Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in...

Anti-melanoma differentiation-associated gene five antibody positive (MDA5⁺) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5⁺ DM patients.

Plasma samples from 20 MDA5⁺ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5⁺ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA).

A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5⁺ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5⁺ DM.

This study provides novel insights into the pathogenesis of RP-ILD development in MDA5⁺ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.