CRTAC1: a novel indicator of lung involvement in systemic sclerosis

Objectives Interstitial lung disease (ILD) is the most frequent cause of mortality in patients with systemic sclerosis (SSc). Cartilage acidic protein-1 (CRTAC1), secreted by alveolar type-2 epithelial cells, is a potential biomarker of lung health. This study explores CRTAC1's role in SSc, focusing on pulmonary involvement. Methods We collected plasma samples from 76 SSc patients (65 females, limited cutaneous (lc)SSc : 45, diffuse cutaneous (dc)SSc : 31, ILD : 43, all fulfilled the 2013 ACR/EULAR criteria) and 89 healthy individuals (HC, 37 females). Patients were examined and assessed for the European Scleroderma Study Group (ESSG) activity score, modified Rodnan skin score (mRSS), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), diffusing capacity for carbon monoxide (DLCO) and Medsger Disease Severity Scale (DSS). CRTAC1 levels were measured using the CRTAC1 IQ-ELISA (Ray Biotech). Results CRTAC1 levels in plasma were lower in SSc patients compared with HC (p< 0.001). CRTAC1 was decreased in SSc patients with ILD compared with SSc patients without ILD (p= 0.027). Linear modelling showed negative association of CRTAC1 with DSS pulmonary involvement (p= 0.016, β=-2.46) and ESSG activity score (p= 0.047, β=-2.022), and a positive association with DLCO (p= 0.065, β = 1.87), FEV1 (p= 0.1, β = 1.622) and FVC (p= 0.072, β = 1.83). CRTAC1 levels were also decreased in SSc patients with gastrointestinal (p= 0.002) and joint (p= 0.006) involvement and pulmonary arterial hypertension (p= 0.05). Conclusion Systemic levels of CRTAC1 are decreased in SSc patients, especially among those with ILD, reduced lung function, and elevated disease activity. Our findings establish CRTAC1 as a promising biomarker for pulmonary involvement in SSc.