Which is more important for predicting de novo DSA production in donor-sensitized kidney transplant recipients, B-cell epitope or T-cell epitope analysis?

De novo donor-specific antibodies (dnDSA), particularly those against human leukocyte antigen (HLA) class II, can cause kidney allograft rejection, resulting in poor prognosis. Recently, HLA matching at both B-cell and T-cell epitopes, assessed by eplet mismatches and predicted indirectly recognizable HLA epitopes (PIRCHE) score, respectively, has been reported to be associated with dnDSA production. It remains unclear how these epitopes are involved in transplant immunology and how the results of the analysis can be applied in clinical practice. This study aimed to elucidate whether the significance of these analyses differed depending on the presence or absence of　donor-specific sensitization history. This retrospective cohort study of 691 living donor kidney transplants without preformed DSA included (A) potentially sensitized recipients due to pregnancy (n = 112) and (B) unsensitized recipients (n = 579). Twelve (10.7 %) and 93 (16.1 %) patients developed class II dnDSA in (A) and (B), respectively. Multivariate analysis revealed PIRCHE-II score, and acute T-cell mediated rejection (ATCMR) history were significant in both cohorts, but number of eplet mismatches was found significant in (B) but not (A). T-cell epitope analysis might be more effective in predicting dnDSA production via memory response in potentially sensitized recipients, although both B- and T-cell epitope analyses are important in the primary immune response of unsensitized patients. Although further analysis including transplant sensitization history is needed, the results may provide useful insights into donor allocation and personalized immunosuppression.