CLINICAL AND SEROLOGIC PREDICTORS OF NEUROPSYCHIATRIC SLE

神经精神系统性红斑狼疮的临床和血清学预测因素

• 批准号: 7718713
• 负责人: ROBIN L BREY
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718713
• 关键词: Accounting; Antibodies; Anxiety; Area; Attention; Clinical; Cognitive; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Disease regression; End Point; Enrollment; Evaluation; Event; Frequencies; Funding; Grant; Impaired cognition; Institution; Lupus Erythematosus; Measures; Mental Depression; Mexican Americans; Modeling; Morbidity - disease rate; Natural History; Nervous system structure; Neurologic; Neuropsychiatric Systemic Lupus Erythematosus; Organ; Patients; Population; Psychotic Disorders; Recruitment Activity; Research; Research Personnel; Resources; Risk; Risk Factors; Serological; Serum; Source; Stroke; Systemic Lupus Erythematosus; Testing; Time; United States National Institutes of Health; beta 2-glycoprotein I; cardiovascular risk factor; clinically relevant; experience; prospective

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它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) 描述系统性红斑狼疮 (SLE) 患者的神经系统 (NS) 受累范围，这是高达 75% 患者发病的重要原因；(2) 确定重要的危险因素，这些因素可能是针对特定 NS 表现（包括中风、认知功能障碍和精神表现）所特有的。 初步证据表明，在我们以墨西哥裔美国人 (MA) 为主的 SLE 人群中，中风和其他 NS 表现的频率很高。 这个多年项目将检验的具体假设是：（1）抗磷脂（aPL）和抗载脂蛋白H（抗apoH）抗体水平持续异常的SLE患者中，初始血栓闭塞事件的风险较高； (2) SLE患者认知功能障碍的发生会暂时与aPL和抗apoH抗体水平异常相关； (3) SLE患者精神表现（精神病、抑郁或焦虑）的发生将暂时与抗核糖体P（抗P）血清水平异常相关； (4) SLE 疾病活动性、累积的 SLE 相关器官损伤或心血管危险因素的存在都会以独立于 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：我们将从大圣安东尼奥地区招募 SLE 患者参加该研究。 每四个月以及五年内发生终点事件时将进行一系列神经学、认知、精神病学、风湿学和免疫学评估。 方法：构建 Kaplan-Meier 曲线，比较抗体阳性组和阴性组中血栓事件之间的时间。 Cox 回归将用于构建多元模型以控制潜在混杂因素的影响。 认知功能障碍将作为连续变量进行测量，与抗体水平相比，每个患者的功能在基线附近波动。 将密切关注多重比较的问题。 与针对认知功能障碍所描述的方法类似的方法将用于精神症状的治疗。 临床相关性：据估计，高达 75% 的系统性红斑狼疮 (SLE) 患者在病程的某个时刻会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有关 SLE 相关 NS 表现的重要自然史数据。