Circulating CTHRC1 levels are associated with IPF disease severity and survival

Abstract Objective Idiopathic pulmonary fibrosis (IPF) is a disease of high morbidity and mortality. We previously identified a novel subset of pathologic fibroblasts, characterized by CTHRC1 expression, uniquely present in fibrotic lung diseases. The aim of this study was to determine the association of serum CTHRC1 with clinical outcomes in IPF to assess its potential as a biologically relevant biomarker. Methods A retrospective longitudinal cohort study was performed utilizing two cohorts including a discovery cohort of 352 IPF patients from University of California San Francisco (UCSF) and a validation cohort of 1,152 IPF patients from the Pulmonary Fibrosis Foundation (PFF) as well as 41 healthy controls. Serum CTHRC1 was measured by ELISA and patients were stratified by quartiles of CTHRC1 for analysis. For a subset of patients, serial serum and lung CTHRC1 expression were measured. Associations between CTHRC1 and clinical outcomes, including baseline lung function, lung function trajectory, and transplant-free survival were assessed. Results Serum CTHRC1 was elevated in IPF patients compared to healthy controls (UCSF 31661 + 11651 and PFF 33916 + 14547 vs. 24409 + 8630pg/ml, p