Diabetes Perdiction in Skane(DiPiS)

描述(由申请人提供)： 1型糖尿病(T1 DM)发生在遗传易感人群中。环境因素与疾病有很强的相关性，环境因素被认为是引发疾病的原因。该病的发病机制依赖于自身免疫现象，包括针对β细胞中几种自身抗原的细胞和体液免疫反应。这种疾病有很长的前驱症状，GAD65、IA-2或胰岛素自身抗体的出现预示着疾病的发生。在这项名为糖尿病预测(DiPiS)的研究中，我们将筛查所有新生儿(每年约10,000名儿童)的高危人类白细胞抗原和其他TIDM遗传因素。针对GAD65、IA-2和胰岛素的胰岛细胞自身抗体将在出生时和随访期间进行分析，以确定环境触发因素。特别是，我们将测试这一假设，即妊娠不良事件代表胰岛自身免疫的触发因素，将进展为1型糖尿病，但仅在一些易感受试者中。其具体目标是：1)对瑞典南部斯堪市120万居民的所有新生儿进行筛查；2)分析脐带血中1型糖尿病高危人类白细胞抗原等位基因和三种胰岛细胞自身抗体GAD65Ab、IAA和IA-2Ab；3)分析感染史、妊娠不良事件和心理社会因素作为1型糖尿病风险的附加或增强因素，以及孕期病毒聚合酶链式反应和血清学；4)确定出生时、首次出现自身抗体和诊断1型糖尿病时GAD65、IA-2和胰岛素自身抗体的同型、亚型和表位特异性；5)确定自身抗体阳性的健康母亲所生新生儿中的自身抗原反应性T细胞，作为自身免疫暴露的证据；6)向数据协调中心(DCC)提交关键数据，以有效地识别1型糖尿病的环境诱因。长期目标是确定妊娠感染或其他不良事件和心理因素在遗传易感儿童中增加1型糖尿病风险的作用。了解遗传风险和环境风险因素之间的相互作用可能有助于制定减少暴露的策略，从而将糖尿病风险降至最低。

DESCRIPTION (provided by applicant): Type 1 diabetes mellitus (T1DM) develops in genetically susceptible individuals. There is a strong disease association with environmental factors, which are thought to trigger the disease. The disease pathogenesis is dependent on autoimmune phenomena involving both the cellular and humoral immune response direct against several autoantigens in the beta cells. The disease has a long prodrome and the appearance of GAD65, IA-2 or insulin autoantibodies predict disease. In the present study - Diabetes Prediction in Skane (DiPiS) we will screen all newborns (about 10, 000 children per year) for high risk HLA and other TIDM genetic factors. Islet cell autoantibodies against GAD65, IA-2 and insulin will be analyzed at birth and during follow-up to identify environmental triggers. In particular, we will test the hypothesis that gestational adverse events represents triggers of islet autoimmunity that will progress to type 1 diabetes but only in some susceptible subjects. The Specific aims are: 1) to screen all newborn babies in Skane, the southern region of Sweden with 1.2 million inhabitants; 2) to analyze the cord blood for type 1 diabetes high risk HLA alleles and for the three islet cell autoantibodies, GAD65Ab, IAA and IA-2Ab; 3) to analyze infectious history, gestational adverse events and psychosocial factors as additive or potentiating factors to type 1 diabetes risk along with virus PCR and serology during pregnancy; 4) to define isotype, subtype and epitope specificities of autoantibodies to GAD65, IA-2 and insulin at birth, at the first appearance of autoantibodies and at diagnosis of type 1 diabetes; 5) to determine autoantigen reactive T cells in neonates born to healthy mothers positive for autoantibodies as evidence of autoimmunity exposure and 6) to submit critical data to the Data Coordinating Center (DCC) to effectively identify environmental triggers of type 1 diabetes. The long-term objective is to identify the role of gestational infections or other adverse events and psychological factors that increase the risk for type 1 diabetes in genetically susceptible children. Understanding the interaction between genetic risk and environmental risk factors may permit the development of strategies to reduced exposure and thereby minimize diabetes risk.