CLINICAL AND SEROLOGIC PREDICTORS OF NEUROPSYCHIATRIC SLE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：这项前瞻性队列研究的长期目标是：(1)描述系统性红斑狼疮(SLE)患者神经系统(NS)受累的谱，系统性红斑狼疮(SLE)是导致高达75%的患者发病率的重要原因；(2)确定可能是特定靶向NS表现(包括中风、认知功能障碍和精神症状)特有的重要危险因素。初步证据表明，在以墨西哥裔美国人(MA)为主的SLE人群中，中风和其他NS表现的频率很高。在这个多年项目中将检验的具体假设是：(1)抗磷脂(APL)和抗载脂蛋白H(anti-apoH)抗体水平持续异常的SLE患者发生首次血栓闭塞事件的风险更高；(2)SLE患者认知功能障碍的发展将暂时与APL和抗apoH抗体水平异常有关；(3)SLE患者精神症状(精神病、抑郁或焦虑)的发展将与血清抗核糖体P(anti-P)水平异常暂时相关；(4)SLE疾病活动性、SLE相关器官损害的累积性或心血管危险因素的存在都会以一种独立于APL、抗apoH或抗P抗体状态的方式增加发生靶向NS表现的风险。 研究计划：我们将招募来自大圣安东尼奥地区的SLE患者参加这项研究。将每四个月进行一次神经学、认知学、精神病学、风湿学和免疫学的系列评估，并在为期五年的终点事件时进行评估。 方法：构建Kaplan-Meier曲线，比较抗体阳性组和抗体阴性组血栓事件发生的时间。考克斯回归将被用来构建多变量模型，以控制潜在混杂因素的影响。认知功能障碍将作为一个连续变量进行衡量，与抗体水平相比，每个患者的功能波动约为基线。将密切关注多重比较问题。一种类似于认知功能障碍的方法将用于精神表现。 临床意义：据估计，高达75%的系统性红斑狼疮(SLE)患者在病程的某个时候会出现某种类型的神经系统表现。该项目将确定可能导致重大发病率的风险因素，并提供目前无法获得的与系统性红斑狼疮相关的NS症状的关键自然历史数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The long-term objectives of this prospective cohort study are to: (1) characterize the spectrum of nervous system (NS) involvement in patients with Systemic Lupus Erythematosus (SLE), a significant cause of morbidity in up to 75% of patients and (2) define important risk factors which may be unique for specifically targeted NS manifestations including stroke, cognitive dysfunction, and the psychiatric manifestations. Preliminary evidence suggests that frequency of stroke and other NS manifestations in our predominantly Mexican-American (MA) SLE population is high. The specific hypotheses which will be tested in this multi-year project are: (1) The risk of initial thrombo-occlusive events will be higher in SLE patients who have persistently abnormal levels of antiphospholipid (aPL) and anti-apolipoprotein H (anti-apoH) antibodies; (2) The development of cognitive dysfunction in SLE patients will be temporarily associated with abnormal levels of aPL and anti-apoH antibodies; (3) The development of psychiatric manifestations (psychosis, depression or anxiety) in SLE patients will be temporally associated with abnormal serum levels of anti-ribosomal P (anti-P); and (4) SLE disease activity, cumulative SLE-related organ damage or the presence of cardiovascular risk factors will all contribute to the risk of developing targeted NS manifestations in a way that is independent of aPL, anti-apoH or anti-P antibody status. RESEARCH PLAN: We will recruit SLE patients from the greater San Antonio area for enrollment into the study. Serial neurological, cognitive, psychiatric, rheumatological and immunological evaluations will be performed every four months and at the time of an end-point event for five years. METHODS: Kaplan-Meier Curves will be constructed comparing the time between thrombotic events in antibody positive and negative groups. Cox regression will be used to construct multivariate models to control for the effects of the potential confounders. Cognitive dysfunction will be measured as a continuous variable, with the fluctuations in functioning about the baseline for each patient compared with antibody levels. Close attention will be paid to the problems of multiple comparisons. An approach similar to that described for cognitive dysfunction will be used for psychiatric manifestations. CLINICAL RELEVANCE: It has been estimated that up to 75% of patients with Systemic Lupus Erythematosus (SLE) experience some type of nervous system manifestations at some point in their disease course. This project will identify risk factors which may account for significant morbidity and provide crucial natural history data about SLE-related NS manifestations which are currently unavailable.