Eplet mismatches associated with de novo donor-specific HLA antibody in pediatric kidney transplant recipients.

Optimizing amino acid (eplet) histocompatibility at first transplant decreases the risk of de novo donor-specific antibody (dnDSA) development and may improve long-term graft survival in pediatric kidney transplant recipients (KTR). We performed a retrospective analysis of pediatric KTR and their respective donors to identify eplets most commonly associated with dnDSA formation. Eplet mismatch analysis was performed in a cohort of 125 pediatric KTR-donor pairs (2006–2018). We determined the prevalence of each eplet mismatch and quantified the percentage of exposed patients who developed dnDSA for each mismatched eplet. Recipient median age was 14 (IQR 8–17) years with a racial distribution of 42% Black, 48% Caucasian, and 5.6% Middle-Eastern. Median eplet load varied significantly by recipient race, Black 82 (IQR 58–98), White 60 (IQR 44–81) and Other 66 (IQR 61–76), p = 0.002. Forty-four percent of patients developed dnDSA after median 37.1 months. Compared to dnDSA− patients, dnDSA+ patients had higher median eplet load, 64 (IQR 46–83) vs. 77 (IQR 56–98), p = 0.012. The most common target of dnDSA were eplets expressed in HLA-A*11 and A2 in Class I, and HLA-DQ6 and DQA5 in Class II. The most commonly mismatched eplets were not the most likely to result in dnDSA formation. In a racially diverse population, only a subset of eplets was linked to antibody formation. Eplet load alone is not a sufficient surrogate for eplet immunogenicity. These findings illustrate the need to optimize precision in donor selection and allocation to improve long-term graft outcomes.