Midcareer Investigator Award in Patient-Oriented Resear

描述(申请人提供)：系统性红斑狼疮(SLE) 一种全身性炎症性自身免疫性疾病，主要影响年轻人， 少数，绝经前的女性。高达75%的SLE患者经历了一些 病程中神经系统表现的类型(称为 神经精神性狼疮或NPSLE)。最常见的表现包括 认知功能障碍、精神疾病和中风，尽管 对NS的参与还没有得到很好的描述。的两个主要领域 候选人的研究一直是临床和血清学的研究 NPSLE发展的预测因素，以及2)免疫介导的血栓形成 与抗磷脂抗体(APL)有关。这项建议的主旨是 将在队列中扩大研究NPSLE的强大临床研究计划 主要是墨西哥裔美国人的SLE患者通过1)确定频率 在这一明确的队列中加速动脉粥样硬化的风险因素 和2)评估微栓子信号(MES)的频率和 经颅多普勒(TCD)及其与脑血管的关系 两组SLE患者的缺血和认知功能障碍(UTHSCSA和UTHSCSA 德国杜塞尔多夫)，无论有没有APL。系统性红斑狼疮患者的风险增加 适用于血栓事件，包括心肌梗塞和中风。几个 NPSLE的临床表现可能以脑缺血为共同基础 病理生理机制，如认知功能障碍和中风。潜力 系统性红斑狼疮的缺血原因包括血管痉挛、微血管疾病、血栓形成 有或没有动脉粥样硬化，很少有脉管炎。的频率 系统性红斑狼疮的动脉粥样硬化，动脉粥样硬化在系统性红斑狼疮相关卒中的重要性 风险，或者是否有重要的遗传或种族影响是未知的。 传统的血管危险因素，炎性、免疫性和 系统性红斑狼疮特有的治疗相关因素都可能参与其中。使用 在职业生涯中期调查员奖的支持下，候选人将与 由该地区资深调查人员和研究员组成的多学科团队 中风、血管和脑成像、免疫遗传学、流行病学、精神病学 和神经心理学。这一合作努力将提供非常重要的 关于亚临床血管疾病的患病率和程度的信息 以及与SLE相关的危险因素。我们将了解更多关于这位亲戚的信息 遗传因素和自身抗体在血管疾病风险中的重要性 SLE可能适用于其他人群，也有更高的风险 脑缺血和血管性痴呆。

DESCRIPTION (provided by the applicant): Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease that affects predominantly young, minority, pre-menopausal women. Up to 75% of patients with SLE experience some type of nervous system manifestations during their disease course (termed neuropsychiatric lupus or NPSLE). The most common manifestations include cognitive dysfunction, psychiatric disease and stroke, although the full range of NS involvement has not been well characterized. Two major areas of the candidate's research have been the study of 1) clinical and serologic predictors for the development of NPSLE, and 2) immune-mediated thrombosis related to antiphospholipid antibodies (aPL). The major thrust of this proposal will be to expand a strong clinical research program studying NPSLE in a cohort of predominantly Mexican-American SLE patients by 1) determining the frequency of and risk factors for accelerated atherosclerosis in this well-defined cohort and 2) evaluating the frequency and of microembolic signals (MES) by transcranial doppler (TCD) and the relationship between MES and cerebrovascular ischemia and cognitive dysfunction in 2 cohorts of SLE patients (UTHSCSA and Dusseldorf, Germany) with and without aPL. SLE patients are at increased risk for thrombotic events, including both myocardial infarction and stroke. Several NPSLE manifestations may have cerebral ischemia as a common underlying pathophysiologic mechanism, e.g. cognitive dysfunction and stroke. Potential causes of ischemia in SLE include vasospasm, microvascular disease, thrombosis with or without atherosclerosis, and rarely, vasculitis. The frequency of atherosclerosis in SLE, the importance of atherosclerosis in SLE-related stroke risk, or whether there are important genetic or racial influences are unknown. Traditional vascular risk factors, inflammatory, immunological, and treatment-related factors specific to SLE are all likely to be involved. With the support of the Mid-Career Investigator Award, the candidate will work with a multidisciplinary team of established investigators and fellows in the areas of stroke, vascular and brain imaging, immunogenetics, epidemiology, psychiatry and neuropsychology. This collaborative effort will provide very important information regarding prevalence and extent of sub-clinical vascular disease and associated risk factors in SLE. Much will be learned about the relative importance of genetic factors and autoantibodies on vascular disease risk in SLE that is likely to apply to other populations also at increased risk for cerebral ischemia and vascular dementia.