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，病毒感染一直被假设为儿童自身免疫性疾病的触发因素， 儿童疫苗对预防这类疾病的益处尚不确定。以这些益处为重点的研究 由于美国疫苗推迟接种率的上升和儿科疫苗接种率的下降， 因为新冠疫情 这是一个重新提交的， PA-18741 R21肥胖的次要分析， 糖尿病、消化系统和肾脏疾病。我们的目标是检查麻疹腮腺炎和风疹 MMR疫苗和轮状病毒疫苗可保护儿童免于发生3种相关的自身免疫性疾病 儿童时期的疾病：1型糖尿病（T1 D）、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，我们和其他人报道， 先天性风疹感染会增加T1 D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， 以及训练有素的T细胞反应，从而赋予免疫力，这是多微生物以及保护免受 麻疹、腮腺炎和风疹。因此，MMR可能可以保护自身免疫性疾病的触发因素， 但现有的研究相对较少且力度不足。沿着类似的路线，我们和其他人报告说， RV可能通过干扰分子模拟引起的自身免疫来保护T1 D。之间 对于T1 D高危人群，RV还可预防儿童乳糜泻。不确定RV是否 在广泛人群中预防乳糜泻，以及RV是否能预防自身免疫性甲状腺疾病 疾病为了解决这些知识空白，我们建议检查MMR的保护作用， 儿童T1 D、乳糜泻和自身免疫性甲状腺疾病以及RV乳糜泻， 自身免疫性甲状腺疾病在国家，医疗综合健康保险数据库，我们使用 在我们之前的研究中（n= 1，474，535）。目标1是检查MMR是否可以降低幼儿期的风险 T1 D;我们假设接受MMR的婴儿与未接种疫苗的婴儿相比风险较低。目的 2是检查MMR和RV是否降低儿童早期乳糜泻的风险。我们假设 与未接种疫苗的婴儿相比，接种MMR或RV的婴儿风险较低。目标3：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 与未接种疫苗的婴儿相比，接种MMR或RV的婴儿风险较低。是不道德 进行临床试验，以确定疫苗对自身免疫性疾病的影响，但研究的重点是 自身免疫性疾病的预防能力不足。因此，仔细进行的观察性研究 需要研究疫苗对这些疾病的益处。这些好处可能是一个令人信服的 接种疫苗的动机--犹豫不决。由于我们在流行病学方面的专业知识， 复杂的关系数据，熟悉数据集，我们可以有效地进行这项高影响力的工作。