The development of donor-specific antibodies (DSA) has a significant impact on graft outcome in solid organ transplantation. Mismatched HLAs are recognized directly and indirectly by the recipient immune system. Both pathways occur in parallel and result in the generation of plasma cells, DSA, cytotoxic and T helper lymphocytes. Here, we present the results of an analysis of the epitope load of mismatched HLAs in a cohort of 220 lung transplant recipients using two in silico algorithms, HLAMatchmaker and PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes). De novo DSA (dnDSA) were detected by single antigen bead assays. The percentage of recipients who developed dnDSA was significantly higher in the group of patients who received lung transplants with a mismatching score above the detected threshold than in the group of patients who received lung transplants with a mismatching score below the threshold.In a multivariate Cox proportional hazard analysis, the PIRCHE-II score appeared to be a superior predictor of dnDSA formation. In addition, PIRCHE-II technology was shown to be useful in predicting separate dnDSA1 and dnDSA2 formation. We conclude that both algorithms can be used for the evaluation of the epitope load of mismatched HLAs and the prediction of DSA development in lung transplant recipients.

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