Rheumatology Department, CHU Liège, GIGA Research, ULiège, University Hospital of Liege, Domaine Universitaire du Sart-Tilman, B35, 4020, Liège, Belgium.
Pneumology Department, CHU Liège, GIGA Research, ULiège, Domaine Universitaire Sart Tilman, Liège, Belgium.
Sci Rep. 2021 May 21;11(1):10679. doi: 10.1038/s41598-021-87701-1.
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-β, IL-8, TNF-α, 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-β (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-β 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-β, 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-β 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.
系统性硬化症 (SSc) 是一种潜在的严重和致残性结缔组织疾病,尤其是在间质性肺病 (SSc-ILD) 的情况下。我们的研究目的是评估诱导痰 (IS) 中的剂量的潜在效用,并比较 SSc-ILD 和 SSc-非ILD 患者以及健康志愿者 (HV) 中的水平。还比较了 IS 和血清值。在一项前瞻性横断面分析中,我们研究了 25 名 SSc 患者、15 名 SSc-非ILD 患者和 10 名 SSc-ILD 患者的 IS 和血清,并与 25 名 HV 进行了比较。我们分析了痰细胞成分,并通过市售的免疫测定法对上清液和相应的血清进行了定量:IGFBP-1、IGFBP-2、IGFBP-3、TGF-β、IL-8、TNF-α、YKL-40、MMP-7 和 MMP-9。通过测定 FEV-1(%)、FVC(%)、DLCO(%)和 KCO(%)来研究肺功能。SSc 患者的 IS 重量低于 HV(p<0.05,p<0.01),但细胞数量无显著差异。与 HV 相比,SSc 患者的 IS 中 IGFBP-1(p<0.0001)、TGF-β(p<0.05)、IL-8(p<0.05)、YKL-40(p<0.0001)和 MMP-7(p<0.01)水平升高。与 HV 相比,仅 SSc 患者的血清 IL-8 水平升高(p<0.001)。无论是在 IS 还是血清中,SSc-ILD 和 SSc-非ILD 患者之间均未观察到差异。在 IS IL-8 水平和 FEV-1(%)(r=−0.53,p<0.01)、FVC(%)(r=−0.51,p<0.01)和年度 ∆KCO(%)(r=0.57,p<0.05)之间观察到相关性,在 IS TGF-β 水平和年度 ∆FEV-1(%)(r=−0.57,p<0.05)之间观察到相关性,在 IS IGFBP-2 水平和年度 ∆KCO(%)(r=0.56,p<0.05)之间观察到相关性。我们的研究表明,SSc 患者的 IS 中 IGFBP-1、TGF-β、IL-8、YKL-40 和 MMP-7 水平升高,这些分子已知与肺重塑和纤维化过程有关,SSc-ILD 和 SSc-非ILD 患者之间无明显差异。IL-8、TGF-β 和 IGFBP-2 与 SSc 患者的肺功能相关,这强调了其临床相关性。IS 分析代表了一种了解 SSc 患者肺部炎症过程的新方法。需要进行一项纵向研究来评估其病理生理相关性。