Longitudinal serological assessment of type VI collagen turnover is related to progression in a real-world cohort of idiopathic pulmonary fibrosis

Jannie M B Sand,Thomas S Prior,Elisabeth Bendstrup,Henrik Jessen,Sarah R Rønnow,Peder Frederiksen,Diana J Leeming,Nils Hoyer,Morten A Karsdal,Saher B Shaker

doi:10.1186/s12890-021-01684-3

Abstract

BackgroundRemodeling of the extracellular matrix (ECM) is a central mechanism in the progression of idiopathic pulmonary fibrosis (IPF), and remodeling of type VI collagen has been suggested to be associated with disease progression. Biomarkers that reflect and predict the progression of IPF would provide valuable information for clinicians when treating IPF patients.MethodsTwo serological biomarkers reflecting formation (PRO-C6) and degradation (C6M) of type VI collagen were evaluated in a real-world cohort of 178 newly diagnoses IPF patients. All patients were treatment naïve at the baseline visit. Blood samples and clinical data were collected from baseline, six months, and 12 months visit. The biomarkers were measured by competitive ELISA using monoclonal antibodies.ResultsPatients with progressive disease had higher (P = 0.0099) serum levels of PRO-C6 compared to those with stable disease over 12 months with an average difference across all timepoints of 12% (95% CI 3–22), whereas C6M levels tended (P = 0.061) to be higher in patients with progressive disease compared with stable patients over 12 months with an average difference across all timepoints of 12% (95% CI − 0.005–27). Patients who did not receive antifibrotic medicine had a greater increase of C6M (P = 0.043) compared to treated patients from baseline over 12 months with an average difference across all timepoints of 12% (95% CI − 0.07–47). There were no differences in biomarker levels between patients receiving pirfenidone or nintedanib.ConclusionsType VI collagen formation was related to progressive disease in patients with IPF in a real-world cohort and antifibrotic therapy seemed to affect the degradation of type VI collagen. Type VI collagen formation and degradation products might be potential biomarkers for disease progression in IPF.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive worsening of lung function and a higher mortality rate than most cancers [1, 2]
Baseline characteristics A total of 178 patients diagnosed with idiopathic pulmonary fibrosis (IPF) were included in the current analyses and their baseline characteristics are summarized in Table 1 and Additional file 1: Table S1
Remodeling of the extracellular matrix (ECM) is a central mechanism in the progression of IPF, and remodeling of type VI collagen has been suggested to be associated with disease progression [20, 22]

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive worsening of lung function and a higher mortality rate than most cancers [1, 2]. IPF is progressive in nature, predicting the course of the disease in an individual patient is difficult [3, 4]. The antifibrotic therapies nintedanib and Jessen et al BMC Pulmonary Medicine (2021) 21:382 pirfenidone slow down the rate of decline in forced vital capacity (FVC) [5, 6]. The American Thoracic Society (ATS) recommends that future studies in pulmonary fibrosis should focus on finding new appropriate clinical endpoints, e.g. reflecting the degree of fibrosis and tissue turnover, to support functional assessments using FVC [10]. Biomarkers that reflect and predict the progression of IPF would provide valuable information for clinicians when treating IPF patients

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