IMMUNOLOGY OF HUMAN PLATELETS (HIV-1-ITP)

人类血小板的免疫学 (HIV-1-ITP)

• 批准号: 2471487
• 负责人: SIMON KARPATKIN
• 金额: $ 26.87万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2471487
• 关键词: B lymphocyte; CD5 molecule; HIV infections; antibody receptor; apoptosis; clinical research; crosslink; disease /disorder etiology; enzyme linked immunosorbent assay; flow cytometry; genetic library; human subject; humoral immunity; immunoglobulin genes; integrins; laboratory mouse; laboratory rabbit; lymphopoiesis; megakaryocytes; monoclonal antibody; platelets; protein sequence; thrombocytopenia; tissue /cell culture; western blottings

DESCRIPTION: Studies are proposed exploring the mechanisms of increased platelet destruction and decreased platelet production focusing on anti-GPIIIa antibodies directed at what appears to be an immunodominant determinant, GPIIIa 49-66, in the serum of HIV-ITP patients. Previous work has revealed that amounts of antibodies isolated from immune complexes of HIV-ITP patients are inversely related to platelet count levels, and induce thrombocytopenia in mice which can be reversed by infusion of GPIIIa 49-66 conjugated with albumin. Therefore, it is hypothesized that antibodies to this particular region of GPIIIa might have particular significance in the pathogenesis of HIV related immune thrombocytopenia. The applicants seek to determine whether anti-49-66 antibodies are polyclonal or oligoclonal; whether they might be the result of molecular mimicry of antigens of infectious origin; and whether or not there is a unique idiotype repertoire for anti-49-66. They will also explore whether elevated CD5+ B cells, which are primitive B cells described in HIV-ITP patients, might be responsible for anti-49-66 as well as for anti-idiotype antibodies. Finally, they will analyze the mechanism(s) by which anti-GPIIIa inhibits MK development via apoptosis determining whether the specificity of these antibodies is to 49-66; which stage of MK maturation is inhibited; the mechanism of apoptosis; and whether anti-GPIIIa impairs megakaryocytopoiesis in vivo.

描述：提出了研究，以探讨增加的机制 血小板破坏和血小板产生减少 抗GPIIIA抗体，针对似乎是免疫主导的抗体 hiv-ITP患者的血清中，决定因素，GPIIIA 49-66。 以前的工作 已经揭示了从免疫复合物中分离出的抗体量 HIV-ITP患者与血小板计数水平成反比，并诱导 小鼠的血小板减少症可以通过输注GPIIIA 49-66的逆转 与白蛋白结合。 因此，假设抗体 GPIIIA的这个特定区域可能在 HIV相关免疫血小板减少症的发病机理。 申请人寻求 确定抗49-66抗体是多克隆还是寡克隆； 它们是否可能是分子模仿抗原的结果 传染病；以及是否有独特的白痴型曲目 用于反49-66。 他们还将探索是否升高CD5+ B细胞 是HIV-ITP患者中描述的原始B细胞，可能是负责的 用于抗49-66以及抗IDiotype抗体。 最后，他们会的 分析抗GPIIIA抑制MK发育的机制 凋亡确定这些抗体的特异性是否是 49-66;抑制MK成熟的哪个阶段；机制 凋亡；以及抗GPIIIA是否会在体内损害巨核细胞菌。