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反映蛋白酶3和基质金属蛋白酶-12催化弹性蛋白降解的血液生物标志物,作为炎症性肠病内镜和临床疾病潜在的非侵入性替代标志物。

Blood-Based Biomarkers Reflecting Protease 3 and MMP-12 Catalyzed Elastin Degradation as Potential Noninvasive Surrogate Markers of Endoscopic and Clinical Disease in Inflammatory Bowel Disease.

作者信息

Pehrsson Martin, Domislovic Viktor, Alexdottir Marta Sorokina, Brinar Marko, Karsdal Morten Asser, Barisic Ana, Krznaric Zeljko, Mortensen Joachim Høg

机构信息

Biomarkers and Research, Nordic Bioscience A/S, 2730 Herlev, Denmark.

Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, 10000 Zagreb, Croatia.

出版信息

J Clin Med. 2023 Dec 19;13(1):21. doi: 10.3390/jcm13010021.

DOI:10.3390/jcm13010021
PMID:38202027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10779348/
Abstract

Chronic inflammation in inflammatory bowel disease (IBD) triggers significant extracellular matrix remodeling, including elastin remodeling, leading to severe clinical complications. Novel methods to assess intestinal tissue destruction may act as surrogate markers of endoscopic disease activity, relieving patients of invasive endoscopy. We explored the noninvasive blood-based biomarkers ELP-3 and ELM-12, measuring elastin degradation in IBD. In a study involving 104 Crohn's disease (CD), 39 ulcerative colitis (UC), and 29 healthy donors, we assessed these biomarkers' association with endoscopic and clinical disease activity using ELISA. Patients were evaluated based on the SES-CD and CDAI for CD patients and modified MES and partial Mayo for UC patients. ELP-3 and ELM-12 were elevated in patients with IBD. Discerning CD patients in endoscopic remission and mild from moderate to severe, ELP-3 provided an AUC of 0.69 and ELM-12 an AUC of 0.73. The ELP-3 biomarker was associated with UC patients and provided the highest diagnostic power of 0.87 for remission vs. active clinical disease. The data suggest an association of ELP-3 with active CD and ELM-12 with endoscopic remission in CD patients. Additionally, ELP-3 could identify UC patients with active clinical disease from patients in remission. The noninvasive biomarkers ELP-3 and ELM-12 could be potential surrogate biomarkers of elastin degradation and endoscopic and clinical disease markers.

摘要

炎症性肠病(IBD)中的慢性炎症会引发显著的细胞外基质重塑,包括弹性蛋白重塑,进而导致严重的临床并发症。评估肠道组织破坏的新方法可作为内镜疾病活动的替代标志物,从而使患者无需接受侵入性内镜检查。我们探索了基于血液的非侵入性生物标志物ELP-3和ELM-12,以测量IBD中的弹性蛋白降解情况。在一项涉及104例克罗恩病(CD)、39例溃疡性结肠炎(UC)患者以及29名健康捐赠者的研究中,我们使用酶联免疫吸附测定法(ELISA)评估了这些生物标志物与内镜及临床疾病活动的相关性。根据SES-CD和CDAI对CD患者进行评估,根据改良的MES和部分梅奥评分对UC患者进行评估。IBD患者的ELP-3和ELM-12水平升高。区分处于内镜缓解期的CD患者以及轻度与中度至重度患者时,ELP-3的曲线下面积(AUC)为0.69,ELM-12的AUC为0.73。ELP-3生物标志物与UC患者相关,对于缓解期与临床活动期疾病,其诊断能力最高,为0.87。数据表明,ELP-3与活动期CD相关,而ELM-12与CD患者的内镜缓解相关。此外,ELP-3可以区分处于临床活动期的UC患者与缓解期患者。非侵入性生物标志物ELP-3和ELM-12可能是弹性蛋白降解以及内镜和临床疾病标志物的潜在替代生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/7ce2d821adb3/jcm-13-00021-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/3a10dda42576/jcm-13-00021-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/805c0646b149/jcm-13-00021-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/1009bc1ed091/jcm-13-00021-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/7ce2d821adb3/jcm-13-00021-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/3a10dda42576/jcm-13-00021-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/74852834921b/jcm-13-00021-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/805c0646b149/jcm-13-00021-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/1009bc1ed091/jcm-13-00021-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723d/10779348/7ce2d821adb3/jcm-13-00021-g005.jpg

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Novel fibro-inflammatory biomarkers associated with disease activity in patients with Crohn's disease.新型成纤维细胞-炎症生物标志物与克罗恩病患者的疾病活动相关。
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Positioning and Usefulness of Biomarkers in Inflammatory Bowel Disease.
血清胶原蛋白生物标志物反映了与溃疡性结肠炎活动及对乌司奴单抗治疗反应相关的组织特异性成纤维细胞。
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