Donor/Recipient HLA Molecular Mismatch Scores Predict Primary Humoral and Cellular Alloimmunity in Kidney Transplantation

Donor/recipient molecular human leukocyte antigen (HLA) mismatch predicts primary B-cell alloimmune activation, yet the impact on de novo donor-specific T-cell alloimmunity (dnDST) remains undetermined. The hypothesis of our study is that donor/recipient HLA mismatches assessed at level may also influence a higher susceptibility to development posttransplant alloimmunity. In this prospective observational study, 169 consecutive kidney transplant recipients without preformed antibodies (DSA) and with high resolution typing were evaluated for scores using different informatic algorithms [amino acid mismatch, eplet MM, Predicted Indirectly Recognizable Epitopes (PIRCHE-II)]. Primary activation over first 2 years posttransplantation was by means both dnDSA dnDST single bead (SAB) IFN-γ ELISPOT assays, respectively. Also, predominant alloantigen presenting pathway priming DST contribution main alloreactive subsets further characterized in vitro . Pretransplantation, 78/169 (46%) DST+ whereas 91/169 (54%) DST−. At years, 54/169 (32%) patients showed detectable responses: 23/54 (42%) 31/54 (57%) persistently positive (persistDST+). 24/169 (14%) developed dnDSA. A strong correlation observed between three distinct they all accurately predicted formation, particular DQ locus. Likewise, incompatibility advent dnDST, especially when PIRCHE-II score (OR 1.014 95% CI 1.001–1.03, p=0.04). While pretransplant BPAR 5.18, CI=1.64–16.34, p=0.005) particularly T cell mediated rejection 5.33, CI=1.45–19.66, p=0.012), developing significantly risk subsequent formation (HR 2.64, CI=1.08–6.45, p=0.03). experiments unlike predominantly primed CD8+ direct cells, be activated indirect presentation, driven CD4+ cells an important proportion patients. De cellular alloreactivity seems precede humoral influenced poor matching.