PIRCHE-II epitope burden associates with innate immune phenotypes after liver transplantation

Whether donor–recipient HLA epitope mismatch burden is associated with specific peripheral immune phenotypes in clinically stable liver transplant (LT) recipients remains unclear. In this exploratory translational study, we evaluated whether HLA epitope mismatch burden, quantified by the PIRCHE-II score, is associated with coordinated peripheral immune configurations in 14 clinically stable LT recipients. Prespecified biologically informed immune cell ratios spanning innate and adaptive compartments were analyzed within a constrained hierarchical framework using Benjamini–Hochberg false discovery rate correction across four primary endpoints; secondary exploratory analyses evaluated broader immune families using within-family correction. Higher PIRCHE-II scores were associated predominantly with innate immune phenotypes, particularly increased proportions of nonclassical monocytes and CD56 + CD16 high natural killer cells, representing the most robust associations across analytical frameworks, with directionally consistent but statistically attenuated associations observed in CD8 + CD38 + T cells and IgM + IgD + B-cell compartments in exploratory analyses. These associations occurred without evidence of overt systemic inflammation or major changes in absolute immune cell counts, indicating a qualitative, innate-predominant immune skewing rather than generalized immune activation. These findings support specific and consistent peripheral immune phenotypes associated with epitope mismatch burden in clinically stable LT recipients, although interpretation remains limited by the small sample size and exploratory design.