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

TL;DR

This study identifies PDGFA and TGFB as potential blood biomarkers for early and accurate diagnosis of interstitial lung disease in connective tissue diseases.

Contribution

The study introduces PDGFA and TGFB as novel biomarkers for diagnosing connective tissue disease-related interstitial lung disease.

Findings

Lower PDGFA, TGFB1, and TGFB2 expression differentiates RA-ILD from RA-nonILD patients.

TGFB2 expression helps identify SSc-ILD patients with a specific cut-off.

PDGFA and TGFB2 expression can distinguish IM-ILD from IPF.

Abstract

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. PDGF and TGFB are the main profibrotic genes. We evaluated PDGFA, TGFB1, TGFB2, and TGFB3 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 PDGFA, TGFB1, and TGFB2 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 TGFB2 expression compared to SSc-nonILD patients, with a cut-off of <0.0018 identifying ILD in SSc. PDGFA and TGFB2 expression discriminated IM-ILD from IPF acting as accurate diagnostic biomarkers with cut-offs of >0.0166 and >0.001547, respectively. PDGFA and TGFB2, as well as TGFB2 and TGFB3 expression were associated with RA-ILD and SSc-ILD prognosis, respectively. PDGFA and TGFB are promising blood biomarkers with clinical value for the early and accurate CTD-ILD diagnosis.

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