Midcareer Investigator Award in Patient-Oriented Resear

描述（由申请人提供）：系统性红斑狼疮（SLE）是 一种主要影响年轻人的全身性炎症性自身免疫性疾病， 少数民族，绝经前妇女。高达75%的SLE患者会经历一些 在其病程期间的神经系统表现类型（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，虽然全范围 NS的参与还没有得到很好的表征。两大领域 候选人的研究一直是1）临床和血清学研究 NPSLE发展的预测因子，和2）免疫介导的血栓形成 抗磷脂抗体（antiphospholipid antibody，aPL）这一建议的主旨是 将扩大一个强大的临床研究计划，在一个队列中研究NPSLE 主要是墨西哥裔美国SLE患者，通过1）确定频率 在这个明确的队列中， 和2）通过以下方法评估微栓塞信号（MES）的频率和 经颅多普勒超声（TCD）及MES与脑血管病变的关系 2组SLE患者（UTHSCSA和 Dusseldorf，德国），有和没有aPL。SLE患者的风险增加 血栓性事件，包括心肌梗死和中风。几 NPSLE的表现可能有脑缺血作为共同的基础 病理生理机制，如认知功能障碍和中风。潜在 SLE缺血的原因包括血管痉挛、微血管疾病、血栓形成 伴有或不伴有动脉粥样硬化，很少伴有血管炎。的频率 动脉粥样硬化在SLE中的重要性，动脉粥样硬化在SLE相关卒中中的重要性 风险，或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，炎症，免疫， SLE特有的治疗相关因素都可能参与其中。与 在中期职业调查员奖的支持下，候选人将与 一个多学科小组，由各领域的资深调查员和研究员组成， 血管和脑成像，免疫遗传学，流行病学，精神病学 和神经心理学这项合作将提供非常重要的 关于亚临床血管疾病的患病率和程度的信息 SLE的相关危险因素。我们将会学到很多关于 遗传因素和自身抗体对血管疾病风险的重要性 SLE可能适用于其他风险增加的人群， 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.