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SLE井井有条，是一种复发和复发疾病。但是，复发的病理生理学知之甚少。项目4旨在为有关SLE复发的病理生理学的以下关键问题提供严格的答案：1）什么原因导致SLE复发？人们普遍认为，某些事件，例如心理压力，感染，雌激素或暴露于Ultraviolent（UV）辐射会触发SLE复发：1）是什么导致SLE复发？人们普遍认为，某些事件，例如心理压力，感染，雌激素或暴露于紫外线（UV）辐射会触发SLE复发。但是，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，为什么有些复发肾复发）？ 我们假设复发的严重程度取决于触发的强度和/或某些SLE复发的“加速器”的存在。但是，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，为什么有些复发肾复发）？我们假设复发的严重程度取决于触发的强度和/或某些SLE复发的“加速器”的存在。加速器可能包括获得的因素，例如趋化因子或白三烯的高表达。加速器也可能是遗传因素，例如功能失调的CR1，异常高剂量的CR基因或具有增强炎症作用的突变趋化因子。 3）可以准确预测SLE复发吗？开发一个实用的统计模型来早期预测严重的SLE复发将是SLE管理的巨大进步。项目4的设计很简单。遗传和免疫学上的SLE疾病患者（n = 100、50例，肾脏受累和从未肾脏受累的50名从未有肾脏受累的患者）将由项目1、2和3的遗传和免疫学表征，并将经过精心遵循定期的假定触发器和SLE复发加速器的措施。预计在项目4的5年后进行了300多个复发。使用逻辑回归，我们将确定SLE复发，其严重性和预测的真实风险因素。项目4在测试的广度，深度和范围上是前所未有的，以鉴定人类SLE肾炎的遗传和临床危险因素。项目4将有助于满足我们对人SLE及其肾炎的理解。