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强直性脊柱炎的特征是几种不同的金属蛋白酶衍生胶原种类的周转率增加:一项横断面研究。

Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study.

机构信息

Cartilage Biology and Biomarkers, R&D, Nordic Bioscience, Hovedgade 207, 2730 Herlev, Denmark.

出版信息

Rheumatol Int. 2012 Nov;32(11):3565-72. doi: 10.1007/s00296-011-2237-8. Epub 2011 Nov 16.

Abstract

Ankylosing spondylitis (AS) is characterized by gradual cementation of the vertebrae, a process that is described by excessive extracellular matrix remodeling. Specific matrix metalloproteinase (MMP)-derived collagen fragments are released to the circulation, and measurement of those might act as biomarkers of ankylosis. The aim of the study was to investigate the diagnostic value of five novel assays measuring different collagen species. Five newly developed ELISAs measuring MMP-degraded collagen fragments in serum of 40 AS patients and 40 age-matched controls were measured: collagen type I (C1M), type II (C2M), type III (C3M), type IV (C4M) and type VI (C6M) as well as the bone formation marker osteocalcin. The levels of the five collagen neoepitopes were significantly higher in AS patients, except for osteocalcin. Cartilage degradation (C2M) was only significantly correlated with the basement membrane (C4M) in the AS patients. In contrast, C3M was significantly correlated with all of the other collagen markers. The highest diagnostic value was achieved when combining the C2M, C3M and C6M markers, AUC 87% (P < 0.0001). Moreover, a combination of the markers correlated with the clinical mSASS score (P = 0.004, R = 0.44). Novel and unique biomarkers of tissue remodeling may provide diagnostic value and aid in understanding of the AS pathology. Each of the biomarkers tells a unique story, and by combining them in a panel there, we found a strong correlation with mSASSS. We speculate that such panel will be a valuable tool for monitoring patients as effect of treatment, for the prediction of responders and for diagnostic purposes.

摘要

强直性脊柱炎(AS)的特征是脊柱逐渐融合,这一过程被描述为细胞外基质的过度重塑。特定的基质金属蛋白酶(MMP)衍生的胶原蛋白片段被释放到血液循环中,测量这些片段可能作为强直性脊柱炎融合的生物标志物。本研究旨在探讨五种新的测量不同胶原种类的检测方法的诊断价值。在 40 例 AS 患者和 40 名年龄匹配的对照者的血清中测量了五种新开发的 ELISA,分别为:I 型胶原(C1M)、II 型胶原(C2M)、III 型胶原(C3M)、IV 型胶原(C4M)和 VI 型胶原(C6M)以及骨形成标志物骨钙素。除骨钙素外,AS 患者的五种胶原新表位水平均显著升高。软骨降解(C2M)仅与 AS 患者的基底膜(C4M)显著相关。相反,C3M 与所有其他胶原标志物均显著相关。当联合 C2M、C3M 和 C6M 标志物时,诊断价值最高,AUC 为 87%(P<0.0001)。此外,标志物的组合与临床 mSASS 评分相关(P=0.004,R=0.44)。组织重塑的新型独特生物标志物可能具有诊断价值,并有助于理解 AS 病理学。每种生物标志物都讲述了一个独特的故事,通过将它们组合成一个面板,我们发现与 mSASSS 有很强的相关性。我们推测,这样的面板将是一种有价值的工具,可用于监测患者的治疗效果、预测应答者和诊断目的。

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