IMMUNOGENICITY OF HLA-MATCHED BLOOD TRANSFUSIONS

HLA 匹配输血的免疫原性

• 批准号: 3345159
• 负责人: JUAN C SCORNIK
• 金额: $ 10.42万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345159
• 关键词: antileukocyte isoantibody; biological polymorphism; blood donor; blood group antigens; blood transfusion; bone marrow transplantation; cryopreservation; flow cytometry; histocompatibility typing; human subject; hybridomas; immunohematology; kidney transplantation; lymphocyte; major histocompatibility complex; monoclonal antibody; platelet preservation; platelet transfusion; plateletpheresis; platelets; serology /serodiagnosis

HLA-matched donors are being used with increasing frequency for transfusion of platelets or other blood products, for bone marrow transplants and for kidney transplants. However, the exquisite polymorphism of the HLA system makes it difficult, and sometimes impossible, to find perfectly matched donors for a particular patient. Since some HLA types are crossreactive, that is, 2 or more antigens share common determinants, that property is being used to select additional donors who mismatch selectively for crossreactive antigens. While it is hoped that a patient having a given HLA antigen will not make antibodies to a crossreactive one, there is some evidence that, in fact, occurs. The objective of this proposal is to build, experimentally, the data base that will allow to select donors based on poor HLA immunogenicity. This research will utilize the analytical capabilities of flow cytometry as a technique to detect and quantitate antibodies to lymphocytes and platelets with a high degree of sensitivity. The experimental design contemplates testing sera from broadly sensitized patients against cells from donors who are HLA identical or mismatched for crossreactive antigens, studying as many combinations as donors are available for that patient. The HLA-matched donors will be selected from our 5,000 HLA-typed donor file using the same algorithms utilized to find HLA-matched platelet donors. In addition, the in vivo immunogenicity of HLA-matched platelet transfusions will be studied by monitoring the humoral response elicited to the lymphocytes and platelets of the matched donor. Analysis of Blood Bank data in the pertinent patient population indicates that the number of patients available for these in vivo studies will be sufficient for statistically valid conclusions. We expect these results will clarify the impact of the HLA polymorphism in HLA sensitization create more rational basis to overcome its untoward effects.

HLA 匹配的捐献者越来越频繁地用于输血 血小板或其他血液制品，用于骨髓移植和 肾脏移植。 然而，HLA系统精致的多态性 使得找到完美匹配变得困难，有时甚至是不可能 特定患者的捐赠者。 由于某些 HLA 类型具有交叉反应性， 也就是说，2个或多个抗原具有共同的决定簇，该特性是 用于选择与选择性不匹配的其他捐赠者 交叉反应抗原。 虽然希望患者具有给定的 HLA 抗原不会产生交叉反应性抗体，有一些 确实发生的证据。 该提案的目的是 实验性地建立数据库，以便根据情况选择捐助者 HLA 免疫原性较差。 本研究将利用分析 流式细胞术作为检测和定量技术的能力 对淋巴细胞和血小板具有高度敏感性的抗体。 实验设计考虑测试广泛致敏的血清 患者对抗来自与 HLA 相同或不匹配的捐献者的细胞 交叉反应抗原，研究与供体一样多的组合 可供该患者使用。 HLA 匹配的捐献者将从 我们的 5,000 个 HLA 型供体文件使用与查找相同的算法 HLA 匹配的血小板捐献者。 此外，其体内免疫原性 HLA 匹配的血小板输注将通过监测体液 对匹配供体的淋巴细胞和血小板引起反应。 对相关患者群体血库数据的分析表明 可用于这些体内研究的患者数量将是 足以得出统计上有效的结论。 我们期待这些结果 将阐明 HLA 多态性对 HLA 致敏的影响 更理性的基础来克服其不良影响。