CLINICAL AND SEROLOGIC PREDICTORS OF NEUROPSYCHIATRIC SLE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目的：这项前瞻性队列研究的长期目标是：(1)表征系统性红斑狼疮（SLE）患者的神经系统（NS）受累谱，这是高达75%患者发病率的重要原因；(2)确定可能是特异性靶向NS表现的重要危险因素，包括中风、认知功能障碍和精神表现。初步证据表明，在以墨西哥裔美国人（MA）为主的SLE人群中，卒中和其他NS表现的频率很高。在这个多年的项目中将测试的具体假设是：(1)抗磷脂（aPL）和抗载脂蛋白H（抗apoh）抗体水平持续异常的SLE患者发生初始血栓闭塞事件的风险更高；(2) SLE患者认知功能障碍的发展与aPL和抗apoh抗体水平异常暂时相关；(3) SLE患者的精神表现（精神病、抑郁或焦虑）的发展与血清中抗核糖体P （anti-P）水平异常具有暂时性的相关性；(4) SLE疾病活动性、SLE相关器官的累积损伤或心血管危险因素的存在都将以独立于aPL、抗apoh或抗p抗体状态的方式增加发生靶向性NS表现的风险。研究计划：我们将从大圣安东尼奥地区招募SLE患者入组研究。将每4个月进行一次神经、认知、精神病学、风湿病学和免疫学系列评估，并在5年内的终点事件发生时进行评估。方法：构建Kaplan-Meier曲线，比较抗体阳性组和阴性组血栓形成时间。Cox回归将用于构建多变量模型，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测量，与抗体水平相比，每个患者的基线功能波动。我们将密切关注多重比较的问题。与治疗认知功能障碍类似的方法将用于治疗精神疾病。临床相关性：据估计，高达75%的系统性红斑狼疮（SLE）患者在其病程的某个阶段经历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sles相关的NS表现的重要自然历史数据。

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.