Virginia Mason/UCHSC Autoimmune Prevention Center

拟议的自身免疫预防中心结合了研究人员的努力和科罗拉多州丹佛市科罗拉多大学健康科学中心(UCHSC)和华盛顿州西雅图的弗吉尼亚州梅森中心(华盛顿大学)的教职员工任命。UCHSC的附属机构包括芭芭拉·戴维斯儿童中心、弗吉尼亚梅森中心和芭芭拉·戴维斯中心/UCHSC，在自身免疫的免疫学领域有着长期的合作努力和互补的专业知识。特别是作为免疫耐受网络一部分的Brian Kotzin和试剂的实验室。Nepom博士正在利用从Barbara Davis中心获得的T细胞克隆来创造四聚体，以识别导致糖尿病的T细胞。艾森巴特博士和格林鲍姆博士是美国国立卫生研究院糖尿病保护性人类白细胞抗原等位基因研究的联合研究员。弗吉尼亚梅森中心和芭芭拉·戴维斯中心即将开始进行霉酚酸酯和IL2受体抗体治疗新发糖尿病的联合临床试验。我们致力于两个机构之间的合作努力，艾森巴特博士将休假，从2001年7月开始在郭氏和Nepom的实验室工作6个月。此外，我们欢迎有机会将合作努力扩展到预防中心网络。预防中心的教职员工来自免疫学、儿科、内科、预防医学系、流行病学和人类医学遗传学计划。在儿科和内科，子专科包括内分泌科、风湿科、临床免疫科、肾脏科、肺科和胃肠科。有独特的临床研究资源和强大的基础科学教师队伍，在许多情况下，有将基础研究和临床研究相结合的记录。对于目前的建议，DAISY儿童糖尿病前瞻性研究为家庭和普通人群中人类自身免疫的研究提供了重要的资源和范例，我们期待着乳糜泻、类风湿性关节炎、多软骨炎和1型糖尿病的联合研究。提出了三个项目。项目1量化和表征了1型糖尿病的T细胞；项目2在DAISY等研究的基础上启动了类风湿性关节炎的研究；项目3分析了婴儿出生后乳糜泻自身免疫的发展。我们还提出了两项初步研究，一项是评估多软骨炎，另一项是在基础动物模型中评估特定信号通路(CD32和磷脂酰丝氨酸受体)在维持耐受和自身免疫发展中的重要性。

The proposed Autoimmunity Prevention Center combines the efforts of investigators with faculty appointments at the University of Colorado Health Sciences Center (UCHSC), Denver Colorado and the Virginia Mason Center (University of Washington) in Seattle Washington. Affiliated institutions at the UCHSC include the Barbara Davis Center for Childhood Virginia Mason Center and the Barbara Davis Center/UCHSC have a long history of collaborative efforts and complementary expertise in the field of immunology of autoimmunity. In particular the laboratories of Brian Kotzin and reagents as part of the Immune Tolerance Network. T cell clones derived at the Barbara Davis Center are being utilized by Dr. Nepom to create tetramers to identify diabetogenic T cells. Drs. Eisenbarth and Greenbaum are co-investigators on an NIH study of diabetes protective HLA alleles. A joint clinical trial of mycophenolate mofetil and IL2 receptor antibodies for new onset diabetes is about to commence at the Virginia Mason Center and the Barbara Davis Center. We are committed to a collaborative effort between the two institutions, with Dr. Eisenbarth going on sabbatical to work in the laboratories of Kwok and Nepom for 6 months beginning in July of 2001. In addition, we welcome the opportunity to extend collaborative efforts to a prevention Center Network. Faculty for the Prevention Center have been recruited from the Departments of Immunology, Pediatrics, Medicine, and Preventive Medicine, Epidemiology, and the Human Medical Genetics Program. Within the Departments of Pediatrics and Medicine, subspecialties include endocrinology, rheumatology, clinical immunology, nephrology, pulmonary, and gastroenterology. There are unique resources for clinical investigation and strong basic science faculty and in many instances a track record for combining basic and clinical investigation. For the current proposal, the DAISY prospective study of children developing diabetes provides an essential resource and paradigm for the study of human autoimmunity in families and the general population and we are looking forward to joint studies of celiac disease, rheumatoid arthritis, polychondritis, and type 1 diabetes. Three Projects are proposed. Project 1 Quantitate and Characterize T cells of Type 1 diabetes; Project 2 Initiate studies of rheumatoid arthritis modeled on studies such as DAISY; Project 3 Analyze the development of celiac disease autoimmunity of infants followed from birth. Two Pilot studies are also proposed, one evaluating polychondritis and the other evaluating in basic animal models the importance of specific signaling pathways (CD32 and phosphatidylserine receptor) to maintenance of tolerance and development of autoimmunity.