From eplet annotation to time-resolved rejection risk

Antibody-verified eplet status should not be treated as a time-invariant rejection biomarker without longitudinal validation. The relevant sequence is baseline donor–recipient mismatch, emergence or persistence of donor-specific antibody, intervening injury or inflammation, treatment, and subsequent graft phenotype. Analyses should therefore anchor samples to transplant date and treatment changes, while separating stable graft function, non-rejection injury, and biopsy-defined rejection. Genetic matching scores may add baseline susceptibility information, but they cannot substitute for these evolving molecular and clinical contexts. The central test is whether eplet annotation improves discrimination of injury from rejection beyond antibody trajectory and sampling time.