Molecular biomarkers in idiopathic pulmonary fibrosis

Abstract

Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF.

Keywords: biomarker; diagnosis; prediction; pulmonary fibrosis.

Fig. 1.

Ideal qualities of molecular biomarkers for idiopathic pulmonary fibrosis. BAL, bronchoalveolar lavage; IPF, idiopathic pulmonary fibrosis; ILD, interstitial lung disease.

Fig. 2.

Core mechanisms and candidate molecular biomarkers for idiopathic pulmonary fibrosis (see text and Table 1). Pictured is the alveolar space (top, light blue), epithelial cell layer (tan), interstitial space (white), and capillary (bottom, red). Injury to the alveolar epithelium from a variety of inciting factors (dark blue box) leads to epithelial cell dysfunction, fibrogenesis/extracellular matrix (ECM) deposition, and immune dysregulation. Proposed molecular biomarkers of these processes include blood proteins, genomic markers, and blood cells (see light green boxes). cCK18, cleaved cytokeratin 18; CXCL, C-X-C chemokine ligand; ELMOD2, ELMO containing domain 2 gene mutations; EMT, epithelial-to-mesenchymal transition; ER, endoplasmic reticulum; HSP, heat shock protein; MMP, matrix metalloproteinase; KL6/MUC1, Krebs von den Lungen 6/mucin 1; MUC5B, mucin 5B promoter polymorphism; OPN, osteopontin; SPA, surfactant protein A; SPA2, surfactant protein A2 gene mutations; SPC, surfactant protein C gene mutations; SPD, surfactant protein D; TERT/TERC, telomerase gene mutations; TGF, transforming growth factor; TLR3, Toll-like receptor 3 gene mutation; TOLLIP, Toll-interacting protein gene mutations; Treg, regulatory T cell; UPR, unfolded protein response.