Inflammatory profile of induced sputum composition in systemic sclerosis and comparison with healthy volunteers

SCIENTIFIC REPORTS(2021)

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摘要
Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared. In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-beta, IL-8, TNF-alpha, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%). The IS of SSc patients had a lower weight than HV (p<0.05, p<0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p<0.0001), TGF- (p<0.05), IL-8 (p<0.05), YKL-40 (p<0.0001) and MMP-7 (p<0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p<0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%) (r==- 0.53, p<0.01), FVC (%) (r=- 0.51, p<0.01) and annualized KCO (%) (r=0.57, p<0.05), between IS TGF-beta levels and annualized FEV-1 (%) (r==- 0.57, p<0.05), between IS IGFBP-2 levels and annualized KCO (%) (r=0.56, p<0.05). Our study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-beta, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-beta and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.
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