Correlation between serological biomarkers of extracellular matrix turnover and lung fibrosis and pulmonary artery hypertension in patients with systemic sclerosis
Correlation between serological biomarkers of extracellular matrix turnover and lung fibrosis and pulmonary artery hypertension in patients with systemic sclerosis
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DOI：
10.1111/1756-185x.13804
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发表时间：
2020-02-05
影响因子：
2.5
通讯作者：
Tanaka, Yoshiya
中科院分区：
文献类型：
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作者：
Kubo, Satoshi;Siebuhr, Anne Sofie;Tanaka, Yoshiya
目的探讨胶原降解/转换的血清学标志物作为系统性硬化症（SSc）患者器官受累的血清学标志物的价值。使用9种血清学生物标志物评价I型至VI型胶原蛋白（不包括II型胶原蛋白）的周转率。器官受累，如间质性肺疾病（ILD），肺动脉高压（PAH），食管动力障碍，下消化道病变，关节挛缩和手指溃疡，进行了评估和相关的血清生物标志物。结果在多种血清学胶原蛋白周转的生物标志物，C5 M的平均水平高于SSc（3.9 ng/mL）比健康受试者（2.6 ng/mL）。此外，SSc中的PRO-C6（12.6 ng/mL vs 5.4 ng/mL）和C6 M（26.0 ng/mL vs 16.7 ng/mL）高于对照组。改良Rodnan皮肤评分与PRO-C3和PRO-C6相关。ILD患者血清C6 M水平明显升高。此外，PAH患者的血清PRO-C3、PRO-C6和C6 M水平较高。使用高水平的这些生物标志物作为PAH的风险因素表明，所有PAH患者均具有高水平的风险因素。值得注意的是，三分之二的患者血清PRO-C3，PRO-C6和C6 M值高于各自的截止values.Conclusion我们的研究表明，胶原周转异常，特别是VI型胶原，不仅是重要的病理皮肤硬化，但也在器官受累。这些胶原蛋白周转的生物标志物可能在临床上用作SSc器官受累的生物标志物。
Objective To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc).Methods Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover, excluding type II collagen, were evaluated using nine serological biomarkers. Organ involvement, such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), esophageal motility disorder, lower gastrointestinal lesions, joint contractures and digital ulceration, were evaluated and correlated with serum biomarkers.Results Among multiple serological biomarkers of collagen turnover, the mean level of C5M was higher in SSc (3.9 ng/mL) than healthy subjects (2.6 ng/mL). In addition, PRO-C6 (12.6 ng/mL vs 5.4 ng/mL) and C6M (26.0 ng/mL vs 16.7 ng/mL) were higher in SSc than the controls. The modified Rodnan skin score correlated with PRO-C3 and PRO-C6. Serum level of C6M was higher in patients with ILD. Furthermore, serum levels of PRO-C3, PRO-C6, and C6M were higher in patients with PAH. The use of high levels of these biomarkers as risk factors of PAH showed that all patients with PAH had high levels of risk factors. Of note, two-third of patients with serum PRO-C3, PRO-C6 and C6M values above the respective cut-off values had PAH.Conclusion Our study indicated that collagen turnover abnormality, especially type VI collagen, is not only important pathologically in skin sclerosis but also in organ involvement. These biomarkers of collagen turnover are potentially clinically useful as biomarkers of organ involvement in SSc.