27-OR

Abstract

Aim To perform a retrospective analysis of the 3rd kidney transplant rejection with exclusive disparity at HLA-DP. Methods The 1st transplant, nearly completely mismatched, functioned well for 7 years but was rejected due to chronic allograft nephropathy. The 2nd transplant, completely matched except at DRB3 and DPB1, failed after 1 year with acute and chronic rejection. A 3rd kidney was completely matched except at DPA1*02:01 and DPB1*01:01. Although single antigen bead (SAB) analysis showed donor-specific alloantibodies (DSA) directed to DPA1*02:01 (3496-4024 MFI), both B and T flow crossmatches (FXM) were negative. Within 10 days the re-transplant underwent aggressive C4d+ acute antibody-mediated rejection (AMR; Banff 2a). Despite thymoglobulin therapy and 4 cycles of plasmapheresis, kidney failed within 6 months. At 30 days post-transplant, SAB assay revealed that DSA (directed to donor DPA1*02:01 and DPB1*01:01 bead) was IgG (9511 MFI) of IgG1 subclass (8664 MFI) with C1q binding function (22800 MFI). Results Epitope analysis showed that the 1st transplant shared DPA1*02:01 with the 3rd transplant while the 1st transplant DPB1*11:01 shared two epitopes (35YA, 84DEAV) with the 3rd donor DPB1*01:01. DSA response directed to just one epitope (111R) on DPA1*02:01 spread to other epitopes (83A, 51RA, 127P)(Fig. 1). Conclusions (1) DPA1 and DPB1 alleles may induce an aggressive acute AMR resulting in graft failure; (2) DSA directed to donor DPA1 allele may be undetected by FXM; (3) DPA1 and DPB1 alleles should be identified in donors of re-transplanted patients with DPA1/DPB1-directed Abs; and 4) epitope spreading and epitope sharing enhance FXM-undetectable DSA during acute AMR [Fig. 1].