Human CLAD singlecell

Rationale:Chronic lung allograft dysfunction (CLAD) is the leading cause of late-stage failure in lung transplant recipients, characterized by progressive airway fibrosis and graft dysfunction. Early detection is crucial for improving outcomes, but reliable biomarkers remain limited. Fibroblast activation protein (FAP), a marker of activated fibroblasts, is implicated in fibrotic diseases; however, its role in CLAD is not well understood.Objective:To investigate the role of FAP as an early biomarker for CLAD by evaluating its expression in murine and human CLAD models.Methods:FAP expression was evaluated in murine and human CLAD models. In a murine lung transplantation model, single-cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC) were performed at baseline, day 7, and day 28 post-transplantation. Human lung tissues, including donor lungs and CLAD specimens, were analyzed using scRNA-seq, IHC, and image-based quantification. FAP expression in transbronchial lung biopsy (TBLB) samples was examined to assess its utility as a predictive biomarker.Measurements and MainResults:FAP expression was significantly upregulated in fibroblasts in murine and human CLAD models compared to controls. In murine lungs, FAP expression increased as early as day 7 and remained elevated through day 28. In human CLAD specimens, FAP positivity was higher in fibroblast clusters and detectable before clinical CLAD diagnosis.Conclusions:FAP is a promising early diagnostic marker for CLAD, with significant upregulation correlating with fibrotic remodeling. Its potential as a therapeutic target warrants further investigation in clinical trials to improve early detection and treatment of CLAD.