P157 Accelerated graft loss due to non-complement fixing donor-specific antibody against a single DP epitope

Abstract

Aim The clinical significance of donor-specific antibody (DSA) solely to DP antigens remains controversial. Here we report a case of accelerated graft loss attributed to DSA against a single DPB epitope which was exacerbated by the “peanut butter” phenomenon observed with the solid-phase single antigen bead (SAB) assays. Methods A 48-yo white female with history of ESRD due to hypertension received her 3rd renal transplant (TX) from a deceased donor with 5/6 ABDR mismatch and a 100% cPRA. Her other sensitizations included a pregnancy and multiple transfusions. Results Despite the presence of DSA to DPB1 ∗ 02:01 at 7100 MFI, TX was proceeded in light of clearly negative flow crossmatches (FCXM). Post-TX urine output initially improved but trended down on post-operative day (POD) 2 with elevated serum creatinine ⩾ 6 mg/dL. While SAB on POD3 indicated a decline of DP2 DSA to 4200 MFI, biopsy revealed a Banff IA rejection, with peritubular capillaritis and endothelial cell and vascular injury, suggestive of humoral components. Subsequent SAB on POD13 showed the addition of de novo DSA to B37 at 4300 MFI. Despite immediate intervention with ATG/IVIG/Rituxan/plasmapheresis, the patient developed a profound septic syndrome and a nephrectomy was performed on POD24. Allograft biopsy showed strong evidence of AMR with diffuse cortical necrosis and hemorrhage, arterial thromboses, intimal arteritis, with C4d+ in the peritubular capillaries. Epitope analysis suggested the preexisting DP DSA was in fact directed to a single epitope, 56EE, shared amongst 9 beads comprising 6 DPB1 alleles (02:01/04:02/10:01/18:01/28:01), thereby inadvertently diluting the actual DSA titer as shown on individual beads (“the peanut butter effect”). While it was not being detected by FCXM, the cumulative pre-TX MFI of the DP DSA was indeed > 65,000. Retrospective testing indicated that this DP DSA was never complement fixing, suggesting an involvement of antibody dependent cell-mediated cytoxicity. An intermediate level of anti-AT1R antibody was detected post-TX, which may have further accelerated the graft rejection process. Conclusions This case illustrates the deleterious effect of DSA solely to DP antigens. Epitope analysis may facilitate a more accurate assessment of the actual DSA titer, especially for the highly sensitized patients.