Introduction: Kidney transplantation is the preferred treatment for children with ESKD, but long-term graft survival remains challenging. Donor-specific antibodies (DSAs) are a key risk factor for late allograft dysfunction. Beyond conventional HLA matching, HLA eplet mismatches, especially at HLA-DQ and HLA-DR loci, have been linked to increased dnDSA formation and rejection in adult patient but such as report is scarce in paediatric cohort.
Aims: To determine correlation between HLA class I and II eplet Mismatches, dnDSA development in single centre cohort of paediatric KTRs.
Methodology: Children under 18 years who underwent kidney transplantation at our center from September 2016 to June 2024 were included. Exclusion criteria were pre-transplant DSA, prior desensitization, multi-organ transplantation, missing HLA or clinical data. Nine loci (HLA-A/B/C, -DRB1/3/4/5, -DQA1/-DQB1) high-resolution typing for 26/81 cases that lacked typing for donor or recipient, an in-house imputation pipeline was used to obtain high resolution typing results. For all included cases, dnDSA at 3, 6, 12 months, 3 and 5 years were analysed. HLA molecular mismatch (HLAMM) analysis, including eplet mismatch sum and single-molecule eplet mismatch, was performed using HLA Matchmaker v4.0, with risk categorization based on established cut-offs. Fishers exact test and log-rank test were used to assess variable associations and time to event data, respectively.
Results: After excluding cases with insufficient clinical details or meeting exclusion criteria, 81 out of 110 children were included in the analysis. Using cut-offs established by Wiebe and Nickerson for HLAMM risk assessment, we identified a strong association between HLA-DQA1/DQB1 eplet mismatch sum score (high risk: ≥11 epMM) and dnDSA at three- and six-months post-transplant (OR=6.33, Fisher’s p=0.07). We also observed lower freedom from DSA in the high-risk group (77.8%) compared to the low risk group (88.9%, log-rank p = 0.16). 

Conclusion: In a cohort of 81 pediatric kidney transplant patients we show that HLA-DQA1/DQB1 eplet mismatch sum score is associated with early dnDSA development, similar to the previous report in adult kidney cohort.