Application of HLA molecular level mismatching in ethnically diverse kidney transplant recipients receiving a steroid-sparing immunosuppression protocol

Defining HLA mismatch at the molecular compared with the antigen level has been shown to be superior in predicting alloimmune responses, although data from across different patient populations is lacking. Using HLA-Matchmaker, HLA-EMMA and PIRCHE-II, this study reports on the association between molecular mismatch (MolMM) and de novo DSA (dnDSA) in an ethnically diverse kidney transplant population receiving a steroid sparing immunosuppression protocol.51/419(12.2%) patients had dnDSA. De novo DSA were seen more frequently with males, primary transplants, patients receiving tacrolimus monotherapy and unfavourably HLA matched transplants. There was a strong correlation between MolMM load and antigen mismatch, although significant variation of MolMM load existed at each antigen mismatch. MolMM loads differed significantly by recipient ethnicity, although ethnicity alone was not associated with dnDSA. On multivariate analysis, increasing MolMM loads associated with dnDSA, whilst antigen mismatch did not. De novo DSA against 8 specific epitopes occurred at high frequency. 47/51(92.1%) dnDSA patients underwent a pre-treatment biopsy, 21/47(44.7%) having evidence of alloimmune injury.MolMM has higher specificity than antigen mismatching at identifying recipients who are at low risk of dnDSA whilst receiving minimalist immunosuppression. Immunogenicity consideration is important, with more work needed on identification, especially across different ethnic groups.