One of the earliest controversies in the field of transplantation, after the demonstration by Brent that the homograft (allograft) reaction was immunologic, was whether grafts are rejected by humoral or cellular mechanisms (1). Currently the cellular theory of graft rejection dominates. However, despite many attempts to detect the pretransplantation state of immunization by testing T lymphocyte function, only the humoral anti-HLA panel-reactive antibody (PRA*) test (2) has been effective in measuring alloimmunization. The clinical relevance of the humoral response was clearly demonstrated in 1969 in a study that showed that HLA antibodies can instantly kill an entire kidney (3). Two excellent reviews were published recently, showing that patients with pretransplantation anti-HLA PRA have an increased risk of graft failure (4, 5). Thus it is now routine to measure anti-HLA antibodies before transplantation. However posttransplantation monitoring of anti-HLA antibodies is not performed routinely. Recent advances in the techniques used to detect anti-HLA antibodies, as well as a substantial number of studies showing an association of posttransplantation anti-HLA antibodies with adverse events, suggest that such testing may be clinically useful as well as give some insight into the mechanism of graft rejection. In this review, we will describe advances in HLA antibody testing and recent studies to determine the relevance of posttransplantation HLA antibody in solid organ transplantation. We summarize the evidence that HLA antibodies developed after transplantation are associated with acute as well as chronic rejection of allografts.

On a historical note, the first posttransplantation antibody study was performed in 1968 on 24 patients who underwent transplantation in Richmond, Virginia (6). The presence of HLA antibodies detected by complement-dependent cytotoxicity (CDC) was associated with poor function of the kidney transplants. Early studies on the detection of HLA antibodies were based on the standard lymphocyte cytotoxicity test (7). Renewed interest in posttransplantation antibodies has been driven by enhancements in the CDC assay (8) and the recent development of more sensitive and specific ELISA (9, 10) and flow cytometry tests (11–14). Using these tests, the association of HLA antibodies with rejection is becoming clearer and stronger.