Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

Abstract

Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA.

The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation: a case series

“…1 HLA-DPB1 expression information based on the linkage between the HLA-DPB1 expression marker rs9277534 and HLA-DPB1 alleles as described by the group of EW Petersdorf [21,22]. 2 One case with presence of 96K 2 DSA instead of 84DEAV DSA.…”

“…In the Eurotransplant region, HLA-A, -B, -C, -DR, -DQ antigens and antibodies are entered into the Eurotransplant Network Information System (ENIS) and used for the allocation of solid organs whereas HLA-DP typing is not routinely performed. As a consequence, little is known about the impact of HLA-DP mismatches (MM) and antibodies on outcome, despite the high probability that a donor is mismatched for HLA-DP, even if a donorrecipient pair is identical at all classical loci [2,3].…”

Detection of HLA Antibodies in Organ Transplant Recipients – Triumphs and Challenges of the Solid Phase Bead Assay

“…The additional sensitivity provided by this method has enabled the detection of HLA antibodies in potential transplant patients which are not detectable by other means, particularly CDC (24, 26–29). This increased sensitivity has enabled improvement in the success rate of retransplant patients due to the detection of HLA presensitization as a result of previous grafts and the subsequent avoidance of the relevant HLA specificities on second grafts particularly for DP specificities that are not detected by other methods (31). …”

Humoral immunity in renal transplantation: epitopes, Cw and DP, and complement‐activating capability – an update

“…As most patients with DP antibodies also have anti‐DR and or DQ antibodies, the role of DP specifically has been hard to assess . High‐resolution typing and epitope analysis by HLA Matchmaker have allowed identification of patients with isolated anti‐DP antibodies that have suffered AMR and GL . A highly sensitized retransplant mismatched only at DPA1 and DPB1 with low‐level HLA‐DP DSA was reported .…”

“…High‐resolution typing and epitope analysis by HLA Matchmaker have allowed identification of patients with isolated anti‐DP antibodies that have suffered AMR and GL . A highly sensitized retransplant mismatched only at DPA1 and DPB1 with low‐level HLA‐DP DSA was reported . Despite a negative B‐cell FCXM, the graft rapidly developed AMR that was shown to be caused by intra‐allele epitope spreading and inter‐allele epitope sharing with post‐transplant sera reacting to previously unreactive eplets.…”