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We have assessed whether  HLA  immunogenicity as defined by differences in donor–recipient  HLA  amino‐acid sequence (amino‐acid mismatch score,  AMS ; and eplet mismatch score, Ep MS ) and physicochemical properties (electrostatic mismatch score,  EMS ) enables prediction of allosensitization to  HLA , and also prediction of the risk of an individual donor–recipient  HLA  mismatch to induce donor‐specific antibody ( DSA ).  HLA  antibody screening was undertaken using single‐antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of  AMS , Ep MS , and  EMS  on the development of allosensitization (calculated reaction frequency [ cRF ]) and  DSA  was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that  AMS  (odds ratio [ OR ]: 1.44 per 10 units, 95%  CI : 1.02–2.10, p = 0.04) and  EMS  ( OR : 1.27 per 10 units, 95%  CI : 1.02–1.62, p = 0.04) were independently associated with the risk of developing sensitization to  HLA  ( cRF  > 15%).  AMS , Ep MS , and  EMS  were independently associated with the development of  HLA ‐ DR  and  HLA ‐ DQ DSA , but only  EMS  correlated with the risk of  HLA ‐A and ‐B  DSA  development. Differences in donor–recipient  HLA  amino‐acid sequence and physicochemical properties enable better assessment of the risk of  HLA ‐specific sensitization than conventional  HLA  matching.

american journal of transplantation

Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor–Recipient  HLA  Amino Acid Sequence and Physicochemical Disparities Than Conventional  HLA  Matching