Monitoring of anti-HLA class I and II antibodies by flow cytometry in patients after first cadaveric kidney transplantation

While the relevance of pre-formed anti-human leukocyte antigen (HLA) antibo dies has been studied extensively, the role of anti-HLA class I and II anti bodies produced after cadaveric kidney transplantation is still a matter of discussion. As it has been proposed that they are involved in a considerab le number of cases, it should be investigated whether a post-transplant mon itoring 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 ant ibody detection and graft survival. We retrospectively investigated 59 pati ents after a first cadaveric kidney transplantation without known anti-HLA antibodies (complement-dependent cytotoxicity [CDC] testing). The panel rea ctivity was determined with a new highly sensitive and specific flow-cytome tric technique (Flow-PRA Screening Test(C), One Lambda, Canoga Park, USA) i n sequentially collected serum samples pre- and posttransplant. In patients with acute rejection episodes during the clinical course, the last sample prior to rejection, and in patients without rejection, the last sample prio r 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 cl inical 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-HL A antibodies were detectable in only 7/59 patients and a correlation betwee n 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 o f 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 lon ger CIT (p = 0.003). Whether the detection of anti-HLA class II antibodies in the early post-tra nsplant 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 episod es in patients after first cadaveric kidney transplantation.