P003 Successful kidney transplantation across positive crossmatches with strong donor-specific HLA-DP antibodies

Abstract

The role of anti-HLA-DP antibodies in renal transplantation is poorly defined. One of our kidney re-list candidates with 99% CPRA (+ many strong DP antibodies) received a kidney offer from a single DP1 mismatched deceased donor. The patient displayed strong DP1 antibodies (MFI = 10930) and thereby positive B cell pronase crossmatch (MCS = 125; cutoff is 120 MCS). Since the donor is highly matched and crossmatch was borderline positive, we move forward with this transplantation with anti-CD25 mAb induction and a single dose IVIG (2 g/kg) at day 1 post-tx. The graft was functioning and no rejection noticed in 6 month biopsy. The aim of the present study was to expand similar transplants for highly sensitized patients across DP donor-specific antibodies (DSA) with positive or negative B cell XM. 16 candidates (4 female listed for 1st tx, 6 females and 6 males listed for re-tx) with cPRA ranging from 75 to 100% (9 candidates had cPRA 100%) were transplanted with DP DSAs of greater than 5000 MFI (9 had MFI > 100,00). Retrospective FXM were done on 15 patients. Kidney biopsy data on 12 patients were evaluated for C4d deposition and AMR. One Lambda single antigen bead (SAB) assay was used to test HLA antibodies. 9 of 15 retrospective B FXM were positive, and the positive B FXM had DP DSAs of >10000 MFI (pronase MCS are generally ∼200). The levels of DP DSAs were plotted at pre- and post-tx (1 week, 1 month and 6 months) sera, which show significant decreases in DP DSAs in all 16 recipients (see figure). The 6 month protocol biopsy found no AMR in 9 recipients (8 were C4d- and 1 was C4d+), and C4d- AMR+ in 3 patients. One recipient developed de novo DSA to A32 (MFI = 14,000) but was undetectable at 6 months post-tx. The presence of HLA-DP antibodies particularly in broadly sensitized re-list candidates decrease the chance of finding a compatible donor. Results from this study show that patients can be transplanted across the HLA-DP DSAs without affecting graft survival, and therefore increasing access for broadly sensitized candidates.Download : Download high-res image (222KB)Download : Download full-size image