Virtual Crossmatch: By Any Other Name

We thank Bray et al1 from the Emory group for praising our analysis of a vast amount of data and furthering the discussion on the relationship between physical crossmatch (PXM) and virtual crossmatch (VXM). We appreciate that assessing immunologic risk for transplant candidates is a complex process that will vary widely among laboratories, physicians, and transplant centers and will be affected by experience and resources. The goal of the University of California, Los Angeles (UCLA) Virtual Crossmatch Exchange is to provide participating laboratories with an opportunity to see and compare the results from many different laboratories with their own.2 We selected the flow crossmatch test as a comparator because it has been an important component of immunological risk assessment for transplantation for many years and is a familiar anchor for most laboratories.3 A positive PXM due to HLA antibodies may be considered a contraindication to transplantation and/or inform on the need for pre- or posttransplant therapeutic interventions. Therefore, it is rational that laboratories and their transplant centers assess the relationship between the VXM and PXM to guide their decision-making. In their Letter to the Editor, Bray et al state, “while the VXM has been used to predict a PXM, we disagree with the notion that a PXM result should be used to define the VXM.” They also state, “we disagree with the authors’ statement that correlating a VXM to a PXM result is critical.” These comments are surprising to us because confirming the accuracy of the VXM to predict the PXM was precisely what was done by Bray et al4 when they published the Emory Algorithm, which reported the probability of the VXM to predict a negative PXM. The UCLA Virtual XM Exchange assesses the capacity of the VXM to predict the PXM, not the other way around. Furthermore, the American Society for Histocompatibility and Immunogenetics standard D.5.3.8.1 states that the American Society for Histocompatibility and Immunogenetics–accredited laboratory must have a written policy to document criteria for and procedures to use in assessing prospective compatibility (ie, physical versus virtual crossmatch) for each transplant program it serves. As delineated in our article, the UCLA Virtual Crossmatch Exchange is not currently a proficiency test, and hence, the challenges are not graded because we recognize that laboratories will evaluate their results according to their processes. Instead, the challenges are educational exercises that allow laboratories to review aggregate results and provide insight to variability in reported responses using the same donor and recipient vignettes. As reported in our publication, despite the complexities, there is general agreement among laboratories as to their assessment of antibody specificity and strength and equivalence with the flow crossmatch in a virtual crossmatch exercise. Given the lack of standardization of solid-phase HLA antibody testing in the United States and the known impact of different protocols and serum treatments on the sensitivity and accuracy of antibody detection and antibody strength and titer, the UCLA Virtual Crossmatch Exchange provides useful mock clinical cases allowing laboratories to correlate VXM prediction using single-antigen class I and class II antibody tests to the actual PXM results.