Isolated Pre-existing HLA-DP Donor-Specific Antibodies are Associated With Poorer Outcomes in Renal Transplantation

INTRODUCTION: The importance of donor-specific antibodies (DSAs) in renal transplantation has long been recognized, but the significance of human leukocyte antigen (HLA)-DP antibodies remains less clear. We performed a retrospective single center study of renal transplants with pre-existing isolated HLA-DP-DSAs to assess clinical outcomes. METHODS: Twenty-three patients with isolated HLA-DP-DSAs were compared with 3 control groups as follows: standard immunological risk (calculated reaction frequency [cRF] < 85%, no current or historical DSA, no repeat mismatched antigens with previous transplants, n = 46), highly sensitized (cRF > 85%, n = 27), and patients with HLA-DP antibodies that were not donor-specific (n = 18). Univariate and multivariate analyses were performed comparing antibody-mediated rejection (ABMR)-free and graft survival. Factors in the final multivariable models included patient group, % cRF, B-cell flow crossmatch (BFXM) positivity and regrafts. RESULTS: Over a median follow-up of 1197 days, 65% of HLA-DP-DSA patients had ABMR on indication biopsies, and 30% of HLA-DP-DSA patients lost their graft. Pre-existing HLA-DP DSAs remained the single factor associated with ABMR after multivariable analysis (hazard ratio [HR] = 9.578, P = 0.012). Patients with HLA-DP DSAs had increased microvascular scores (P = 0.0346) and worse transplant glomerulopathy (P = 0.015) on biopsy compared with the standard immunological risk group. Furthermore, flow crossmatch (FXM) positivity did not help inform on the risk of graft failure or ABMR in patients with preformed DP-DSA. CONCLUSION: Transplants with pre-existing HLA-DP-DSAs should be considered high risk. Routine laboratory tests are unable to further risk stratify these patients. Recipients should be considered for intensified immunosuppression and closely monitored.