血清胶原代谢标志物作为弥漫性系统性硬皮病潜在诊断工具的研究：一项横断面研究。
Serum biomarkers of collagen turnover as potential diagnostic tools in diffuse systemic sclerosis: A cross-sectional study.
机构信息
Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark.
出版信息
PLoS One. 2018 Dec 3;13(12):e0207324. doi: 10.1371/journal.pone.0207324. eCollection 2018.
BACKGROUND
Systemic sclerosis (SSc) is characterized by excessive fibrosis throughout the body. This leads to the release of extracellular matrix (ECM) fragments into circulation, where they may be quantified as biomarkers. The objectives were to investigate levels of ECM turnover biomarkers and the diagnostic power of these.
METHODS
Diffuse SSc patients (n = 40) fulfilling the ACR/EULAR 2013 classification criteria and asymptomatic controls were included. Patients were divided into early (<2 years of symptoms; n = 20) and late (>10 years of symptoms; n = 20) diffuse SSc. Biomarkers of type I (C1M), III (C3A, C3M), IV (C4M), V (C5M) and VI (C6M) collagen degradation and type I (PRO-C1), II (PRO-C2), III (PRO-C3), IV (PRO-C4), V (PRO-C5) and VI (PRO-C6) collagen formation were measured in serum. Repeated measures ANOVA was used to test for differences in biomarker levels and the area under the receiver operating characteristic curve (AUC) was used to investigate the ability of the biomarkers to separate groups.
RESULTS
In early diffuse SSc, formation biomarkers of type III, IV, V and VI collagen were significantly increased compared to asymptomatic controls (p<0.0001). Moreover, in early diffuse SSc formation biomarkers of type III, V and VI collagen were significantly increased compared to late diffuse SSc (p = 0.0006, 0.003 and 0.004, respectively). Type I (p<0.0001), III (C3M: p = 0.001, and C3A: p = 0.02), IV (p<0.0001) and VI (p<0.0001) collagen degradation biomarkers significantly increased in early diffuse SSc compared to controls. C4M, C6M, PRO-C4, PRO-C5 and PRO-C6 had an AUC of >0.85 when assessing asymptomatic controls vs. diffuse SSc. Biomarkers of type VI collagen (PRO-C6 and C6M) turnover had the best separation with an AUC's of >0.90.
CONCLUSION
Formation biomarkers of ECM turnover were shown to be significantly different between asymptomatic controls and diffuse SSc. This pilot study suggest that serological biomarkers of the ECM turnover is potentially applicable in SSc.
背景
系统性硬化症（SSc）的特征是全身过度纤维化。这导致细胞外基质（ECM）片段释放到循环中，在循环中可以将其量化为生物标志物。目的是研究 ECM 周转率生物标志物的水平及其诊断能力。
方法
纳入符合 ACR/EULAR 2013 分类标准的弥漫性 SSc 患者（n = 40）和无症状对照者。患者分为早期（症状<2 年；n = 20）和晚期（症状>10 年；n = 20）弥漫性 SSc。测量血清中 I 型（C1M）、III 型（C3A、C3M）、IV 型（C4M）、V 型（C5M）和 VI 型（C6M）胶原降解以及 I 型（PRO-C1）、II 型（PRO-C2）、III 型（PRO-C3）、IV 型（PRO-C4）、V 型（PRO-C5）和 VI 型（PRO-C6）胶原形成的生物标志物。采用重复测量方差分析比较生物标志物水平的差异，并采用接收者操作特征曲线下面积（AUC）比较各标志物的分组能力。
结果
早期弥漫性 SSc 中，III、IV、V 和 VI 型胶原的形成生物标志物与无症状对照者相比显著升高（p<0.0001）。此外，早期弥漫性 SSc 中 III、V 和 VI 型胶原的形成生物标志物与晚期弥漫性 SSc 相比显著升高（p = 0.0006、0.003 和 0.004）。与对照组相比，早期弥漫性 SSc 中 I 型（p<0.0001）、III 型（C3M：p = 0.001，C3A：p = 0.02）、IV 型（p<0.0001）和 VI 型（p<0.0001）胶原降解生物标志物显著升高。评估无症状对照者与弥漫性 SSc 时，C4M、C6M、PRO-C4、PRO-C5 和 PRO-C6 的 AUC>0.85。VI 型胶原（PRO-C6 和 C6M）转换的生物标志物具有最高的分离度，AUC>0.90。
结论
无症状对照者与弥漫性 SSc 之间 ECM 周转率的形成生物标志物有显著差异。该初步研究表明，ECM 周转率的血清生物标志物在 SSc 中可能具有应用潜力。
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