University of Groningen, University Medical Centre Groningen, Department of Internal Medicine, Division of Vascular Medicine, Groningen, the Netherlands.
University of Groningen, University Medical Centre Groningen, Department of Internal Medicine, Division of Vascular Medicine, Groningen, the Netherlands.
EBioMedicine. 2023 Dec;98:104883. doi: 10.1016/j.ebiom.2023.104883. Epub 2023 Nov 22.
Systemic sclerosis-interstitial lung disease (SSc-ILD) is the leading cause of death in patients with SSc. There is an unmet need for predictive biomarkers to identify patients with SSc at risk of ILD. Previous studies have shown that interferon (IFN) pathways may play a role in SSc. We assessed the use of C-X-C motif chemokine ligand 10 (CXCL10) as a predictive biomarker for new onset of ILD in patients with SSc.
One-hundred-sixty-five (Female, N = 130) patients with SSc (SSc-ILD, N = 41) and 13 (Female, N = 8) healthy controls were investigated retrospectively. CXCL10 protein levels were measured by ELISA. We performed log rank analysis with baseline CXCL10 serum levels. CXCL10 nanoString data from lung tissues obtained from transplanted patients with SSc-ILD were extracted. Fifteen (Female, N = 10) patients with SSc (SSc-ILD, N = 7) were recruited for bronchoalveolar lavage (BAL) procedure. Lung fibroblasts were treated with BAL-fluid or serum from patients with SSc with or without ILD. Inflammatory/fibrotic genes were assessed.
Serum CXCL10 levels were higher in patients with SSc-ILD compared to SSc patients without ILD [Median (IQR):126 pg/ml (66-282.5) vs. 78.5 pg/ml (50-122), P = 0.029, 95% CI: 1.5 × 10 to 0.4284]. Survival analysis showed that baseline CXCL10 levels >78.5 pg/ml have a 2.74-fold increased risk of developing new onset of ILD (Log-rank: P = 0.119) on follow-up. CXCL10 levels in BAL supernatant were not different in patients with SSc-ILD compared to SSc without ILD [76.1 pg/ml (7.2-120.8) vs. 22.3 pg/ml (12.1-43.7), P = 0.24, 95% CI: -19.5 to 100]. NanoString showed that CXCL10 mRNA expression was higher in inflammatory compared to fibrotic lung tissues [4.7 (4.2-5.6) vs. 4.3 (3.6-4.7), P = 0.029]. Fibroblasts treated with SSc-ILD serum or BAL fluids overexpressed CXCL10.
Clinical, transcriptomic, and in vitro data showed that CXCL10 is potentially involved in early SSc-ILD. More research is needed to confirm whether CXCL10 can be classified as a prospective biomarker to detect patients with SSc at higher risk of developing new onset ILD.
This collaborative project is co-financed by the Ministry of Economic Affairs and Climate Policy of the Netherlands utilizing the PPP-allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships (PPP-2019_007). Part of this study is financially supported by Sanofi Genzyme (NL8921).
系统性硬皮病-间质性肺病（SSc-ILD）是硬皮病患者死亡的主要原因。目前需要预测性生物标志物来识别有ILD 风险的 SSc 患者。先前的研究表明干扰素（IFN）途径可能在 SSc 中发挥作用。我们评估了 C-X-C 基序趋化因子配体 10（CXCL10）作为 SSc 患者新发间质性肺病的预测性生物标志物的作用。
回顾性调查了 165 名（女性，N=130）硬皮病患者（SSc-ILD，N=41）和 13 名（女性，N=8）健康对照者。通过 ELISA 测量 CXCL10 蛋白水平。我们对基线 CXCL10 血清水平进行对数秩分析。从患有 SSc-ILD 的移植患者的肺组织中提取了 CXCL10 nanoString 数据。招募了 15 名（女性，N=10）硬皮病患者（SSc-ILD，N=7）进行支气管肺泡灌洗（BAL）程序。用 BAL 液或 SSc 患者的血清处理肺成纤维细胞，有无 ILD。评估炎症/纤维化基因。
与无 ILD 的 SSc 患者相比，SSc-ILD 患者的血清 CXCL10 水平更高[中位数（IQR）：126 pg/ml（66-282.5）比 78.5 pg/ml（50-122），P=0.029，95%CI：1.5×10至 0.4284]。生存分析表明，基线 CXCL10 水平>78.5 pg/ml 时，新发 ILD 的风险增加 2.74 倍（Log-rank：P=0.119）。与无 ILD 的 SSc 患者相比，SSc-ILD 患者的 BAL 上清液中 CXCL10 水平无差异[76.1 pg/ml（7.2-120.8）比 22.3 pg/ml（12.1-43.7），P=0.24，95%CI：-19.5 至 100]。NanoString 显示，与纤维化肺组织相比，炎症性肺组织中 CXCL10 mRNA 表达更高[4.7（4.2-5.6）比 4.3（3.6-4.7），P=0.029]。用 SSc-ILD 血清或 BAL 液处理的成纤维细胞过度表达 CXCL10。
临床、转录组和体外数据表明，CXCL10 可能参与了早期 SSc-ILD。需要进一步研究以确认 CXCL10 是否可以归类为预测性生物标志物，以检测有新发 ILD 风险的 SSc 患者。
本合作项目由荷兰经济事务和气候政策部共同出资，利用生命科学与健康领域的高级部门提供的公私伙伴关系津贴（PPP-2019_007）来促进公私伙伴关系。本研究的一部分得到了赛诺菲 Genzyme（NL8921）的资助。
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