INDUCTION OF ANTIIDIOTYPIC ANTIBODIES BY PRE TRANSPLANT

通过移植前诱导抗独特型抗体

基本信息

批准号：
3071150
负责人：
STANLEY C JORDAN
金额：
$ 5.49万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-07-01 至 1986-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3071150
关键词：
antiantibody antibody formation antiidiotype antibody antileukocyte isoantibody blood transfusion child (0-11) electrofocusing homologous transplantation human subject immune complex immunochemistry immunoelectrophoresis immunofluorescence technique kidney transplantation preoperative state tissue donors

项目摘要

During the past decades, renal allograft transplantation has emerged as the desired treatment of children with end stage renal disease (ESRD). Despite increasingly sophisticated methods of HLA-typing and efforts to transplant well matched kidneys, allograft rejection continues to be the major cause of allograft failure and treatment of rejection a cause of patients morbidity. This would imply that factors other than HLA antigens may play a role in the determination of allograft rejection. One of the major factors that improves allograft survival is pre-transplant blood transfusions (BT). The exact mechanism(s) responsible for this enhancing effect remain unknown. It has been suggested that (BT) induce enhancement or an active immunologic unresponsiveness to donor antigens. Two (BT) protocols are now operational at UCLA. In PROTOCOL I, potential cadaver transplant recipients will be randomized to either a group receiving 20 small-dose transfusions (2.5 cc/kg) over 5 months or a group receiving 5 full transfusions (10 cc/kg) over the same time period. In PR0TOCOL II, ESRD patients with greater than 70 percent HLA antibodies will be transfused from known donors to determine if the high titer HLA antibodies can be reduced. Preliminary data generated in our laboratory shows that post-BT patients generate blocking factors which inhibit anti-HLA antibodies specific for donor/recipient discrepant HLA antigens. Within the framework of the outlined protocols, we plan to evaluate post-BT serum samples for the presence of blocking factors (antiidiotypic antibody) using techniques developed in our laboratory. Briefly, post-BT sera will be evaluated every two weeks for circulating immune complexes (CICs), and lymphocytotoxic antibody (LCA). Patients will be categorized according to immune responses; (i.e., CIC(+)/LCA(+), CIC(+)/LCA(-), etc.). Analysis of sera (both IC(+)/IC(-)), for anti-F(ab')2 and anti-IgG antibodies and for specific antiidiotypic antibodies, (i.e. anti-anti-HLA) will be done. Immunoelectrophoretic analysis of sera will be carried out to confirm the antibody nature of demonstrated blocking factors. Another group of non-HLA antigens (endothelial antigens, E-antigens) are important mediators of certain types of allograft rejection. BTs inhibit E-antibody formation. We will investigate the possibility that post-BT inhibition of E-antibody formation is related to antiidiotypic antibody formation (i.e. anti-anti-E-antibody). It is anticipated that these investigations will provide data on the mechanism(s) responsible for the known allograft enhancing effect of BTs. This information will allow us to isolate specific allograft-enhancing factors and develop new approaches to the prevention and treatment of allograft rejection.

在过去的几十年里，同种异体肾移植已成为终末期肾病（ESRD）儿童的理想治疗。尽管 HLA 分型方法和移植工作日益复杂肾脏匹配良好，同种异体移植排斥仍然是主要原因同种异体移植失败的原因和排斥反应的治疗发病率。这意味着 HLA 抗原以外的因素也可能发挥作用在确定同种异体移植排斥反应中发挥作用。主要之一提高同种异体移植存活率的因素是移植前血液输血（BT）。负责这种增强的确切机制效果仍未知。有人建议（BT）诱导增强或对供体抗原的主动免疫无反应。两个（BT）协议现已在加州大学洛杉矶分校运行。在议定书一中，潜在的尸体移植受者将被随机分配到接受 20 5 个月内小剂量输血（2.5 cc/kg）或接受 5 同一时间段内充分输血（10 cc/kg）。在协议 II 中， HLA 抗体超过 70% 的 ESRD 患者将被从已知捐献者处进行输血以确定是否存在高效价 HLA 抗体可以减少。我们实验室生成的初步数据表明 BT 后患者会产生抑制抗 HLA 的阻断因子针对供体/受体差异 HLA 抗原的特异性抗体。之内根据概述的方案框架，我们计划评估 BT 后血清使用样本检测阻断因子（抗独特型抗体）的存在我们实验室开发的技术。简而言之，BT 后血清将是每两周评估一次循环免疫复合物 (CIC)，以及淋巴细胞毒性抗体（LCA）。患者将根据以下情况进行分类免疫反应；（即 CIC(+)/LCA(+)、CIC(+)/LCA(-) 等）。分析血清（IC(+)/IC(-)），用于抗 F(ab')2 和抗 IgG 抗体以及将进行特异性抗独特型抗体（即抗抗HLA）。将进行血清免疫电泳分析以确认抗体性质已证实的阻断因素。另一组非HLA 抗原（内皮抗原、E抗原）是重要的介质某些类型的同种异体移植排斥。 BT 抑制 E-抗体形成。我们将研究 E 抗体的 BT 抑制作用的可能性形成与抗独特型抗体的形成有关（即抗抗E抗体）。预计这些调查将提供已知同种异体移植机制的数据 BT 的增强效果。这些信息将使我们能够隔离特定的同种异体移植增强因子并开发新的方法预防和治疗同种异体移植排斥反应。