A Systems Biology Approach for Pediatric and Adult Autoimmune Diseases

儿童和成人自身免疫性疾病的系统生物学方法

• 批准号: 8470118
• 负责人: Maria Virginia Pascual
• 金额: $ 62.99万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8470118
• 关键词: Academic Medical Centers; Address; Adolescent; Adult; Adult Dermatomyositis; Antigens; Appointment; Area; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Automobile Driving; B-Lymphocytes; Basic Science; Biological; Biological Assay; Biological Markers; Biology; Blinded; Blood; Blood typing procedure; CD4 Positive T Lymphocytes; Caring; Cell Maturation; Cells; Cellular biology; Child; Childhood; Chronic small plaque psoriasis; Clinical; Clinical Investigator; Clinical Research; Clinical Sciences; Clinical Trials; Clinical Trials Design; Collaborations; Commit; Communicable Diseases; Complex; Controlled Clinical Trials; Data; Databases; Dendritic Cell Vaccine; Dendritic Cells; Dermatology; Dermatomyositis; Development; Diabetes Mellitus; Diagnostic tests; Discipline; Disease; Double-Blind Method; Early treatment; Environment; Gene Expression Profiling; Genes; Genomics; Goals; Harvest; Helper-Inducer T-Lymphocyte; Hospitals; Human; Immune response; Immunologist; Immunology; In Vitro; Individual; Institutes; Interferons; Interleukin-1; Interleukin-12; Interleukin-17; Islets of Langerhans; Islets of Langerhans Transplantation; Laboratories; Laboratory Research; Learning; Lupus; Malignant Neoplasms; Measures; Medical center; Methods; Multiple Sclerosis; Pathogenesis; Pathway interactions; Patients; Pediatric Neurology; Phase; Physicians; Pilot Projects; Placebos; Process; Property; Protocols documentation; Psoriasis; Psoriatic Arthritis; Randomized; Research; Research Infrastructure; Research Personnel; Resources; Rheumatology; Role; Safety; Sampling; Sampling Studies; Scientist; System; Systemic Lupus Erythematosus; Systems Biology; T cell response; T-Lymphocyte; T-Lymphocyte Subsets; Techniques; Testing; Texas; Time; Transplantation; Tumor Immunity; Universities; Vaccines; anakinra; analytical tool; assay development; base; bench to bedside; biological systems; congenital immunodeficiency; cytokine; design; experience; flexibility; improved; innovation; interest; melanoma; multidisciplinary; new therapeutic target; novel; novel diagnostics; overexpression; programs; response; type I and type II diabetes

DESCRIPTION (provided by applicant): We propose to create an Autoimmunity Center of Excellence that will incorporate the efforts of clinicians, human immunologists (both basic and translational), physician-scientists with clinical expertise and research experience in autoimmunity, bioinformaticians, and geriomics/systems biologists. Together, the assembled group has an extensive background in clinical trials and a proven track record for merging basic and clinical science. This team is committed to bringing innovative treatments from the laboratory bench to their patients' bedside. Within this collaborative setting, a systems biology approach is proposed to focus on both pediatric and adult autoimmune diseases. The goals of the Center are: 1) To assess the efficacy of novel targeted therapies, 2) To develop simple and robust biomarkers using state-of-the-art genomic approaches, 3) To understand the role of recently identified T cell subsets in disease pathogenesis, and 4) To assess antigen-specific responses in pediatric and adult autoimmune diseases. These projects will provide a better understanding of the pathogenesis of specific autoimmune diseases and allow us to develop a strategy to assess disease activity based on novel transcriptional markers as well as to identify autoantigen-specific immune responses. The Center will deliver: 1) Innovative clinical trials targeting specific cytokines in psoriasis & dermatomyositis. 2) Development of biomarkers for dermatomyositis, psoriasis, lupus and multiple sclerosis. 3) Identification of novel therapeutic targets in dermatomyositis. 4) Development of assays to test autoantigen-specific immune responses. 5) Development of a unique microarray database of human autoimmune diseases. CLINICAL COMPONENT (Cush, J) CLINICAL COMPONENT DESCRIPTION (provided by applicant): Baylor Institute for Immunology Research aims to bring together a distinguished team of clinical investigators to conduct cutting-edge clinical trials on specific autoimmune diseases. This unique group of investigators and clinicians has appointments at Baylor University Medical Center, UT Southwestern Medical Center, Texas Scottish Rite Hospital in Dallas and Northwestern University. These talented individuals have been enlisted from diverse programs with subspecialties in dermatology, rheumatology, neurology, pediatrics, and human immunology. They provide a set of inimitable resources for clinical trials and have a proven track record for merging basic and clinical science. Indeed, this team is committed to bringing innovative treatments from the laboratory bench to their patients' bedside. With such outstanding collaborative players, a systems biology approach is proposed here which investigates both pediatric and adult autoimmune disease. To this end, two Phase II randomized, double-blind, placebo-phase controlled clinical trials are proposed. The first trial investigates whether blocking IL-1 with Anakinra will result in objective disease improvement for patients with Juvenile Dermatomysitis. The trial design will demonstrate: 1) if the time to improvement for patients receiving Anakinra early in the study will be earlier than those who receive later treatment; and 2) if the proportion of patients improved at week 8 of the blinded phase will be significantly greater in the early treatment group. Mechanistic studies will utilize gene expression profiling assays to find a novel diagnostic test for JDM as well as disease activity measures and biomarkers to follow and predict patients' response to therapy. The second clinical project proposes to use a-IL-17 in patients with plaque psoriasis as well as psoriatic arthritis. Specifically, this study will assess the safety and efficacy of a-IL-17 in these patients and determine both the time to achieve endpoints of a PASI 75 or ACR20 and sustainability of such responses at 24 weeks. Associated studies will establish blood transcriptional markers to predict clinical responses in patients treated with a-IL-17, determine if transcriptional scores can be used to assess disease activity, and analyze the effect(s) of IL-17 blockade on B and T cell subsets. A dynamic team of clinical investigators assembled at BUR to conduct state-of-the-art clinical trials on autoimmune disease would be of great value and accelerate the process of bringing research from the laboratory bench to the bedside. This team proposes two important trials that will assess a-IL-1 treatment in Juvenile Dermatomyositis and IL-17 blockade in psoriatic diseases.

描述（由申请人提供）：我们建议建立一个卓越的自身免疫中心，该中心将整合临床医生、人类免疫学家（基础和转化）、具有临床专业知识和自身免疫研究经验的内科科学家、生物信息学家和老年组学/系统生物学家的努力。总的来说，该团队在临床试验方面拥有广泛的背景，并在合并基础科学和临床科学方面有着良好的记录。该团队致力于将创新的治疗方法从实验室工作台带到患者的床边。在这种协作设置，系统生物学的方法被建议集中在儿童和成人自身免疫性疾病。