Novel serological neo-epitope markers of extracellular matrix proteins for the detection of portal hypertension.
Novel serological neo-epitope markers of extracellular matrix proteins for the detection of portal hypertension.
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DOI：
10.1111/apt.12484
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发表时间：
2013-11
影响因子：
7.6
通讯作者：
Krag A
中科院分区：
文献类型：
--
作者：
Leeming DJ;Karsdal MA;Byrjalsen I;Bendtsen F;Trebicka J;Nielsen MJ;Christiansen C;Møller S;Krag A
背景肝静脉压力梯度（HVPG）是肝硬化门脉高压（PHT）的一种侵入性但重要的诊断和预后标志物。在肝硬化期间，基质金属蛋白酶（MMP）对纤维化组织的重塑是一个永久过程，产生被称为新表位的降解细胞外基质（ECM）蛋白的小片段，然后释放到循环中。目的 研究它们作为血浆标记物检测 PHT 的潜力。方法纳入94例酒精性肝硬化患者和20例肝脏健康对照者。收集患者的临床和实验室数据。所有患者均接受抽血测量 HVPG。在这些样品中，测量了以下降解或形成标记物：C1M（I 型胶原）、C3M 和 PRO-C3（III 型胶原）、C4M 和 P4NP 7S（IV 型胶原）、C5M（V 型胶原）、C6M（VI 型胶原）、BGM（双糖链蛋白聚糖）、ELM（弹性蛋白）、CRPM (CRP)。结果除 CRPM 外，所有 ECM 标志物均与 HVPG 显着相关。有趣的是，HVPG >10 mmHg 的患者中 C4M、C5M 和 ELM 水平显着较高。多元回归分析确定 PRO-C3、C6M 和 ELM 是重要的决定因素，而模型 A 和 B（包括 PRO-C3、ELM、C6M 和终末期肝病模型 (MELD)）更好地描述了 PHT（r = 0.75，P < 0.0001）。该模型为具有临床意义的 PHT 提供了 >100 的比值比。结论这些新型非侵入性细胞外基质标志物反映了肝功能障碍的程度。不同程度的门脉高压与这些循环新表位相关。使用单一血液样本，这些新表位与 MELD 结合检测门脉高压水平。
BackgroundThe hepatic venous pressure gradient (HVPG) is an invasive, but important diagnostic and prognostic marker in cirrhosis with portal hypertension (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process generating small fragments of degraded extracellular matrix (ECM) proteins known as neoepitopes, which are then released into the circulation. AimTo investigate their potential as plasma markers for detection of PHT. MethodsNinety-four patients with alcoholic cirrhosis and 20 liver-healthy controls were included. Clinical and laboratory data of the patients were collected. All patients received HVPG measurement with blood sampling. In these samples, the following degradation or formation markers were measured: C1M (type I-collagen), C3M and PRO-C3 (type III collagen), C4M and P4NP 7S (type IV collagen), C5M (type V collagen), C6M (type VI collagen), BGM (biglycan), ELM (elastin), CRPM (CRP). ResultsAll ECM markers except for CRPM correlated significantly with HVPG. Interestingly, C4M, C5M and ELM levels were significantly higher in patients with HVPG >10 mmHg. Multiple regression analysis identified PRO-C3, C6M and ELM as significant determinants, while the models A and B including PRO-C3, ELM, C6M and model for end-stage liver disease (MELD) provided better description of PHT (r = 0.75, P < 0.0001). The models provided odds ratios of >100 for having clinical significant PHT. ConclusionsThese novel non-invasive extracellular matrix markers reflect the degree of liver dysfunction. The different degrees of portal hypertension correlated with these circulating neoepitopes. Using a single blood sample, these neoepitopes in combination with MELD detect the level of portal hypertension.
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影响因子：
2.4
作者：
Baranova A;Lal P;Birerdinc A;Younossi ZM
通讯作者：
Younossi ZM
影响因子：
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作者：
Leeming, Diana J.;Nielsen, Mette J.;Karsdal, Morten A.
通讯作者：
Karsdal, Morten A.
影响因子：
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作者：
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通讯作者：
Bosch, Jaime
影响因子：
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作者：
BENTSEN, KD;HENRIKSEN, JH;LORENZEN, I
通讯作者：
LORENZEN, I
影响因子：
5
作者：
GRESSNER, AM;TITTOR, W;PICKKOBER, KH
通讯作者：
PICKKOBER, KH