Flow cytometry crossmatching: The first 10 years

Abstract

In this review, we have briefly summarized the experience with the FCXM in the past 10 years. Amid confusing outcome data early on, a clearer picture is emerging by understanding the nature of the antibodies detected by the FCXM and defining their cellular targets. Numerous studies, especially the most recent, show significant survival differences between FCXM-positive and -negative first transplants, even though a few early studies did not. Moreover, in all studies the FCXM result has consistently shown itself to be important in the case of regrafts and sensitized recipients (Table 4). The variability of the survival data shows that the FCXM is by no means a perfect, or even well-understood, test at this time. To improve its usefulness, we need to define further the roles of the anti-donor antibodies that the FCXM detects: low-titer anti-donor antibodies and noncomplement-fixing antibodies. Furthermore, we need to define even more specifically the targets to which harmful antibodies bind. Perhaps equally important questions to ask are why certain anti-donor antibodies are not harmful to the donor graft and what factors determine their production. It is clear that the FCXM can detect transplants with potentially poor outcomes that the standard CXM misses, but at the cost of false positives. Our task in the next 10 years will be to improve on the sensitivity and specificity of the FCXM, and to integrate the FCXM into the changes in pretransplant and posttransplant immunologic monitoring. A shift in thinking should ensue about how best to use the results of crossmatches and other tests in the pretransplant workup. We should no longer look at these tests individually, but rather integrate their results as a whole into a cohesive cumulative transplant risk formula that will guide us in assessing the potential risk of any given donor-recipient pair. Finally, the role of FCXM in living-related transplants is currently undefined and deserves further careful evaluation.