KL-6 而非 CCL-18 是系统性硬化症相关间质性肺病早期进展的预测因子。
KL-6 But Not CCL-18 Is a Predictor of Early Progression in Systemic Sclerosis-related Interstitial Lung Disease.
机构信息
From the Department of Internal Medicine, Division of Rheumatology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA; Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Japan.
G.A. Salazar, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; M. Kuwana, MD, PhD, Department of Allergy and Rheumatology, Nippon Medical School; M. Wu, MD, PhD, The University of Texas Health Science Center at Houston, McGovern Medical School; R.M. Estrada-Y-Martin, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; J. Ying, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; J. Charles, MS, The University of Texas Health Science Center at Houston, McGovern Medical School; M.D. Mayes, MD, MPH, The University of Texas Health Science Center at Houston, McGovern Medical School; S. Assassi, MD, MS, The University of Texas Health Science Center at Houston, McGovern Medical School.
出版信息
J Rheumatol. 2018 Aug;45(8):1153-1158. doi: 10.3899/jrheum.170518. Epub 2018 Jul 1.
OBJECTIVE
The 2 pneumoproteins, KL-6 and CCL-18, are promising biomarkers in systemic sclerosis (SSc)-related interstitial lung disease (ILD). Our goal was to determine their predictive significance for forced vital capacity % (FVC%) decline within the first year of followup in patients with early SSc-ILD.
METHODS
Early SSc patients with imaging-verified ILD enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort were included. Annualized rate of change in FVC% based on the baseline and followup measurement within 12-18 months was used as the surrogate outcomes for ILD progression.
RESULTS
Eighty-two early SSc-ILD patients with mean disease duration of 2.3 years were investigated. FVC% change ranged from -23% to 38%. Baseline KL-6 levels were higher in patients than healthy controls (p < 0.0001). Higher KL-6 levels were predictive of faster FVC% decline at the 1-year followup (r = -0.23, p = 0.037). Upon categorizing KL-6 using a previously published cutoff of 1273 U/ml, its predictive significance remained in the univariable model (b = -0.07, p = 0.01), indicating that patients with positive KL-6 had on average 7% more decline in annualized percent change of FVC%. Moreover, KL-6 remained an independent predictor after adjustment for sex, disease type, anti-Scl-70, and immunosuppressive treatment status in multivariable models. Although CCL-18 was higher in patients than controls (p < 0.001), its levels did not predict FVC decline rate (p = 0.458).
CONCLUSION
KL-6 but not CCL-18 is predictive of early SSc-ILD progression. KL-6 is a promising pneumoprotein that can contribute to SSc-ILD clinical trial enrichment.
目的
KL-6 和 CCL-18 这两种肺保护蛋白是系统性硬化症（SSc）相关间质性肺病（ILD）有前途的生物标志物。我们的目标是确定它们在早期 SSc-ILD 患者随访的第一年中对用力肺活量（FVC）%下降的预测意义。
方法
我们纳入了遗传学与硬皮病结局研究（GENISOS）队列中影像学证实的 ILD 的早期 SSc 患者。基于基线和 12-18 个月内随访测量的 FVC%的年变化率被用作 ILD 进展的替代结局。
结果
我们调查了 82 例早期 SSc-ILD 患者，平均病程为 2.3 年。FVC%的变化范围从-23%到 38%。与健康对照组相比，患者的 KL-6 水平更高（p<0.0001）。较高的 KL-6 水平预示着在 1 年随访时 FVC%下降更快（r=-0.23，p=0.037）。使用之前发表的 1273 U/ml 的截断值对 KL-6 进行分类后，其预测意义在单变量模型中仍然存在（b=-0.07，p=0.01），表明 KL-6 阳性的患者 FVC 的年化百分比变化平均下降 7%。此外，在多变量模型中，KL-6 在调整性别、疾病类型、抗 Scl-70 和免疫抑制治疗状态后仍然是独立的预测因子。虽然 CCL-18 患者比对照组更高（p<0.001），但其水平不能预测 FVC 下降率（p=0.458）。
结论
KL-6 但不是 CCL-18 可以预测早期 SSc-ILD 的进展。KL-6 是一种很有前途的肺保护蛋白，可以为 SSc-ILD 临床试验的富集做出贡献。
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