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Research of the regulation pf acute allograft rejection in ABO-blood type incompatible kidney transplantation

ABO血型不合肾移植急性排斥反应调控研究

基本信息

批准号：
11470333
负责人：
TAKAHASHI Kota
金额：
$ 8.83万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470333/
关键词：
ABO-incompatible kidney transplantation Humoral rejection Standarization of anti-A B antibody titre estimation Elimination of antibodies Immunosuppressive therapy Splenectomy Pathological criteria Anti-endothelial cell antibody 抗体価測定標準化

项目摘要

ABO-blood type incompatible kidney transplantation is one of a big challenge to overcome the immunological barrier of humoral rejection caused by acquired natural antibodies. In this study we have achieved "the state of the art" today and published the books entitled "ABO incompatible kidney transplantation". In the article, head investigator Takahashi described about the history, patient and graft survival data update in Japan, antigenic molecules and antibodies, indication and peri-dperacive evaluation and management, immunosuppression, extra-corporeal immuno-modulation, standard operative methods of transplantation and splenectomy, infection control, clinico-pathological research and case reports, and future perspectives. In the article, we also present a new strategy of pathological croteria for allograft rejection in ABO-incompatible kidney transplantation.In addition, in order to evaluate pre-sensitization status and high risk group for acute rejection in kidney transplantation, we have developed cellular ELISA system to detect anti glomerular endothehal cell antibodies(AECA-GEC) and anti-human umbilical vein endothelial cells(AECA-HUVEG) in kidney transplant recipient serum.In the sequential serum examination in 22 recipients, AECA-GEC positive group showed significantly high frequency, of acute rejection.episodes This phenomena suggests that AECA-GEC positive status may indicate pre-sensitization status against organ-specific antigens expressed on renal glomerular endothelial cells which might cause the disturbance of microcirculation of the graft leading to acute humoral and cellular rejection.We also provide a possibility of an new strategy of immunosuppressive therapy including elimination of acquired antibodies and continuous immunosuppression of antibody production by lymphocytes in highly sensitized recipients.

ABO血型不合的肾移植是克服获得性天然抗体引起的体液排斥反应这一免疫屏障的一大挑战。在这项研究中，我们已经达到了今天的“最先进水平”，并出版了题为“ABO血型不合肾移植”的书籍。在文章中，首席研究员Takahashi描述了历史、日本患者和移植物存活数据更新、抗原分子和抗体、适应症和围手术期评估和管理、免疫抑制、皮质外免疫调节、移植和脾切除术的标准手术方法、感染控制、临床病理学研究和病例报告以及未来展望。本文还提出了ABO血型不合肾移植排斥反应病理学指标的新策略，并对肾移植中致敏前状态和急性排斥反应高危人群进行了评估，我们建立了检测抗肾小球内皮细胞抗体的细胞ELISA系统（AECA-GEC）和抗人脐静脉内皮细胞（AECA-HUVEG）在肾移植受者血清中。在22名受者的序贯血清检查中，AECA-GEC阳性组出现频率明显较高，这种现象表明，AECA-GEC阳性状态可能表明对器官的预致敏状态，提示肾小球内皮细胞上表达的特异性抗原可能引起移植肾微循环障碍，导致急性体液和细胞排斥反应，并为免疫抑制治疗提供了新的策略，包括清除获得性抗体和持续免疫抑制。高度致敏受者淋巴细胞产生抗体的免疫抑制。