Impact of HLA eplet mismatch load in immunological outcomes after living donor kidney transplantation

Abstract

IntroductionHLA eplets mismatches (eMM) have been associated with negative kidney outcomes after transplantation, such as the development of de novo donor-specific antibody (dnDSA), antibody-mediated rejection (ABMR), and early graft loss. This study aimed to evaluate the clinical effects of the HLA eMM load on dnDSA development, ABMR, renal function, allograft survival and graft loss. Material and methodsThis retrospective study involved 159 living donor kidney transplant patients categorized into groups based on antigen HLA mismatches assessed traditionally and HLA eMM load. Patients had followed for at least one year. The EpViX online program was used to evaluate the HLA eMM load. Cox models were constructed to assess the risk of graft loss. Kaplan-Meier survival curves were carried out. The analyses had performed using the R program and p < 0.05 was considered significant. ResultsFrom all 159 patients, 28 (17.6%) lost their allografts. Rejection episodes occurred in 37.1% of patients, 13.6% of whom were ABMR. Patients with rejection episodes had higher HLA-AB (p = 0.032) and HLA-DR (p = 0.008) HLA eMM load, HLA-AB (p = 0.006) and HLA-DR (p = 0.009) antigens mismatches, and higher proportions of the following eMM in the HLA-DR locus: 70R eMM (p = 0.015), 70RE (p = 0.015), 74E (p = 0.015) and 48Q (p = 0.047). In multiple models, the presence of HLA-DR 70qq eMM (HR 3.75, 95% CI 1.47; 9.55) add an increase in creatinine levels at 1-year (HR 3.87, 95% CI 2.30, 6.53) were associated with the risk of graft loss. ConclusionThe HLA eMM load was related to episodes of rejection and allograft loss. The HLA-DR eMM was most strongly associated with a worse immunologic outcome than eMM mismatches for HLA-AB.