Exploring fibroblast activation protein as an early biomarker in chronic lung allograft dysfunction

Question Chronic lung allograft dysfunction (CLAD) is the leading cause of late graft failure after lung transplantation. Fibroblast activation protein (FAP) is selectively upregulated in activated fibroblasts under fibrotic conditions.

We asked whether FAP expression is increased in CLAD and whether it can serve as an early diagnostic marker. Materials and methods We performed single-cell RNA sequencing on two murine orthotopic lung transplant models (C57BL/6->C57BL/10 and BALB/c->C57BL/6) and human lung tissue from five controls and five patients with CLAD.

We quantified FAP expression by immunohistochemistry in transbronchial biopsies from 240 lung transplant recipients (62 with CLAD and 178 without CLAD). Receiver-operating characteristic curves determined an optimal FAP-positive area threshold.

Kaplan - Meier analysis and Cox proportional hazards models assessed the association between FAP positivity and CLAD. Results In both murine and human single-cell data, FAP expression was confined to pathogenic fibroblast subsets and was significantly elevated in CLAD.