MECHANISMS OF ENDOTHELIAL CELL INJURY IN TTP/HUS

血栓性血小板减少性紫癜(TTP)是一种多系统疾病 特点是微小的血管病理性溶血性贫血，血小板减少， 神经系统异常，少见的发烧和肾脏异常。 当与成人急性肾功能衰竭有关时，术语“溶血” 尿毒症综合征“(HUS)经常被使用。TTP/HUS是一种知之甚少的 这种疾病尽管最近在治疗上取得了重大进展，但仍然有 与之相关的重大发病率和死亡率。一批 已提出机制来解释这种疾病的发病机制。 过程，但尽管为此付出了大量努力， 大部分发病机制尚不清楚，病因尚不清楚。 这项提议将试图探索患者的疾病机制。 使用TTP/HUS。基本的前提是 各种形式的TTP/HUS是内皮细胞的扰动 血小板和凝血酶的二次激活，导致微血管 血栓形成。具体目标是： 1.研究原发性和继发性TTP/HUS患者是否存在 免疫球蛋白和非免疫球蛋白因子影响血小板和 血管内皮细胞及其作用机制的研究 影响微血管血栓形成的因素。 2.建立评估内皮细胞损伤和/或损伤的体外模型 对目标1中确定的免疫球蛋白活性作出反应的激活。 3.确定临床病程、实验室检查结果、对 经典TTP的治疗和临床结果，并与HIV- 关联的TTP。 这项研究的长期目标是提高对 TTP/HUS的部分或全部发病机制。在 过程中，这项研究将试图确定在 HIV相关TTP的发病机制与更典型的TTP/HUS。

Thrombotic thrombocytopenic purpura (TTP) is a multi-system disorder characterized by micro angiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, and less commonly, fever and renal abnormalities. When associated with acute renal failure in adults, the term "hemolytic uremic syndrome" (HUS) is often used. TTP/HUS is a poorly understood disease that despite recent major therapeutic advances, still has significant morbidity and mortality associated with it. A number of mechanisms have been proposed to explain the pathogenesis of this disease process, but despite a great deal of effort devoted to this, the pathogenesis for the most part remains unclear and the etiology unknown. This proposal will attempt to explore mechanisms of disease in patients with TTP/HUS. The basic premise is that the unifying feature of the various forms of TTP/HUS is perturbation of the endothelial cell with secondary activation of platelets and thrombin, leading to microvascular thrombosis. The specific aims are: 1. To study patients with primary and secondary TTP/HUS for the presence of immunoglobulin and non-immunoglobulin factors that affect platelets and endothelial cells and characterize the mechanisms of action of these factors in mediating microvascular thrombosis. 2. To develop an in vitro model to assess endothelial cell injury and/or activation in response to immunoglobulin activity identified in aim 1. 3. To define the clinical course, laboratory findings, response to therapy, and clinical outcome of classical TTP and compare it with HIV- associated TTP. The long-term goal of this research is to improve the understanding of the pathogenesis of TTP/HUS in some or all of its various forms. In the process, the study will attempt to determine if there are differences in the pathogenesis of HIV-associated TTP vs. more typical TTP/HUS.