A New Approach for Achieving Earlier and More Accurate Diagnosis of Connective Tissue Disease-Related Interstitial Lung Disease: TGFB and PDGFA as Novel Promising Biomarkers

An early and accurate diagnosis of connective tissue diseases-related interstitial lung disease (CTD-ILD) is crucial for delaying lung fibrosis, but its unknown etiology and the limitations of clinical tools make it challenging for clinicians. <i>PDGF</i> and <i>TGFB</i> are the main profibrotic genes. We evaluated <i>PDGFA</i>, <i>TGFB1</i>, <i>TGFB2</i>, and <i>TGFB3</i> role in the diagnosis of ILD associated with rheumatoid arthritis (RA), systemic sclerosis (SSc), and inflammatory myopathies (IM). Blood was collected from 289 patients:33 RA-ILD, 31 SSc-ILD, 29 IM-ILD; and 22 RA-nonILD, 18 SSc-nonILD, 8 IM-nonILD; and 148 idiopathic pulmonary fibrosis (IPF). The relative expression was quantified by qPCR. Lower <i>PDGFA</i>, <i>TGFB1</i>, and <i>TGFB2</i> expression differentiated RA-ILD from RA-nonILD patients, acting as ILD early diagnostic biomarkers in RA with cut-offs of <0.01153, <0.3185, and <0.001410, respectively. SSc-ILD patients revealed decreased <i>TGFB2</i> expression compared to SSc-nonILD patients, with a cut-off of <0.0018 identifying ILD in SSc. <i>PDGFA</i> and <i>TGFB2</i> expression discriminated IM-ILD from IPF acting as accurate diagnostic biomarkers with cut-offs of >0.0166 and >0.001547, respectively. <i>PDGFA</i> and <i>TGFB2</i>, as well as <i>TGFB2</i> and <i>TGFB3</i> expression were associated with RA-ILD and SSc-ILD prognosis, respectively. <i>PDGFA</i> and <i>TGFB</i> are promising blood biomarkers with clinical value for the early and accurate CTD-ILD diagnosis.