The changing role of antibody testing in transplantation

Although it was established in the 1980's that positive crossmatches associated with adverse transplant outcomes were those due to HLA specific antibodies, the cell-based assays for determining antibody specificity were time consuming, laborious, and moderately specific and sensitive. Technological advances now permit much more rapid and thorough antibody characterization. While no single assay can identify all anti-HLA antibodies in a patient's serum, the repertoire of specificities that can be defined is impressive and continues to improve. By using complimentary assays, most predominant specificities can be defined in even very highly sensitized patients. Perhaps, more critical, the sensitivity of solid phase immunoassays, which in some cases surpasses that of cell-based flow cytometry, provides a new level of assurance in the detection of humoral sensitization. The impact of these changes in antibody testing is already being felt in transplantation, providing a better evaluation of the level and breadth of sensitization prior to transplantation and greatly facilitating the success of humoral desensitization protocols. Thorough antibody identification can also provide a "virtual crossmatch" or a profile of incompatible donors defined by unacceptable antigens. An approach using the frequencies of unacceptable antigens to derive the probability of incompatible donors will likely be a feature of revised renal allocation for sensitized patients in the US. A compelling body of data is also accumulating proving the efficacy of monitoring for the recurrence or de-novo production of anti-donor HLA specific antibodies after transplantation. The possibility of early detection of humoral rejection in time for effective clinical intervention may offer a means to combat the inexorable loss of grafts to chronic rejection. Looking further into the future, as extensive antibody definition and monitoring are more universally applied, the ability to rule out HLA specific antibodies as a cause of graft loss will certainly also help determine the role of non-HLA antibodies in the outcome of solid organ and hematopoietic stem cell transplantation.