ArticleFrontiers in immunology2026
A pre-emptive risk model for acute rejection in liver transplantation: an immunopharmacologic biomarker panel combining CD4+ T-cell profiling and tacrolimus exposure.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Acute cellular rejection (ACR) is a T cell-driven event in liver transplantation. Current monitoring relies on detecting graft injury, lacking tools for pre-emptive risk assessment based on the patient's real-time immune status. Methods: We developed an immunopharmacologic risk model in a retrospective cohort of 98 liver transplant recipients (18 with biopsy-proven ACR). The model integrated peripheral CD4+ T-cell percentage (flow cytometry) and tacrolimus trough level. Firth-penalized logistic regression was used for model development, with internal validation via bootstrapping. Results: The parsimonious model, comprising only CD4+ T-cell percentage and tacrolimus level, demonstrated good discrimination (AUC 0.774, 95% CI 0.674-0.874) and calibration. Critically, lead-time analysis revealed the model provided a median warning window of 8 days (IQR: 3.5 days) prior to biochemical injury onset. It offered significant incremental value over monitoring tacrolimus alone (AUC 0.774 vs. 0.694, ΔAUC=0.080, p=0.007) or CD4+ T cells alone (AUC 0.774 vs. 0.733, ΔAUC=0.041, p=0.014). Conclusion: We identify and validate a novel, clinically actionable immunopharmacologic biomarker panel for ACR. This model enables pre-emptive risk stratification by capturing the high-risk confluence of immune activation and subtherapeutic immunosuppression, paving the way for personalized immunotherapy in transplant recipients.
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