HLA‐DPB1 molecular mismatches are risk factors for acute rejection and low 5‐year graft function in first kidney transplants

The study aimed to investigate the impact of HLA‐DPB1 allelic and molecular mismatches on the occurrence of acute rejection (AR) and low 5‐year graft function (5Y‐GF) in first kidney transplant (KT) recipients. This is a single center retrospective study of 130 deceased donor KT recipients transplanted between 2014 and 2016. HLA‐DPB1 allelic MM and the following molecular MM (mMM) were analyzed: expression MM with the high expression G allele in the donor; T cell epitope MM (TCE MM); epitope MM (EMM), considering all six hypervariable regions (EMM‐ABCDEF HVR), or only ABEF regions (EMM‐ABEF HVR); eplet MM (EpMM); antibody‐verified eplet MM (AbVer EpMM); and solvent accessible amino acid MM (SAMM). There was no association of allelic MM with AR or 5Y‐GF. The variables independently associated (Cox regression analyses) with AR were high donor final creatinine, nonpermissive TCE MM, ABCDEF EMM load ≥6, EpMM load ≥6; SAMM load ≥5, and AbVer EpMM load ≥3. No association between any HLA‐DPB1 mMM and 5Y‐GF was observed when all 130 transplant recipients were considered. However, when transplants from expanded criteria donors were excluded, independent associations were detected (logistic regression analyses) with AbVerEpMM load ≥2, SAMM load ≥7, cerebro‐vascular death, donor age, and AR. To our knowledge, this is the first study that shows that some HLA‐DPB1 mMM are associated with AR and low 5Y‐GF in a population of exclusively first kidney transplant recipients.