Trends in HLA Antibody Screening and Identification and Their Role in Transplantation

Cathi L Murphey; Thomas G Forsthuber


Expert Rev Clin Immunol. 2008;4(3):391-399. 

In This Article

Expert Commentary & Five-year View

The role of complement in antibody-mediated rejection has been the focus for many years now[44,45,46,47] and the new solid-phase assays have added another dimension to address this issue. Schonemann et al. described a novel flow-cytometric crossmatch that can distinguish complement-binding from noncomplement-binding antibodies.[48] Bartel and Bohmig reported on the incidence of complement-binding antibodies in the sera of patients, detected by using a modification of flow screening beads that could, possibly, be used as a tool to identify patients at risk for antibody-mediated rejection.[49] New adaptations of the Luminex platforms to investigate complement fixation in antibody identification have been described recently by Smith et al. These investigators showed that the presence of C4d-positive, donor-specific antibody(ies) was a predictor for poor graft outcome in cardiac transplantation.[50] While the focus of this review has been HLA antibodies and their role in transplantation, it is important to note that recent data suggest endothelial cell and MHC class I polypeptide-related sequence A antibodies may be associated with poor graft survival and more studies are needed to gain insight into their role in antibody-mediated rejection.[51,52]

The rapid development of new technologies will probably change the way we utilize HLA antibody testing for transplantation in the near future. While the new solid-phase technologies are clearly advantageous, they are still artificial systems that do not mimic the conformational aspects of MHC molecules. The ultimate technology would address the biological aspect of antigen-antibody binding. Highly sensitized patients will benefit from increased access to transplantation. Utilization of the 'virtual crossmatch' by HLA laboratories in the USA will allow for faster and easier organ allocation for organ-procurement organizations. Improvements in the multiplexing platforms and single-antigen bead technologies will overcome some of the limitations of the current assays and provide the most accurate and sensitive data that will directly translate into better patient care.


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