A Comparison of HLA Molecular Mismatch Methods to Determine HLA Immunogenicity

AbstractBackgroundAntibody-mediated rejection is a major cause of premature graft loss in kidney transplantation. Multiple scoring systems are available to assess the HLA mismatch between donors and recipients at the molecular level, however, their correlation with the development of de novo donor-specific antibody (dnDSA) has not been compared in recipients on active immunosuppression.MethodsHLA-DRβ1/3/4/5/DQα1β1 molecular mismatch was determined using eplet analysis, amino acid mismatch, and electrostatic mismatch for 596 renal transplant recipients and correlated with HLA-DR/DQ dnDSA development. The molecular mismatch scores were evaluated in multivariate models of posttransplant dnDSA free survival.ResultsEplet mismatch correlated with amino acid mismatch and electrostatic mismatch (R2=0.85-0.96). HLA-DR dnDSA free survival correlated with HLA-DR eplet mismatch (HR 2.50 per 10 eplets mismatched, p

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