Abstract
The significance of human leukocyte antigen (HLA) epitopes in predicting kidney transplant outcomes is not yet sufficiently explored. We conducted a retrospective study of 47 patient-donor pairs after their first kidney transplant. The first cohort (n=28) consisted of recipients who developed de novo donor-specific antibodies (DSA), while the second cohort (n=19) comprised recipients in whom no antibody formation was detected even five years post-transplantation. Patients were selected according to the criteria of the 18th International HLA Workshop in Amsterdam 2022 (Project: Definition of Immunogenic Epitopes). The patients' serum specificity was determined using the Luminex single antigen test, and recipients and their donors were typed using second-generation sequencing. The definition of HLA epitopes was performed using the HLAmatchmaker algorithm.
Our results suggest that some HLA epitopes are more immunogenic than others. Epitopes 76ESI and 161D in class I HLA antigens elicited the strongest immune response, while positions 219W and 73TVS appeared to have low immunological risk. In class II HLA, 4 out of 5 of the most immunogenic positions were targeted against DQ antigens (30H, 52LL, 135G, and 45GV), with antibodies against epitope 30H appearing in 56% of discordant cases. Conversely, the least immunogenic positions were 87Y, 129Q, and 35FA, where no antibody formation occurred in any of the 30 cases combined. Our study suggests that pre-transplant HLA matching based on the analysis of HLA epitopes can provide important information about acceptable HLA mismatches and overall reduce the risk of DSA development while improving donor availability for highly HLA-sensitized patients.