Müller-Steinhardt M, Fricke L, Kirchner H, Hoyer J, Klüter H
Institute of Immunology and Transfusion Medicine, University of Lübeck, School of Medicine, Germany.
Clin Transplant. 2000 Feb;14(1):85-9. doi: 10.1034/j.1399-0012.2000.140116.x.
While the relevance of pre-formed anti-human leukocyte antigen (HLA) antibodies has been studied extensively, the role of anti-HLA class I and II antibodies produced after cadaveric kidney transplantation is still a matter of discussion. As it has been proposed that they are involved in a considerable number of cases, it should be investigated whether a post-transplant monitoring is a sensitive parameter for the early diagnosis of acute rejection episodes. Additionally, it has been suggested that antibodies are a major cause for chronic rejection; thus, it would be of interest to correlate antibody detection and graft survival. We retrospectively investigated 59 patients after a first cadaveric kidney transplantation without known anti-HLA antibodies (complement-dependent cytotoxicity [CDC] testing). The panel reactivity was determined with a new highly sensitive and specific flow-cytometric technique (Flow-PRA Screening Test, One Lambda, Canoga Park, USA) in sequentially collected serum samples pre- and post-transplant. In patients with acute rejection episodes during the clinical course, the last sample prior to rejection, and in patients without rejection, the last sample prior to discharge, was analyzed. Furthermore, we analyzed 3-yr graft survival and several clinical parameters such as cold ischemia time (CIT). Twenty-four of 59 patients (41%) experienced acute rejections during the clinical course. Five of 59 died with a functioning graft within the first 3 yr. Seven of 54 patients, still alive after 3 yr, lost their graft. Anti-HLA antibodies were detectable in only 7/59 patients and a correlation between antibody positivity and acute rejections (p = 0.32 and 0.54 for anti-HLA class I and II, respectively) could not be identified (sensitivity 12.5 and 8.3%). However, we found a significant correlation between the detection of anti-HLA class II and graft loss within 3 yr (p = 0.005, specificity 97.9%). Additionally, anti-HLA class II positive patients had significantly longer CIT (p = 0.003). Whether the detection of anti-HLA class II antibodies in the early post-transplant phase is of great value for the identification of patients at high risk for early graft loss needs additional investigation. However, we found that anti-HLA antibodies are detectable only in a minority of unsensitized patients and we conclude that flow-cytometric monitoring with Flow PRA is not a sensitive parameter for the early diagnosis of acute rejection episodes in patients after first cadaveric kidney transplantation.
虽然预先形成的抗人白细胞抗原（HLA）抗体的相关性已得到广泛研究，但尸体肾移植后产生的抗HLA I类和II类抗体的作用仍存在争议。由于有人提出它们在相当多的病例中起作用，因此应该研究移植后监测是否是急性排斥反应早期诊断的敏感参数。此外，有人认为抗体是慢性排斥反应的主要原因；因此，将抗体检测与移植物存活情况相关联会很有意义。我们回顾性研究了59例首次进行尸体肾移植且无已知抗HLA抗体（补体依赖细胞毒性[CDC]检测）的患者。采用一种新的高灵敏度和特异性的流式细胞术（Flow-PRA筛选试验，美国加利福尼亚州卡诺加公园市One Lambda公司）测定移植前后序贯采集的血清样本中的群体反应性。对于临床过程中发生急性排斥反应的患者，分析排斥反应前的最后一份样本；对于未发生排斥反应的患者，分析出院前的最后一份样本。此外，我们分析了3年移植物存活率以及几个临床参数，如冷缺血时间（CIT）。59例患者中有24例（41%）在临床过程中发生了急性排斥反应。59例患者中有5例在最初3年内移植肾功能正常时死亡。54例3年后仍存活的患者中有7例失去了移植物。仅在59例患者中的7例检测到抗HLA抗体，且未发现抗体阳性与急性排斥反应之间存在相关性（抗HLA I类和II类的p值分别为0.32和0.54）（敏感性分别为12.5%和8.3%）。然而，我们发现抗HLA II类抗体的检测与3年内移植物丢失之间存在显著相关性（p = 0.005，特异性为97.9%）。此外，抗HLA II类阳性患者的CIT明显更长（p = 0.003）。移植后早期检测抗HLA II类抗体对于识别早期移植物丢失高风险患者是否具有重要价值需要进一步研究。然而，我们发现只有少数未致敏患者可检测到抗HLA抗体，并且我们得出结论，使用Flow PRA进行流式细胞术监测不是首次尸体肾移植患者急性排斥反应早期诊断的敏感参数。
