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，病毒感染一直被认为是儿童自身免疫性疾病的诱因，但 儿童疫苗对于预防此类疾病的益处尚不确定。研究重点关注这些好处 由于美国疫苗接种推迟率上升以及儿童疫苗接种率下降，这一点至关重要 由于新冠肺炎大流行。 这是重新提交 PA-18741 R21 肥胖的二次分析， 糖尿病、消化系统疾病和肾脏疾病。我们的目标是检查麻疹、腮腺炎和风疹是否 疫苗 (MMR) 和轮状病毒疫苗 (RV) 可保护儿童免受 3 种相关自身免疫性疾病的影响 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 风疹会增加胰岛细胞自身抗体的产生，我们和其他人已经报道过 先天性风疹感染会增加患 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 似乎会诱导异源性 以及训练有素的 T 细胞反应，从而赋予多种微生物的免疫力以及针对 麻疹、腮腺炎和风疹。因此，MMR 可能可以预防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够。沿着类似的思路，我们和其他人报告说 RV 可能通过干扰分子拟态引起的自身免疫来预防 T1D。之中 对于 T1D 高危人群，RV 还可以预防儿童乳糜泻。 RV是否还不确定 预防广大人群的乳糜泻，以及 RV 是否可以预防自身免疫性甲状腺 疾病。为了解决这些知识差距，我们建议检查 MMR 对 儿童 T1D、乳糜泻和自身免疫性甲状腺疾病以及 RV 治疗乳糜泻和 我们使用的国家纵向整合健康保险数据库中的自身免疫性甲状腺疾病 在我们之前的研究中（n=1,474,535）。目标 1 是检查 MMR 是否会降低幼儿期风险 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，接受 MMR 或 RV 的婴儿的风险较低。目标 3 是检查 MMR 和 RV 是否可以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 自身免疫性疾病预防力度不足。因此，仔细进行观察性研究 需要检查疫苗对此类疾病的益处。这些好处可能会被证明是令人信服的 对疫苗犹豫不决的人接种疫苗的动机。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，我们可以有效地开展这项高影响力的工作。