McGovern Medical School, University of Texas Health Science Center at Houston.
McGill University, Montreal, Quebec, Canada.
Arthritis Rheumatol. 2017 Sep;69(9):1871-1878. doi: 10.1002/art.40171. Epub 2017 Aug 8.
There are few clinical predictors of the progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD). The purpose of this study was to examine the predictive significance of key cytokines for long-term progression of ILD and survival in 2 independent cohorts of patients with early SSc.
Plasma levels of 11 Th1/Th2 cytokines (interleukin-1β [IL-1β], IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor, CCL2, interferon-inducible T cell α chemoattractant, and interferon-γ-inducible 10-kd protein) were measured in 266 patients with early SSc in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) discovery cohort. Levels of CCL2, IL-10, and IL-6 were measured in 171 patients with early SSc in the Canadian Scleroderma Research Group (CSRG) replication cohort. The primary outcome measure was a decline in the forced vital capacity percent predicted (FVC%) value over time. A joint analysis of longitudinal FVC% values and survival was performed.
After adjustment for age, sex, and ethnicity, CCL2 and IL-10 were found to be significant predictors of ILD progression in the discovery cohort. Higher CCL2 levels predicted a faster decline in FVC% values (b = -0.57, P = 0.032), while higher IL-10 levels predicted a slower decline (b = 0.26, P = 0.01). A higher CCL2 value was also predictive of poorer survival (hazard ratio 1.76, P = 0.030). In the CSRG replication cohort, higher CCL2 levels predicted a faster decline in FVC% values (b = -0.58, P = 0.038), but neither IL-10 nor IL-6 had predictive significance. A higher CCL2 level also predicted poorer survival (hazard ratio 3.89, P = 0.037).
Higher CCL2 levels in the circulation were predictive of ILD progression and poorer survival in patients with early SSc, findings that support the notion that CCL2 has a role as a biomarker and potential therapeutic target.
系统性硬化症（SSc）相关间质性肺病（ILD）的进展鲜有临床预测因子。本研究旨在通过 2 个独立的早期 SSc 患者队列，检验关键细胞因子对ILD 长期进展和生存的预测意义。
在遗传学与硬皮病结局研究（GENISOS）的发现队列中，对 266 例早期 SSc 患者的 11 种 Th1/Th2 细胞因子（白细胞介素-1β [IL-1β]、IL-5、IL-6、IL-8、IL-10、IL-12、IL-13、肿瘤坏死因子、CCL2、干扰素诱导的 T 细胞α趋化因子和γ干扰素诱导的 10-kd 蛋白）的血浆水平进行了检测。在加拿大硬皮病研究组（CSRG）的复制队列中，对 171 例早期 SSc 患者的 CCL2、IL-10 和 IL-6 水平进行了检测。主要观察终点是用力肺活量占预计值的百分比（FVC%）值随时间的下降。对纵向 FVC%值和生存进行了联合分析。
在调整了年龄、性别和种族因素后，CCL2 和 IL-10 被发现是发现队列中ILD 进展的显著预测因子。较高的 CCL2 水平预示着 FVC%值下降速度更快（b=−0.57，P=0.032），而较高的 IL-10 水平预示着下降速度更慢（b=0.26，P=0.01）。较高的 CCL2 值还预示着生存率更差（风险比 1.76，P=0.030）。在 CSRG 复制队列中，较高的 CCL2 水平预示着 FVC%值下降更快（b=−0.58，P=0.038），但 IL-10 和 IL-6 均无预测意义。较高的 CCL2 水平也预示着生存率更差（风险比 3.89，P=0.037）。
循环中较高的 CCL2 水平可预测早期 SSc 患者的 ILD 进展和生存率较差，这一发现支持 CCL2 作为生物标志物和潜在治疗靶点的作用。
