Bridging the gap: Correlating virtual crossmatch assessments with post-transplant immunologic outcomes

The virtual crossmatch (VXM) is a widely implemented tool for assessing immunological risk using donor HLA typing and a recipient's antibody profile. Several studies have documented the efficacy and advantages of the VXM. Most studies validate the accuracy of the VXM by showing correlation with flow crossmatch (FXM) results. However, true utility lies in correlation with transplant outcome and humoral immune response. In this study, we compared the VXM assessment, reported as VXM acceptable or unacceptable, to post-transplant outcome, donor-specific antibody development or resurgence, and FXM results. Overall, a VXM that was deemed acceptable correlated with fewer post-transplant adverse events compared to a VXMunacceptable. Kidney recipients with VXM unacceptable were significantly more likely to demonstrate memory HLA-DSA (p = 0.019), develop antibody-mediated rejection (AMR, p = 0.020), and develop AMR associated with HLA-DSA (p = 0.006) compared to kidney recipients with acceptable VXMs. Heart recipients showed similar trends although the results were not statistically significant due to small size. 94.4 % of VXM acceptable were also negative on FXM, and only 1.1 % of patients with acceptable VXMs benefited from a retrospective FXM. Our findings support the VXM as a reliable alternative to the FXM in most cases and identify situations where the FXM remains beneficial.