P114 Repeat mismatch in renal transplantation: Is the original source of repeat mismatch more predictive than cPRA for antibody response post transplant?

The calculated panel reactive antibody (cPRA) value has been regarded as a predictor of rejection and allograft loss. Broad sensitization against HLA antigens characterized by a high cPRA value often results in intensification of induction and maintenance immunosuppression. Similarly, repeat mismatch HLA proteins between first transplants or pregnancy exposure and second transplants are thought to be potential stimuli for immune memory responses and increase the risk of rejection. We present two cases where original source of initial repeat mismatch proved to be a better predictor of antibody stimulation and rejection when compared to cPRA value. Case 1 is 47year old male who received a deceased donor renal transplant 12years after his first living related transplant failed with biopsy proven acute T-cell and chronic active antibody mediated rejection. His cPRA at the time of the second transplant was 99% and he received lymphocyte depleting ATG induction. There was a known repeat mismatch antigen at the Cw1 locus with his previous allograft and second transplant. Post-transplant HLA antibody testing done via Luminex bead assay did not demonstrate evidence of Cw1 antibody synthesis. Creatinine remains stable at 100umol/L 1year post transplant. Case 2 is 45year old female who underwent her first living unrelated renal transplant with an initial cPRA value of 0%. She underwent non-lymphocyte depleting induction with Basiliximab. She was known to have multiple repeat mismatches between previous pregnancy antigen exposure and her renal allograft at Class I (A2 epitope, B62) and Class II (DR7, DQ2, DQA02:01, DPB04:01) antigens. One year post transplant, she developed severe antibody mediated and cell mediated rejection resulting in graft loss. Post-transplant antibody testing demonstrated A2 epitope donor-specific antibodies and denovo DQ7 donor-specific antibody. The current cases illustrate that the source of repeat mismatch in second renal transplants may be more predictive of antibody response and rejection than magnitude of cPRA value. In particular, repeat mismatch antigens between pregnancy exposure as the initial sensitizing may be a stronger predictor of alloimmune recognition and rejection than repeat mismatches from a previous allograft in recipients undergoing retransplantation.