BIOCHEMISTRY, PHYSIOLOGY AND IMMUNOLOGY OF PLATELETS

血小板的生物化学、生理学和免疫学

• 批准号: 3334622
• 负责人: SIMON KARPATKIN
• 金额: $ 20.69万
• 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/3334622
• 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; 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.

这项赠款重点是愚蠢的anti-idiotype型复合物的作用（均 内部图像和非内部图像） 与HIV-1相关的免疫血小板减少紫菜中的血小板 （HIV-1-ITP）。 HIV-1-ITP患者的水平显着升高 PEG peccectipable可在其血清和血小板中呈现出来的免疫复合物。 这些是包含IgG，IgM，C3和的大分子复合物 抗HIV-1GP120白痴-Anti-Idiotype型复合体（AB1-AB2）。 AB2 与血小板减少症相关，r = 0.9，p小于0.001。内部的 图像白痴型 - 抗iDiotypy型复合物结合10倍与血小板更大， 比非内部图像复合物。 HIV-1-ITP患者也明显 ％CD5+ B细胞的水平升高，与自身免疫有关 低亲和力多特异性的产生IgM抗体 反对自我，其他抗原和IgG的FC部分。 这些腹部有 与生产原型型 - anti-Idiotype有关 网络。 ％CD5+ B细胞与血小板减少症相关，r = 0.5，P较少 大于0.01。我们提出：I。研究结合机制 PEG peg-precipable免疫复合物至血小板（内部图像与 非内部图像）。 它不是通过血小板FC受体。是通过 C3B/C3BI受体？。 ii。 研究结合机制 亲和纯化的AB1-AB2复合物 +与血小板补充。 iii。 研究其他白痴 - 抗iDiotypy igG的可能存在 复合物以及IgM-IgG复合物或HIV-1病毒-AB复合物。 iv。 确定HIV-1-ITP患者的CD5+ B细胞是否分泌 针对HIV-1患者IgG的抗IDITYPE型和/或抗FC抗体AS 以及针对血小板的抗体。 V.研究 PEG-PRECIPITIBLE络合物和实验室组装亲和力纯化 血小板与粘附和吞噬相互作用的复合物与 单核细胞。 研究leucam整联蛋白在血小板单细胞中的作用 通过采用特定的抗功能性摩押，粘附和吞噬作用。 这些研究可以帮助理解基本的免疫病理生理学 HIV-1感染以及制定临床策略 HIV -1 -ITP的治疗和/或消除。