BIOCHEMISTRY, PHYSIOLOGY AND IMMUNOLOGY OF PLATELETS

血小板的生物化学、生理学和免疫学

• 批准号: 2214728
• 负责人: SIMON KARPATKIN
• 金额: $ 22.93万
• 依托单位: NEW YORK UNIVERSITY
• 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 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2214728
• 关键词: B lymphocyte; CD5 molecule; HIV envelope protein gp120; HIV infections; affinity chromatography; antiantibody; antibody receptor; antiidiotype antibody; antiviral antibody; autoantigens; autoradiography; blood chemistry; clone cells; complement; complement receptor; cross immunity; ethylene glycols; fibronectins; human immunodeficiency virus 1; human subject; immune complex; immunoglobulin G; immunoglobulin M; immunoglobulin structure; immunoprecipitation; integrins; leukocyte adhesion molecules; monocyte; platelets; thrombocytopenic purpura

This grant focuses on the role of idiotype-anti-idiotype complexes (both internal image and non-internal image) in the peripheral destruction of platelets in HIV-1-related immunologic thrombocytopenic purpura (HIV-1-ITP). HIV-1-ITP patients have markedly elevated levels of PEG-precipitable immune complexes in their sera and on their platelets. These are macromolecular complexes containing IgG, IgM, C3, and anti-HIV-1gp120 idiotype-anti-idiotype complexes (Ab1-Ab2). Ab2 correlates with thrombocytopenia, r=0.9, P is less than 0.001. Internal image idiotype-anti-idiotype complexes bind 10 fold greater to platelets, than non-internal image complexes. HIV-1-ITP patients also have markedly elevated levels of %CD5+ B cells, implicated in autoimmunity by the production of a low affinity multispecific predominantly IgM antibody against self, other antigens and the Fc portion of IgG. These Ab's have been implicated in the production of a primordial idiotype-anti-idiotype network. %CD5+ B cells correlated with thrombocytopenia, r=0.5, p is less than 0.01. We propose to: I. Study the mechanism of binding of PEG-precipitable immune complexes to platelets (internal image vs non-internal image). It is not via the platelet Fc receptor. Is it via a C3b/C3bi receptor?. II. Study the mechanism of binding of affinity-purified Ab1-Ab2 complexes + complement to platelets. III. Investigate the possible presence of other idiotype-anti-idiotype IgG complexes as well as IgM-IgG complexes or HIV-1 virus-Ab complexes. IV. Determine whether CD5+ B cells of HIV-1-ITP patients secrete anti-idiotype and/or anti-Fc antibodies against HIV-1 patient's IgG as well as antibodies against platelets. V. Study the effect of PEG-precipitable complexes and laboratory-assembled affinity-purified complexes on the adhesive and phagocytic interaction of platelets with monocytes. Study the role of the LeuCAM integrins in platelet-monocyte adhesion and phagocytosis by employing specific anti-functional MoAb's. These studies could help understand the basic immunologic pathophysiology of HIV-1 infection as well as devise clinical strategies for the treatment and/or eradication of HIV-1 -ITP.

该基金主要关注独特型-抗独特型复合物的作用（ 内部图像和非内部图像）的外围破坏 HIV-1相关性免疫性血小板减少性紫癜患者血小板的变化 （HIV-1-ITP）。 HIV-1-ITP患者中， 在他们的血清和血小板上的PEG可沉淀免疫复合物。 这些是含有IgG、IgM、C3和C4的大分子复合物。 抗HIV-1gp 120独特型-抗独特型复合物（Ab 1-Ab 2）。 AB2 与血小板减少相关，r=0.9，P <0.001。内部 成像独特型-抗独特型复合物与血小板的结合是其10倍， 比非内在的意象复合体更复杂。 HIV-1-ITP患者也有明显的 % CD 5 + B细胞水平升高，与 低亲和力多特异性主要IgM抗体的生产 针对自身、其它抗原和IgG的Fc部分。 这些抗体有 与原始独特型-抗独特型的产生有关 网络% CD 5 + B细胞与血小板减少相关，r=0.5，p较小 比0.01。我们建议：研究了结合机理， PEG-可沉淀的血小板免疫复合物（内部图像与 非内部图像）。 它不是通过血小板Fc受体。是通过一个 C3 b/C3 bi受体？二. 研究了结合机理， 亲和纯化的Ab 1-Ab 2复合物+血小板补体。三. 研究是否存在其他独特型-抗独特型IgG 复合物以及IgM-IgG复合物或HIV-1病毒-Ab复合物。 四. HIV-1-ITP患者CD 5 + B细胞是否分泌 抗HIV-1患者IgG的抗独特型和/或抗Fc抗体， 以及抗血小板的抗体。 五.研究 PEG-可沉淀复合物和实验室组装的亲和纯化的 复合物对血小板粘附和吞噬作用的影响 单核细胞 LeuCAM整合素在血小板-单核细胞中作用的研究 粘附和吞噬作用。 这些研究有助于了解基本的免疫病理生理学 HIV-1感染，并制定临床策略， 治疗和/或根除HIV-1 -ITP。