SCREENING OF NEWBORNS/CHILDREN TO IDENTIFY SUBJECTS AT HIGH RISK FOR IDD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 遗传、免疫和外源性因素相互作用，在一小部分有发生胰岛素依赖型糖尿病(IDDM)遗传易感性的个体中诱导胰岛β细胞自身免疫。我们过去的研究证明，临床前IDDM可以通过免疫和代谢标记物在儿童和成人中发现。他们还证明，在高危个体中，针对β细胞抗原的持续自身抗体的产生几乎总是在研究登记时间之前就开始了。因此，我们假设，自身免疫级联的启动以及最终导致临床疾病的分子和细胞变化，发生在生命的非常早期。因为它在婴儿最早产生自身抗体之前就识别出了贝塔细胞自身免疫的高风险，所以我们的新生儿基因筛查计划为我们提供了有史以来第一次在队列设计中检验这一假设的机会。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Genetic, immunological, and exogenous factors interact to induce pancreatic beta-cells autoimmunity in a small minority of the individuals who have a genetic predisposition to developing insulin-dependent diabetes mellitus (IDDM). Our past studies proved that preclinical IDDM could be identified in children and adults with immune and metabolic markers. They also demonstrated that persistent production of autoantibodies against beta-cell antigens in high-risk individuals almost always commenced prior to the time of study enrollment. We therefore hypothesize that the initiation of the autoimmune cascade and the resultant molecular and cellular changes that culminate in clinical disease, occur in the very early years of life. Because it identifies babies at high risk for Beta-cell autoimmunity prior to their earliest production of autoantibodies, our neonatal genetic screening program provides us with our first chance ever to test the hypothesis in a cohort design.