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Autoimmunity Center of Excellence (ACE) at Stanford

斯坦福大学自身免疫卓越中心 (ACE)

基本信息

批准号：
8461899
负责人：
CHARLES GARRISON FATHMAN
金额：
$ 62.26万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8461899
关键词：
Academic Medical Centers Address Adult Adult-Onset Still&apos s Disease Affect Age of Onset Animals Antibodies Antigens Area Autoantibodies Autoimmune Diseases Autoimmune Process Autoimmunity Basic Science Biological Assay Biological Markers Biopsy Blinded Blood Blood Cells Blood Circulation Blood Vessels Blood specimen Bronchoalveolar Lavage Fluid CD28 gene CD3 Antigens CD4 Positive T Lymphocytes CSF3 gene Cell Lineage Cell surface Cells Cellular biology Characteristics Child Childhood Chronic Childhood Arthritis Clinical Clinical Immunology Clinical Investigator Clinical Research Clinical Trials Collaborations Complex Cutaneous Data Defect Degenerative polyarthritis Dermatologic Dermatology Dermis Development Diffuse Scleroderma Discipline Disease Disease-Modifying Second-Line Drugs Double-Blind Method Education Educational Materials Educational process of instructing Effector Cell Elements Endothelial Cells Enrollment Eragrostis Ethnic group Face Faculty Fibrosis Flare Freezing Frequencies Funding Gastroesophageal reflux disease Gene Expression Goals Granulocyte-Macrophage Colony-Stimulating Factor Hand Helper-Inducer T-Lymphocyte Human IL17 gene IL2RA gene Immune Immunohistochemistry Immunologic Monitoring Immunotherapeutic agent In Vitro Infiltration Inflammation Infusion procedures Instruction Interferon Type II Interferons Interleukin 2 Receptor Interleukin-1 Interleukin-17 Interleukin-2 Interleukin-4 Interleukin-6 Interleukin-8 Investigation Joints Knowledge Laboratories Laboratory Research Lead Leadership Legal patent Lesion Lymphocyte Maintenance Mediating Medical Methotrexate Microscopic Modeling Monoclonal Antibodies Mononuclear Mus Organ Outcome Papillary Pathogenesis Pathologic Pathway interactions Patients Peptides Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phase Physical therapy Physiological Pilot Projects Placebos Plasma Play Population Prevalence Process Production Productivity Proteins Psoriasis Psoriatic Arthritis Publishing Pulmonology RNA Reagent Regulation Regulatory T-Lymphocyte Reporting Research Research Personnel Research Project Grants Research Proposals Resources Rheumatoid Arthritis Rheumatology Role Safety Sampling Schedule Scientist Scleroderma Serum Signal Transduction Site Skin Skin Manifestations Staining method Stains Survival Rate Symptoms Synovial Fluid Synovial Membrane Systemic Lupus Erythematosus Systemic Scleroderma T memory cell T-Cell Activation T-Cell Proliferation T-Lymphocyte TNF gene Technology Testing Therapeutic Therapeutic Intervention Tissues Translating Translational Research Translations Treatment Efficacy United States Universities Urine Validation Vasodilator Agents Visit Woman Work active method antimicrobial peptide arthropathies base body system comparative efficacy control trial cytokine efalizumab efficacy testing high school immunoregulation improved insight interest keratinocyte loss of function macrophage medical schools memory CD4 T lymphocyte men new technology novel novel strategies novel therapeutics peripheral blood pre-clinical prevent programs research study response skin disorder success systemic autoimmune disease technology development therapeutic target therapy development trafficking treatment duration treatment strategy urinary

