RETROVIRUS-INDUCED IMMUNE PLATELET ABNORMALITIES

导致血小板减少症的免疫性血小板破坏发生在 大量感染人类免疫缺陷的患者 1型病毒（HIV）。 抗体与血小板相互作用的机制 导致血小板清除增加的原因仍然不清楚， 过去六年的调查。 一个一致的发现是， 从这些研究中发现， 大多数HIV感染者血小板相关免疫球蛋白 患者，包括许多血小板计数正常且无 血小板减少症 该项目旨在实现两个 主要目的：1）阐明HIV相关的免疫调节机制， 免疫性血小板破坏（HIV-ITP），以及2）确定 HIV感染者血小板免疫球蛋白水平升高的相关性 状态 本提案的具体目标将检验以下假设： HIV-ITP的机制不是由于血小板负荷增加， 免疫球蛋白（或免疫复合物），但最有可能是由于 自身抗体 此外，具体目标将考验第二个 假设血小板免疫球蛋白水平升高是继发性的， HIV对巨核细胞或血小板的直接影响， 与循环免疫球蛋白或免疫复合物平衡。 作为 作为拟议研究的一部分，两组艾滋病毒血清阳性患者， 一个有ITP的证据，另一个血小板计数正常， 定期招募和跟踪。 一系列体外 血小板和血清学研究将与 血小板存活率研究，以确定血小板如何与 体液免疫系统在艾滋病毒感染状态，当 关系导致血小板破坏。 感染恒河猴 猴免疫缺陷病毒与艾滋病病毒的临床相似性 感染的人类，包括血小板减少症的相似发生率。 对SIV感染猴的拟议工作包括血小板存活研究 在血小板减少动物和体外血小板研究中， 减少性和减少性动物。 这项工作将是 逆转录病毒诱导的猿猴模型开发的重要一步 血小板异常

Immunopathic platelet destruction leading to thrombocytopenia occurs in a significant number of patients infected with human immunodeficiency virus type 1 (HIV). The mechanism of antibody platelet interaction leading to increased platelet removal remains obscure despite much investigation over the past six years. One consistent finding that has emerged from these studies is the presence of increased amounts of immunoglobulins associated with platelets from most HIV infected patients, including many with normal platelet counts and no history of thrombocytopenia. This project has been designed to accomplish two major goals: 1) to elucidate the mechanism of HIV-associated immunopathic platelet destruction (HIV-ITP), and 2) to determine the relevance of elevated platelet immunoglobulin levels in the HIV infected state. The specific aims of this proposal will test the hypothesis that the mechanism of HIV-ITP is not due to the increased platelet load of immunoglobulins (or immune complexes), but is most likely due to autoantibody. In addition, the specific aims will test the second hypothesis, that increased platelet immunoglobulin levels are secondary to a direct HIV effect on megakaryocytes or platelets and do not reflect equilibration with circulating immunoglobulins or immune complexes. As part of the proposed study, two cohorts of HIV seropositive patients, one with evidence of ITP and the other with normal platelet counts will be recruited and followed at regular intervals. A series of in vitro platelet and serologic studies will be performed in conjunction with platelet survival studies to determine how platelets relate to the humoral immune system in the HIV infected state and when that relationship leads to platelet destruction. Rhesus monkeys infected with simian immunodeficiency virus display clinical similarity to HIV infected humans, including a similar incidence of thrombocytopenia. Proposed work on SIV infected monkeys includes platelet survival studies on thrombocytopenic animals and in vitro platelet studies on both non- thrombocytopenic and thrombocytopenic animals. This work will be a major step in the development of a simian model for retroviral induced platelet abnormalities.