Denver Autoimmunity Center of Excellence

丹佛自身免疫卓越中心

• 批准号: 6685600
• 负责人: Brian L Kotzin
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-28 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6685600
• 关键词: autoimmune disorder; autoimmunity; clinical research; cooperative study; human subject

DESCRIPTION (provided by applicant): The Denver Autoimmunity Center of Excellence (ACE) aims to bring together basic and clinical investigators for the study of autoimmune diseases. Projects goals focus on defining susceptibility genes, elucidating immunopathogenesis, developing new therapies, accomplishing clinical trials with novel immunotherapeutic agents, and developing tools to better track new therapies in autoimmune disease. The Denver ACE combines the efforts of investigators with faculty appointments at the University of Colorado Health Sciences Center with affiliations with the Barbara Davis Center for Childhood Diabetes, the National Jewish Medical and Research Center, the University of Nebraska Medical Center, hospitals in Denver, the Rocky Mountain Multiple Sclerosis Center, and the Denver Arthritis Clinic. Faculty has been recruited from multiple departments and programs, and the subspecialties of endocrinology, rheumatology, clinical immunology, nephrology, genetics, dermatology, pulmonary, and gastroenterology. There are unique resources for clinical investigation and strong basic science faculty, and a track record for combining basic and clinical investigation. Another major strength of the current proposal is the breadth of work in Denver studying T cell recognition and biology, genetics, and the biology of inflammatory and cytokine mediators. One unique clinical resource relates to ongoing programs to identify individuals who are at high risk to develop type 1 diabetes. In the current application, three proposed basic projects are 1) to define the non-MHC genetic contributions to a distinct subset of human multiple autoimmune disease syndrome, which appears to be inherited as an autosomal dominant trait with high penetrance; (2) to define the role of complement receptors and complement activation in the immunopathogenesis of type 1 diabetes in the NOD mouse model; and (3) to determine the role of type 1 interferons in the pathogenesis of lupus in an animal model, and whether inhibition of the action of these cytokines can prevent and suppress disease expression. In the current proposal, we also describe the multiple groups pursuing clinical investigation of autoimmune disease relevant to the Centers of Excellence. In addition to clinical trials in lupus and lupus nephritis, two new clinical trials are proposed in this application. Both are Phase II, randomized, double blind, and placebo-controlled in patients early in the disease process. Clinical Project 1 investigates the use of a B9-23 altered peptide ligand to prevent the development of clinical disease in patients with pre-diabetes. Clinical project 2 involves the use of a B cell specific monoclonal antibody to CD20 in the treatment of patients with early rheumatoid arthritis (RA). This latter project involves a newly established collaboration with a separate institution and group of clinicians skilled in the clinical investigation of RA.

描述（由申请人提供）： 丹佛自身免疫卓越中心 (ACE) 旨在汇集基础和临床研究人员来研究自身免疫性疾病。项目目标侧重于定义易感基因、阐明免疫发病机制、开发新疗法、完成新型免疫治疗药物的临床试验，以及开发更好地追踪自身免疫性疾病新疗法的工具。丹佛 ACE 将研究人员的努力与科罗拉多大学健康科学中心的教职人员任命结合起来，该中心隶属于芭芭拉·戴维斯儿童糖尿病中心、国家犹太医学研究中心、内布拉斯加大学医学中心、丹佛的医院、落基山多发性硬化症中心和丹佛关节炎诊所。教职员工来自多个科室和项目，以及内分泌学、风湿病学、临床免疫学、肾病学、遗传学、皮肤病学、肺病学和胃肠病学等亚专业。拥有独特的临床研究资源和强大的基础科学师资力量，以及基础与临床研究相结合的良好记录。 当前提案的另一个主要优势是丹佛研究 T 细胞识别和生物学、遗传学以及炎症和细胞因子介质生物学的广泛工作。一项独特的临床资源涉及正在进行的项目，该项目旨在识别患有 1 型糖尿病高风险的个体。在当前的申请中，提出了三个基本项目：1）定义非 MHC 遗传对人类多种自身免疫性疾病综合征的一个独特子集的贡献，该子集似乎是作为具有高外显率的常染色体显性性状遗传的； (2) 在NOD小鼠模型中明确补体受体和补体激活在1型糖尿病免疫发病机制中的作用； (3) 在动物模型中确定 1 型干扰素在狼疮发病机制中的作用，以及抑制这些细胞因子的作用是否可以预防和抑制疾病的表达。在当前的提案中，我们还描述了从事与卓越中心相关的自身免疫性疾病临床研究的多个小组。除了狼疮和狼疮性肾炎的临床试验外，本申请还提出了两项​​新的临床试验。两者均处于疾病早期患者的 II 期、随机、双盲和安慰剂对照试验中。 临床项目 1 研究使用 B9-23 改变的肽配体预防糖尿病前期患者发生临床疾病。临床项目2涉及使用针对CD20的B细胞特异性单克隆抗体治疗早期类风湿性关节炎（RA）患者。后一个项目涉及与擅长 RA 临床研究的独立机构和临床医生小组新建立的合作。