Predicting Systemic Autoimmunity through Follow-up of Blood Relatives

通过血亲随访预测系统性自身免疫

• 批准号: 7942912
• 负责人: JUDITH A JAMES
• 金额: $ 49.97万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7942912
• 关键词: Address; Affect; African American; Age-Years; American; Area; Autoantibodies; Autoimmune Diseases; Autoimmunity; Biological Markers; Blood; Clinical; Clinical Data; Clinical Treatment; Collaborations; Collection; Connective Tissue Diseases; Consent; DNA; Department of Defense; Development; Diagnosis; Disease; Employee; Environmental Exposure; Environmental Risk Factor; European; Evaluation; Event; FDA approved; Family member; Family-Based Registry; Female; First Degree Relative; Follow-Up Studies; Funding; Future; Generations; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; Genetic screening method; Grant; Hydroxychloroquine; Immune response; Individual; Interferon-alpha; Intervention; Investigation; Literature; Lupus; Medical; Medical Records; Mission; Multiple Sclerosis; Onset of illness; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pilot Projects; Plague; Plasma; Population; Populations at Risk; Pre-Post Tests; Prevention; Prevention strategy; Preventive; Questionnaires; RNA; Relative (related person); Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Scleroderma; Screening procedure; Serological; Serum; Specificity; Specimen; Supplementation; Symptoms; Systemic Lupus Erythematosus; Testing; Therapeutic; Time; Undifferentiated; Vitamin D; Vitamin D Deficiency; Woman; Work; base; cohort; cytokine; disorder risk; follow-up; genetic risk factor; health disparity; high risk; information gathering; pathogen; patient population; pre-clinical; prevent; public health relevance; repository; response; systemic autoimmune disease

DESCRIPTION (provided by applicant): The Challenge Area addressed by this project is Area 9: Health Disparities Research. The specific topic for this application is "Prevention Strategies that Target Disproportionately Affected Lupus and Scleroderma Patient Populations". Systemic lupus erythematosus is a prototypic systemic autoimmune disease for which no new FDA treatment has been approved in over 50 years. Identification of "high risk" groups for SLE development would allow intervention with preventive therapies. Systemic lupus has a known genetic predisposition and family members are carry an increased risk of developing clinical disease. Over the past 15 years, our consortium of investigators has assembled a collection of nearly 6,000 unaffected blood relatives of SLE patients who had serum samples collected and stored on average 7.6 years ago. These individuals were clinically well at that time, but many have potentially transitioned to clinical lupus in the interim. Re-contacting these individuals (who have provided consent for re-contact for future studies) will provide us with a unique opportunity to rapidly assemble a group of SLE patients with specimens before and at/after clinical disease onset. In addition, cohorts of individuals with some increased genetic risk, and likely autoantibodies, who do not transition to clinical disease will be compiled. Select serological biomarkers, including select autoantibody profiles and serum alpha interferon activity, will be tested for association with transition to clinical lupus. Additional lupus- associated environmental factors, such as markers of vitamin D deficiency and abnormal humoral immune responses to common pathogens, will be tested as predictors of SLE disease onset. Evaluation of genetic risk polymorphisms with increased risk of SLE can be further studied. Finally, a large collection of clinical, demographic, and therapeutic information, in combination with biospecimens from historical collections and follow-up studies, will be available for future investigation. This project will help to identify "high risk" individuals for SLE development, defining outstanding populations for potential preventative therapies directed toward these or future biomarkers. Autoimmune diseases are estimated to afflict as many as 50,000,000 Americans. PUBLIC HEALTH RELEVANCE: This application tests genetic and serologic biomarkers of autoimmunity, cytokine activity, and abnormal environmental responses as predictors of autoimmune disease onset. ARRA funds would allow rapid generation of a SLE transition cohort by follow-up of historical, at-risk individuals to establish disease predictors to aid in prevention strategies. Biospecimens and associated clinical data will be biobanked to test future alternate hypotheses.

描述（由申请人提供）：该项目所解决的挑战领域是领域9：健康差异研究。本申请的特定主题是“针对受不对称影响的狼疮和硬皮病患者人群的预防策略”。系统性红斑狼疮是一种典型的系统性自身免疫性疾病，50多年来没有新的FDA治疗方法被批准。确定SLE发展的“高风险”群体将允许进行预防性治疗干预。系统性狼疮具有已知的遗传易感性，并且家庭成员具有发生临床疾病的增加的风险。在过去的15年里，我们的研究者联盟收集了近6,000名SLE患者的未受影响的血亲，他们的血清样本平均在7.6年前收集和储存。这些人当时临床表现良好，但许多人在此期间可能过渡到临床狼疮。重新联系这些个体（他们已同意为未来研究重新联系）将为我们提供一个独特的机会，快速收集一组SLE患者的临床疾病发作前后的标本。此外，还将编制遗传风险增加的个体队列，以及可能的自身抗体，这些个体不会转变为临床疾病。将检测选定的血清学生物标志物，包括选定的自身抗体谱和血清α干扰素活性，以确定其与临床狼疮转变的相关性。其他狼疮相关的环境因素，如维生素D缺乏的标志物和对常见病原体的异常体液免疫反应，将作为SLE疾病发作的预测因子进行测试。遗传风险多态性与SLE风险增加的评估可以进一步研究。最后，大量的临床、人口统计学和治疗信息，以及来自历史收集和随访研究的生物标本，将可用于未来的研究。该项目将有助于识别SLE发展的“高风险”个体，定义针对这些或未来生物标志物的潜在预防性治疗的杰出人群。据估计，自身免疫性疾病折磨着多达50，000，000的美国人。 公共卫生相关性：本申请测试了自身免疫、细胞因子活性和异常环境反应的遗传和血清学生物标志物作为自身免疫性疾病发作的预测因子。ARRA基金将允许通过对历史高危个体进行随访来快速生成SLE过渡队列，以建立疾病预测因子，从而帮助制定预防策略。将对生物样本和相关临床数据进行生物样本库，以检验未来的替代假设。