EFFECT OF BLOOD TRANSFUSIONS AFTER TRANSPLANT SURGERY

移植手术后输血的影响

• 批准号: 3230437
• 负责人: JUAN C SCORNIK
• 金额: $ 10.45万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230437
• 关键词: antibody formation; antileukocyte isoantibody; blood transfusion; cryopreservation; human subject; human therapy evaluation; immunosuppression

This proposal is a continuation of our research on the mechanisms of broad sensitization, particularly regarding the effects of blood transfusions after transplant rejection. Our previous results are the subject of 11 papers, 8 published and 3 in press. We now propose to study the rate of HLA antibody synthesis in broadly sensitized patients and its inhibition by different immunosuppressive agents. Our objectives are to develop effective protocols to inhibit anti-HLA antibody synthesis, to minimize the risk of toxicity of such protocols, and to identify the patients who may benefit the most, so that transplantation could be considered as a viable option despite the presence of broadly reactive antibodies. The study contemplates perturbing the system by means of a plasma exchange, which will induce, first, an artificial drop of antibody concentration, and second, a rebound to its original levels. This rebound can be used as an indication of the rate of antibody synthesis in a given patient and it will be measured by rigorously quantitative techniques. Subsequent plasma exchanges performed under different conditions of immunosuppression will allow to determine the effectiveness of the drug protocols using the patient as its own control- If the patients need to be transfused during the study period, cryopreserved, HLA matched blood will be given to minimize the immunogenicity of blood transfusions. With this design we will find out, after a 4-6 week period, whether the antibody levels in a specific patient are refractory or sensitive to the immunosuppression utilized, and the factors that are associated with, and could be predictive of, one or the other outcome. In contrast to previous trials, the patients will be considered for transplantation only if the antibody synthesis is clearly suppressed. In this revised application, preliminary results on 3 patients evaluated after plasma exchanges and immunosuppression are presented. The results demonstrate the feasibility of the studies proposed. They also suggest the possibility of successful use of plasma exchanges without immunosuppression, a fact that, if confirmed, could lead to a wide utilization of this procedure.

该提案是我们对该机制研究的延续 广泛的敏感性，特别是关于血液的影响 移植排斥反应后的输血。 我们之前的结果是 该主题发表了 11 篇论文，其中 8 篇已发表，3 篇已出版。 我们现在 提议广泛研究 HLA 抗体合成率 致敏患者及其不同的抑制作用 免疫抑制剂。 我们的目标是开发有效的 抑制抗 HLA 抗体合成的方案，以尽量减少 此类方案的毒性风险，并识别患者 谁可能受益最大，以便移植能够 尽管存在广泛的 反应性抗体。 该研究考虑扰乱系统 通过血浆交换，这将首先诱导 人为降低抗体浓度，二是反弹 恢复到原来的水平。 这个反弹可以作为一个指标 特定患者的抗体合成率 通过严格的定量技术进行测量。 随后的 不同条件下进行血浆置换 免疫抑制将有助于确定免疫抑制的有效性 使用患者作为自身对照的药物方案 - 如果 患者在研究期间需要输血， 将给予冷冻保存的 HLA 匹配血液，以尽量减少 输血的免疫原性。 通过这个设计，我们将 4-6周后查明抗体水平是否 特定患者对该药物难治或敏感 使用的免疫抑制以及相关因素 并可以预测一个或另一个结果。 在 与之前的试验相比，患者将被考虑 仅在抗体合成明确的情况下进行移植 压制。 在此修订后的申请中，3 名患者的初步结果 血浆置换和免疫抑制后进行评估 提出。 结果证明了研究的可行性 建议的。 他们还建议成功使用 没有免疫抑制的血浆交换，事实是，如果 证实，可能会导致该程序的广泛利用。