 这是重新提交的 PA-18741 R21肥胖中的次要分析， 糖尿病，消化和肾脏疾病。我们的目标是检查麻疹，腮腺和风疹是否 疫苗（MMR）和轮状病毒疫苗（RV）保护儿童免受3种相关的自身免疫性 儿童期疾病：1型糖尿病（T1D），乳糜泻和自身免疫性甲状腺疾病。先天性 风疹增加胰岛细胞自身抗体的产生，我们和其他人报告说 先天性风疹感染增加了T1D的风险。先天性风疹感染也与 甲状腺球蛋白抗体，自身免疫性甲状腺疾病的前体。 MMR似乎诱导异源 以及受过训练的T细胞反应，因此赋予多数菌和保护的免疫力 麻疹，腮腺炎和风疹。因此，MMR可能可能预防自身免疫性疾病的触发因素， 但是现有的研究相对较少且功能不足。同样，我们和其他人报告说 RV可以通过干扰分子模仿引起的自身免疫来预防T1D。之中 RV患有T1D高风险的人也可以防止儿童腹腔疾病。不确定RV是否 在广泛人群中预防腹腔疾病，以及RV是否可以防止自身免疫性甲状腺 疾病。为了解决这些知识差距，我们建议检查MMR的保护作用 儿童时期T1D，乳糜泻和自身免疫性甲状腺疾病以及乳糜泻的RV 我们使用的国家纵向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）。目标1是检查MMR是否降低了幼儿的风险 t1d;我们假设与未接种疫苗的婴儿相比，接受MMR的婴儿的风险将较低。目的 2是检查MMR和RV是否会降低儿童早期腹腔疾病的风险。我们假设这一点 与未接种疫苗的婴儿相比，接受MMR或RV的婴儿的风险较低。目标3是检查 MMR和RV是否会降低儿童早期自身免疫性甲状腺疾病的风险。我们假设这一点 与未接种疫苗的婴儿相比，接受MMR或RV的婴儿的风险较低。这是不道德的 进行临床试验以确立疫苗对自身免疫性疾病的影响 预防自身免疫性疾病的动力不足。因此，经过精心进行的观察性研究是 需要检查疫苗对此类疾病的好处。这种好处可能被证明是一个引人注目的 为疫苗疫苗接种疫苗的动力。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，我们可以有效地进行这项高影响力的工作。