Kidney transplant rejection despite zero eplet DR / DQ mismatch: A case report

Eplet mismatch (MM) quantification is a valuable tool for refining histocompatibility in kidney transplantation, especially at HLA-DR/DQ loci. However, zero MM at these loci does not ensure complete immunological safety. We report a 17-year-old male who received a living donor kidney transplant via the kidney paired donation (KPD) program. The donor had 0 eplet MMs at HLA-DR/DQ, with negative crossmatch and no pre-transplant donor-specific antibodies (DSAs). Despite this, the patient developed early mixed rejection-T cell-mediated (TCMR) and antibody-mediated (ABMR), and further analysis revealed DSAs targeting an HLA-C 80 K/77 N eplet. Combined treatment for TCMR and ABMR led to histological and functional improvement. This case illustrates the limitation of relying solely on HLA-DR/DQ eplet matching. Despite achieving 0 MM at these loci, the patient developed significant alloimmune injury. Molecular MM scores are useful predictive biomarkers, but they do not fully capture the complexity of immune responses in transplantation.