Single antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and SAB testing of day of transplant serum as 1) unsensitized; PRA=0 (n= 178), 2) 3rd party sensitized; no DSA (n=363), or 3) donor sensitized; with DSA (n=46), and studied rejection rates, death censored graft survival (DCGS), and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p<0.0001), but not with PRA in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p<0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p=0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.

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Recent registry data suggest that host-versus-graft alloreactions mediated by anti-donor human leukocyte antigen (HLA) antibodies in recipients of adult allogeneic hematopoietic stem cells or single-unit umbilical cord blood (UCB) contribute to the risk of graft failure. The present study evaluated the impact of anti-HLA antibodies on engraftment and unit predominance in 126 double UCB (dUCB) recipients. Eighteen dUCB recipients were identified with at least 1 of 2 UCB units recognized by anti-HLA antibodies directed against donor antigens (DSAs). Overall, 9 of 12 patients who had DSAs against one of the two UCB units composing the graft and 5 of 6 who had DSAs against both units engrafted. The cumulative incidence of engraftment was similar in patients with and without DSAs (83% vs. 78%). Thus, our data do not support the negative effect of anti-HLA antibodies on engraftment at least in the setting of cyclosporine and mycophenolate mofetil and the conditioning regimens employed at the University of Minnesota and argue against routine screening for use in graft selection prior to dUCB transplantation. Further studies are required to fully understand the value of anti-HLA antibody testing in dUCB graft selection and its impact on transplantation outcomes.

Quantification of plasma C4d+ microvesicles provides information about presence of AMR, its severity and response to treatment in transplant patients.