The exquisitely sensitive single antigen bead (SAB) technique was shown to detect human leukocyte antigen (HLA) antibodies in sera of healthy male blood donors. Such false reactions can have an impact on critical decisions, especially with respect to the determination of unacceptable HLA-antigen mismatches in patients awaiting a kidney transplant. We tested pretransplant sera of 534 patients on the kidney waiting list using complement-dependent cytotoxicity (CDC), enzyme-linked immunosorbent assay (ELISA) and SAB in parallel. Evidence of HLA antibodies was obtained in 5% of patients using CDC, 14% using ELISA, and 81% using SAB. Among patients without history of an immunizing event, 77% showed evidence of HLA antibodies in SAB. In contrast 98% of these patients were negative in ELISA and CDC. In patients without an immunizing event, SAB-detected antibodies reacted not always weakly but with mean fluorescence intensity (MFI) values as high as 14 440. High-MFIvalue antibodies were found in some of these patients with HLA specificities that are rather common in general population, consideration of which would lead to unjustified exclusion of potential kidney donors. False SAB reactions can be unveiled by testing with additional antibody assays. Denial of donor kidneys to recipients based on HLA-antibody specificities detected exclusively in the SAB assay is not advisable.
Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.
HighlightsPretransplant DSA have a deleterious impact on graft survival only in the presence of high pretransplant serum levels of sCD30.The majority of patients with pretransplant DSA might be transplanted safely without special pretreatment measures.Kidney transplantation in the presence of donor-specific HLA antibodies (DSA) is associated with a high failure rate due to antibody-mediated rejection. Many centers avoid transplantations if DSA are present. Others perform such transplantations after removal of DSA by apheresis under potent immunosuppression.We provide strong evidence that DSA positive recipients reject their grafts at a high rate only if the immune activation marker sCD30 is also high, suggesting that T-cell help from an activated immune system is necessary for pretransplant DSA to exert a deleterious effect on the graft.High-risk patients with DSA and sCD30 may benefit from special treatment measures. The presence of DSA alone may not be deleterious.
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