项目摘要

DESCRIPTION (provided by applicant): The Stanford ACE will support an integrated basic and clinical research program focused on tolerance induction and immune modulation to prevent or treat autoimmune disease. The major theme of the Stanford Autoimmunity Center of Excellence (the Center) is the study of the regulation of CD4 T cells in pathogenesis and treatment of autoimmune diseases. The Center will support and be supported by other ACE groups across the United States; and will take advantage of Stanford's documented leadership in basic and clinical research, technology development, and education in clinical immunology. Success of the Center will be supported by the interrelationships previously established at Stanford among clinician scientists from multiple departments studying autoimmune diseases in multiple organs and tissues. The Stanford ACE will be composed of outstanding basic and clinical investigators from multiple disciplines at Stanford Medical School and proposes both a basic Research Project, centered on CD4 T cell unresponsiveness, and a translational Research Project to study a new T cell lineage (termed Th17 cells) that is characterized by the ability of these lymphocytes to secrete high levels of the proinflammatory cytokine interleukin-17 (IL-17). Proposed clinical research projects encompass three different autoimmune diseases [diffuse systemic sclerosis (SSc), psoriatic arthritis and systemic juvenile idiopathic arthritis (SJIA)] that afflict adults and children, as well as organ systems including joints, skin, blood elements, and blood vessels, and will both test efficacy of therapy and develop tests to characterize the mechanisms of action of these therapeutics. The proposed Pilot and Feasibility Project proposes a two year research plan in Systemic Juvenile Idiopathic Arthritis (SJIA) patients to identify and validate urine peptide biomarkers that predict (a) response to TNF inhibition; (b) response to IL-1 inhibition; and (c) impending disease flare. In addition, this proposal will provide other ACE groups access to cutting edge reagents and technology platforms for studying human autoimmune diseases, and dissemination of Educational Materials that can be used by other ACEs to teach clinical immunology concepts to high school, undergraduate, graduate, postgraduate, and clinical fellows and faculty. The Stanford ACE proposes to support integrated basic, pre-clinical and clinical research by proposing and then conducting basic and translational research into the mechanism of CD4 T cell unresponsiveness; two clinical trials that include novel therapies and mechanistic studies of these therapies for autoimmune diseases; and a pilot proposal that intends to develop new bi omarkers of disease. PROJECT 1A: Clinical Component (Genovese, M) CLINICAL COMPONENT DESCRIPTION (provided by applicant): Stanford University Medical Center (SUMC) has an extraordinary tradition of medical, translational, and basic science research. An outstanding array of resources, faculty, and facilities will be available to support the proposed ACE site at Stanford University. This proposal brings together a skilled group of translational researchers with a track record of productivity in both laboratory and clinical research focusing on human autoimmune mediated diseases. Stanford has brought together various disciplines to demonstrate both accomplishment and ability to work together with the following fields represented: Adult Rheumatology, Dermatology, Pulmonary Medicine, and Pediatric Rheumatology. The projects chosen for this submission highlight the significant collaborations that exist between Rheumatology (Adult and Pediatric), Dermatology and Pulmonary Medicine. Both clinical trials projects explore dermatologic and rheumatologic manifestations of diseases such as Psoriatic arthritis and Systemic Sclerosis. Clinical Trial Concept 1: The use of an anti- IL-17 mab in the treatment of active Psoriatic Arthritis Primary Hypothesis: The proportion of patients achieving the ACR 20 response from Baseline to Week 14 among active Psoriatic Arthritis (PSA) subjects treated with IL-17 mab is larger than the proportion achieving ACR 20 response from Baseline to Week 14 among active PSA subjects treated with placebo Objectives: The goal of this study is to determine the safety and efficacy of a monoclonal antibody to lnterleukin-17 (IL-17 mab) in the treatment of PsA with active skin and joint disease. Clinical Trial Concept 2: The use of CTLA-4lg (abatacept) in subjects with diffuse systemic sclerosis Primary hypothesis: Given several lines of evidence supporting the role of activated T cells in affected skin, we hypothesize that inhibiting T cell activation may lead to significant clinical improvement in skin manifestations in patients with diffuse systemic sclerosis (dSSc), and that changes in tissue and blood autoantibody and cytokine profiles will be associated with clinical response. Objectives: The primary goal of this study is to determine the safety and efficacy of CTLA-4lg (Abatacept) for the treatment of cutaneous manifestations of dSSc RELEVANCE (See instructions): The Stanford ACE will support an integrated basic and clinical research program focused on tolerance induction and immune modulation to prevent or treat autoimmune (Al) disease. The Stanford ACE proposes clinical research projects that encompass three different autoimmune diseases (SSc, psoriatic arthritis and SJIA), and proposes to study the MoA of therapeutics for preventing or treating different Al diseases.

描述（由申请人提供）：斯坦福ACE将支持一个综合的基础和临床研究项目，重点研究耐受性诱导和免疫调节，以预防或治疗自身免疫性疾病。斯坦福自身免疫卓越中心（中心）的主要主题是研究CD4 T细胞在自身免疫性疾病发病机制和治疗中的调节作用。该中心将支持并得到美国其他ACE组织的支持；并将利用斯坦福大学在基础和临床研究、技术开发和临床免疫学教育方面的领先地位。该中心的成功将得到斯坦福大学多个部门的临床科学家之间建立的相互关系的支持，这些科学家研究多种器官和组织的自身免疫性疾病。斯坦福ACE将由来自斯坦福医学院多个学科的优秀基础和临床研究人员组成，并提出一个以CD4 T细胞无反应性为中心的基础研究项目，以及一个研究新的T细胞谱系（称为Th17细胞）的转化研究项目，其特点是这些淋巴细胞能够分泌高水平的促炎细胞因子白细胞介素-17 （IL-17）。拟议的临床研究项目包括三种不同的自身免疫性疾病[弥漫性系统性硬化症（SSc）、银屑病关节炎和系统性青少年特发性关节炎（SJIA）]，这些疾病折磨着成人和儿童，以及包括关节、皮肤、血液元素和血管在内的器官系统，并将测试治疗的疗效，并开发测试来表征这些治疗的作用机制。拟议的试点和可行性项目提出了一项为期两年的系统性幼年特发性关节炎（SJIA）患者的研究计划，以确定和验证预测(a)对TNF抑制反应的尿肽生物标志物；(b)对IL-1抑制的反应；(c)即将爆发的疾病。此外，该提案将为其他ACE小组提供研究人类自身免疫性疾病的尖端试剂和技术平台，并传播可供其他ACE使用的教育材料，以向高中，本科生，研究生，研究生和临床研究员和教师教授临床免疫学概念。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Measurement of mast cell surface molecules by high-throughput immunophenotyping using transcription (HIT).

通过转录高通量免疫表型 (HIT) 测量肥大细胞表面分子。

DOI：
10.1007/978-1-4939-1568-2_24
发表时间：
2015
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Haddon,DJames;Jarrell,JustinA;Hughes,MichaelR;Snyder,Kimberly;McNagny,KellyM;Kattah,MichaelG;Utz,PaulJ
通讯作者：
Utz,PaulJ

Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus.