Becker Mike Oliver, Radic Mislav, Schmidt Katrin, Huscher Dörte, Riedlinger Arne, Michelfelder Marissa, Meisel Christian, Ewert Ralf, Burmester Gerd-Rüdiger, Riemekasten Gabriela
equal contribution.
University Hospital Zürich, Dept of Rheumatology, Zürich, Switzerland.
Sarcoidosis Vasc Diffuse Lung Dis. 2019;36(4):274-284. doi: 10.36141/svdld.v36i4.7612. Epub 2019 May 1.
To identify serum cytokines which predict mortality and/or disease progression in patients with systemic sclerosis, especially with pulmonary involvement.
Serum cytokines (IL-6, IL-7, IL-8, IL-10, CCL2, CCL4, TGF-β, TNF-α) were measured in 125 SSc patients, who were recruited and observed in our outpatient clinic. Of these, 60 had pulmonary involvement, classified as either interstitial lung disease (ILD, 43 patients), pulmonary arterial hypertension (PAH, 7 patients) or pulmonary hypertension and ILD (PH-ILD, 10 patients). The association of serum cytokines with clinical features was analysed and their correlation with BAL cytokines measured in a subset of SSc patients with ILD.
Serum cytokines were detected at different levels: high (TGF-β, median 287.5 pg/ml; CCL2, median 89.7 pg/ml; CCL4, median 104.2 pg/ml), low (IL-6, median 3.2 pg/ml; IL-7 median 2.3 pg/ml; IL-8, median 5.2 pg/ml; TNF-α, median 0 pg/ml but with a bimodal distribution) and very low (IL-10, median 0.4 pg/ml). IL-6 and IL-7 were predictive for death in a Cox regression analysis in all SSc patients as well as in all patients with pulmonary involvement; IL-6 was predictive for mortality in SSc-ILD patients. In a multivariate analysis, cytokine levels could also predict a change in lung function, e.g. IL-7 was a predictor for a decline of diffusion capacity (DLCO) by 20 or 30% in ILD patients. In a subset of ILD patients, serum cytokines were compared to BAL cytokines, but revealed only few correlations.
In conclusion, the analysis of serum cytokines implicates a role as biomarkers, distinct from BAL.
确定可预测系统性硬化症患者，尤其是合并肺部受累患者死亡率和/或疾病进展的血清细胞因子。
对在我们门诊招募并观察的125例系统性硬化症（SSc）患者测定血清细胞因子（白细胞介素-6（IL-6）、白细胞介素-7（IL-7）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、趋化因子配体2（CCL2）、趋化因子配体4（CCL4）、转化生长因子-β（TGF-β）、肿瘤坏死因子-α（TNF-α））。其中60例有肺部受累，分为间质性肺疾病（ILD，43例患者）、肺动脉高压（PAH，7例患者）或肺动脉高压合并ILD（PH-ILD，10例患者）。分析血清细胞因子与临床特征的关联，并分析其与部分ILD型SSc患者支气管肺泡灌洗（BAL）细胞因子的相关性。
血清细胞因子检测到不同水平：高水平（TGF-β，中位数287.5 pg/ml；CCL2，中位数89.7 pg/ml；CCL4，中位数104.2 pg/ml）、低水平（IL-6，中位数3.2 pg/ml；IL-7中位数2.3 pg/ml；IL-8，中位数5.2 pg/ml；TNF-α，中位数0 pg/ml但呈双峰分布）和极低水平（IL-10，中位数0.4 pg/ml）。在所有SSc患者以及所有有肺部受累的患者中，Cox回归分析显示IL-6和IL-7可预测死亡；IL-6可预测SSc-ILD患者的死亡率。多因素分析中，细胞因子水平还可预测肺功能变化，例如IL-7是ILD患者弥散功能（DLCO）下降20%或30%的预测指标。在部分ILD患者中，将血清细胞因子与BAL细胞因子进行比较，但仅发现少数相关性。
总之，血清细胞因子分析表明其作为生物标志物具有一定作用，与BAL不同。
