Virginia Mason/UCHSC Autoimmune Prevention Center

拟建的自身免疫预防中心将研究人员的努力与科罗拉多州丹佛市科罗拉多大学健康科学中心（UCHSC）和华盛顿州西雅图市弗吉尼亚梅森中心（华盛顿大学）的教职人员结合起来。加州大学圣迭戈分校的附属机构包括芭芭拉·戴维斯儿童弗吉尼亚梅森中心和芭芭拉·戴维斯中心/加州大学圣迭戈分校在自身免疫免疫学领域有着悠久的合作历史和互补的专业知识。特别是Brian Kotzin的实验室和试剂作为免疫耐受网络的一部分。从芭芭拉戴维斯中心获得的T细胞克隆正被Nepom博士用于制造四聚体，以识别致糖尿病的T细胞。Drs。Eisenbarth和Greenbaum是NIH糖尿病保护HLA等位基因研究的共同研究者。一项霉酚酸酯和il - 2受体抗体治疗新发糖尿病的联合临床试验即将在弗吉尼亚梅森中心和芭芭拉戴维斯中心开始。我们致力于两个机构之间的合作，从2001年7月开始，Eisenbarth博士将休假到Kwok和Nepom实验室工作6个月。此外，我们欢迎有机会将合作努力扩大到预防中心网络。预防中心的教职员工来自免疫学、儿科、医学、预防医学、流行病学和人类医学遗传学项目。在儿科和医学部，亚专科包括内分泌学、风湿病学、临床免疫学、肾脏病学、肺病学和胃肠病学。有独特的临床研究资源和强大的基础科学师资队伍，在许多情况下，有将基础研究和临床研究结合起来的记录。就目前的提案而言，DAISY对儿童糖尿病的前瞻性研究为家庭和普通人群的人类自身免疫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。项目一：1型糖尿病患者T细胞的定量与表征；启动以DAISY等研究为模型的类风湿关节炎研究；项目三：分析婴儿出生后乳糜泻自身免疫的发展情况。两项初步研究也被提出，一项评估多软骨炎，另一项在基本动物模型中评估特定信号通路（CD32和磷脂酰丝氨酸受体）对维持耐受性和自身免疫发展的重要性。

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.