Hemorrhagic Diseases

出血性疾病

• 批准号: 7076995
• 负责人: Richard Herbert Aster
• 金额: $ 47.69万
• 依托单位: VERSITI WISCONSIN, INC.
• 依托单位国家: 美国
• 财政年份: 1970
• 资助国家: 美国
• 起止时间: 1970-06-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076995
• 关键词: animal tissue; antigen antibody reaction; blood disorder diagnosis; blood group antigens; clinical research; diagnosis design /evaluation; drug interactions; hemorrhagic disorders; heparin; human subject; immunohematology; immunoprecipitation; interleukin 8; isoantibody; isoantigen; leukopenia; platelet factor 4; platelet transfusion; platelets; polymerase chain reaction; thrombocytopenia; thrombosis; western blottings

DESCRIPTION (provided by applicant): Target molecules recognized by platelet-reactive antibodies. The role played by rare platelet-specific antigens as triggers for neonatal alloimmune thrombocytopenia (NATP) will be characterized by studying mother/father pairs of unresolved NATP cases. Recombinant target proteins will be developed to facilitate NATP diagnosis. The biology of a newly identified genetic trait (high-expression of blood group A and B antigens on platelets) and its significance in platelet transfusion and neonatal thrombocytopenia will be examined. The 5b (HNA-3a) neutrophil/platelet alloantigen, a cause of fatal transfusion reactions in patients transfused with anti-5b, will be characterized. Drug-induced immune cytopenia (DIIC) induced by drugs other than heparin. Mechanisms by which drugs induce drug-dependent antibodies, promote binding of these antibodies to their targets and cause blood cell destruction will be examined at a molecular level. The importance of drug metabolites as triggers for these antibodies will be defined. The possibility that drug-dependent antibodies specific for markers on endothelial cells influence the clinical course of DIIC will be explored. Improved methods for diagnosis of DIIC will be developed. Heparin-induced thrombocytopenia/ thrombosis (HIT). Studies will be undertaken in a large cohort of patients suspected of having HIT to resolve the question of whether antibodies specific for IL-8, a CXC chemokine homologous to PF4, have a role in pathogenesis. Pathogenesis of other immune-mediated platelet disorders. Patients with other immune-mediated platelet disorders relevant to the objectives of this grant will be studies as time and resources permit.

描述（由申请人提供）：由血小板反应性抗体识别的靶分子。稀有血小板特异性抗原作为新生儿同种免疫性血小板减少症（NATP）的触发作用的特征是研究未解决的NATP病例的母亲/父亲对。将开发重组靶蛋白以促进NATP诊断。将检查新鉴定的遗传特征（血小板上的高表达A和B抗原）的生物学及其在血小板输血和新生儿血小板减少症中的重要性。将表征5B（HNA-3A）中性粒细胞/血小板同具有抗原，这是抗5B输血的患者致命输血反应的原因。 药物诱导的肝素以外的药物诱导的免疫细胞质（DIIC）。药物诱导药物依赖性抗体，促进这些抗体与其靶标的结合并引起血细胞破坏的机制将在分子水平上检查。将定义药物代谢物作为这些抗体的触发因素的重要性。探索对内皮细胞上标记的药物依赖性抗体影响DIIC的临床过程的可能性。将开发改进的DIIC诊断方法。 肝素诱导的血小板减少症/血栓形成（HIT）。将在涉嫌打击的大量患者中进行研究，以解决针对PF4同源的CXC趋化因子特异性的抗体是否在发病机理中起作用。 其他免疫介导的血小板疾病的发病机理。与该赠款目标有关的其他免疫介导的血小板疾病的患者将在时间和资源许可证中进行研究。