Pathogenesis of SLE relapse in humans

人类 SLE 复发的发病机制

• 批准号: 6570868
• 负责人: LEE A. HEBERT
• 金额: $ 29.59万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570868
• 关键词: chemokine; disease /disorder etiology; disease /disorder proneness /risk; genetic susceptibility; hematology; human subject; infection; leukotrienes; longitudinal human study; mathematical model; model design /development; nephritis; pathologic process; patient oriented research; personal log /diary; psychometrics; relapse /recurrence; sex hormones; statistics /biometry; stress; systemic lupus erythematosus; ultraviolet radiation; urinalysis

Human SLE is well organized as a disease of relapses and remissions. However, the pathophysiology of relapse is poorly understood. Project 4 is designed to provide rigorous answers to the following key questions regarding the pathophysiology of SLE relapse: 1) What cause SLE relapse? It is widely believed that certain events such as psychological stress, infection, estrogens, or exposure to ultraviolent (UV) radiation can trigger SLE relapse: 1) What causes SLE relapse? It is widely believed that certain events such as psychological stress, infection, estrogens, or exposure to ultraviolet (UV) radiation can trigger SLE relapse. However, the evidence is largely anecdotal. 2) What determines severity of SLE relapse (e.g., why are some relapses renal relapses)? We hypothesize that the severity of relapse is determined by the strength of the trigger and/or the presence of certain "accelerators" of SLE relapse. However, the evidence is largely anecdotal. 2) What determines severity of SLE relapse (e.g., why are some relapses renal relapses)? We hypothesize that the severity of relapse is determined by the strength of the trigger and/or the presence of certain "accelerators" of SLE relapse. Accelerators could include acquired factors such as high expression of chemokines or leukotrienes. Accelerators could also be genetic factors such as dysfunctional CR1, an abnormally high dose of CR genes, or a mutated chemokine that has enhanced inflammatory effects. 3) Can SLE relapse be accurately predicted? Developing a practical statistical model for the early prediction of severe SLE relapse would be a great advance in the management of SLE. The design of Project 4 is straightforward. SLE patients with relapsing disease (N=100, 50 with renal involvement and 50 who never had renal involvement) will be characterized genetically and immunologically by Projects 1, 2, and 3, and will be meticulously followed with regular measures of the putative triggers and accelerators of SLE relapse. More than 300 relapses are expected during the 5 years of follow-up in Project 4. Using logistic regressions we will identify the authentic risk factor for SLE relapse, its severity, and its prediction. Project 4 is unprecedented in breadth, depth, and scope of testing to identify genetic and clinical risk factors for human SLE nephritis. Project 4 will help fulfill a major unmet need in our understanding of human SLE and its nephritis.

人类系统性红斑狼疮被认为是一种复发和缓解的疾病。然而，复发的病理生理学还知之甚少。项目4旨在为以下关于SLE复发的关键问题提供严格的答案：1)SLE复发的原因是什么？人们普遍认为，某些事件，如心理压力、感染、雌激素或暴露在紫外线(UV)辐射下可引发SLE复发：1)是什么导致SLE复发？人们普遍认为，某些事件，如心理压力、感染、雌激素或暴露在紫外线(UV)辐射下，会引发系统性红斑狼疮复发。然而，证据在很大程度上是轶事。2)是什么决定了SLE复发的严重程度(例如，为什么有些复发是肾脏复发)？我们假设复发的严重程度取决于触发因素的强度和/或SLE复发的某些“加速器”的存在。然而，证据在很大程度上是轶事。2)是什么决定了SLE复发的严重程度(例如，为什么有些复发是肾脏复发)？我们假设复发的严重程度取决于触发因素的强度和/或SLE复发的某些“加速器”的存在。促进剂可能包括获得性因素，如高表达趋化因子或白三烯。加速器也可能是遗传因素，如功能失调的CR1，异常高剂量的CR基因，或具有增强炎症效应的突变趋化因子。3)系统性红斑狼疮复发能否准确预测？开发一种实用的统计模型来早期预测严重的SLE复发将是SLE治疗的一大进步。项目4的设计很简单。有复发疾病的SLE患者(N=100，50名肾脏受累，50名从未肾脏受累)将通过项目1、2和3进行遗传学和免疫学特征描述，并将定期对SLE复发的可能触发因素和加速因素进行跟踪。在项目4的5年随访中，预计有超过300例复发。使用Logistic回归分析，我们将确定SLE复发的真实危险因素、其严重性和预测。项目4在广度、深度和范围上都是史无前例的，以确定人类SLE肾炎的遗传和临床风险因素。项目4将帮助满足我们对人类系统性红斑狼疮及其肾炎的一个主要的未得到满足的需求。