High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis
High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis
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DOI：
10.1016/j.chest.2016.03.004
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发表时间：
2016-08-01
期刊：
影响因子：
9.6
通讯作者：
Molberg, Oyvind
中科院分区：
文献类型：
--
作者：
Hoffmann-Vold, Anna-Maria;Tennoe, Anders Heiervang;Molberg, Oyvind
目的：系统性硬化症（SSc）患者进行性间质性肺疾病（ILD）的早期鉴别标志物是急需的。与肺部炎症有关的趋化因子CCL 18是一个有趣的候选者，但数据并不一致。我们的目的是评估CCL 18水平在一个大的，前瞻性的，CCL 18队列与纵向，配对数据集肺功能和肺fibrosis.METHODS：血清从奥斯陆大学医院SSc队列（n = 298）和健康对照组（n = 100）进行了分析CCL 18酶免疫法。高浓度CCL 18（>53 ng/mL）的定义是使用从健康对照受试者中获得的血清中的平均值加上2 SD作为截止值。高和低CCL 18亚群之间FVC的年下降率存在显著差异（13.3%和4.7%; P = 0.016），肺纤维化的年进展率也存在显著差异（0.9% [SD，2.9]和0.2% [SD，1.9]）。在高CCL 18和早期疾病（< 3年）的患者中观察到年FVC下降> 10%（21%）和年纤维化进展（1.2%）的最高发生率。在多变量分析中，CCL 18与随访时FVC年下降> 10%（OR，1.1; 95%CI，1.01-1.11）和FVC < 70%（OR，3.1; 95%CI，1.08-8.83）相关。生存分析显示，与低CCL 18患者相比，高CCL 18患者的5年和10年累积生存率降低（分别为85%和74%，而低CCL 18患者的5年和10年累积生存率分别为97%和89%; P = 0.001）。结论：该前瞻性队列的结果强化了高CCL 18可作为早期识别SSc中进行性ILD的标志物的概念。
OBJECTIVE: Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis.METHODS: Sera from the Oslo University Hospital SSc cohort (n = 298) and healthy control subjects (n = 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff.RESULTS: High serum CCL18 was identified in 35% (105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3% and 4.7%; P = .016), as did the annual progression rate of lung fibrosis (0.9% [SD, 2.9] and 0.2% [SD, 1.9]). Highest rates of annual FVC decline > 10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10% (OR, 1.1; 95% CI, 1.01-1.11) and FVC < 70% at follow-up (OR, 3.1; 95% CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85% and 74%, compared with 97% and 89%, respectively; P = .001).CONCLUSIONS: The results from this prospective cohort reinforce the notion that high CCL18 may serve as a marker for early identification of progressive ILD in SSc.