Serum Glycoproteome Profiles for Distinguishing Intestinal Fibrosis from Inflammation in Crohn's Disease.
Serum Glycoproteome Profiles for Distinguishing Intestinal Fibrosis from Inflammation in Crohn's Disease.
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血清糖蛋白酶特征，以区分肠纤维化与克罗恩病的炎症。
DOI：
10.1371/journal.pone.0170506
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Higgins PD
中科院分区：
文献类型：
--
作者：
Stidham RW;Wu J;Shi J;Lubman DM;Higgins PD
在克罗恩病（CD）引起的炎症共存的情况下，难以可靠地鉴定和定量肠纤维化。我们的目的是使用血清糖蛋白质组谱鉴定区分CD的炎性表型和纤维狭窄表型的血清生物标志物。作为一项三级医疗中心队列研究的一部分，通过定量血清糖蛋白组谱对纤维狭窄和炎症为主CD表型的受试者（每组n = 20）进行比较。凝集素洗脱后，糖蛋白进行液相色谱，然后串联质谱。还通过血清ELISA（一种广泛可用的技术）测量了鉴定的纤维化候选生物标志物。在≥80%的受试者中，5种糖蛋白的相对丰度变化≥20%，包括软骨寡聚基质蛋白（COMP）和肝细胞生长因子激活剂（HGFA）。使用ELISA，纤维狭窄组与炎性CD组的COMP（431.7±112.7 vs. 348.7±90.5 ng/mL，p = 0.012）和HGFA（152.7±66.5 vs. 107.1±38.7 ng/mL，p = 0.031）血清水平升高。在纤维狭窄组中，候选生物标志物的个体内变化显示，在切除所有患病肠后，HGFA水平显著下降（152.7±66.5 vs. 107.1±38.7 ng/mL，p = 0.015）; COMP水平不变。免疫组化染色证实COMP存在于切除的纤维狭窄组织的粘膜下层和肌层中。在这项生物标志物发现研究中，几种血清糖蛋白，特别是COMP和HGFA，在主要炎性和纤维狭窄CD表型之间存在差异。基于血液的纤维化生物标志物的开发将为IBD的现有预后工具提供重要补充，有助于决定治疗强度和机制选择，手术和监测CD的未来抗纤维化治疗。
Reliable identification and quantitation of intestinal fibrosis in the setting of co-existing inflammation due to Crohn’s disease (CD) is difficult. We aimed to identify serum biomarkers which distinguish inflammatory from fibrostenotic phenotypes of CD using serum glycoproteome profiles. Subjects with fibrostenotic and inflammation-predominant CD phenotypes (n = 20 per group) underwent comparison by quantitative serum glycoproteome profiles as part of a single tertiary care center cohort study. Following lectin elution, glycoproteins underwent liquid chromatography followed by tandem mass spectrometry. Identified candidate biomarkers of fibrosis were also measured by serum ELISA, a widely available technique. Five (5) glycoproteins demonstrated a ≥20% relative abundance change in ≥80% of subjects, including cartilage oligomeric matrix protein (COMP) and hepatocyte growth factor activator (HGFA). COMP (431.7±112.7 vs. 348.7±90.5 ng/mL, p = 0.012) and HGFA (152.7±66.5 vs. 107.1±38.7 ng/mL, p = 0.031) serum levels were elevated in the fibrostenotic vs. inflammatory CD groups using ELISA. Within the fibrostenotic group, intra-individual changes of candidate biomarkers revealed HGFA levels significantly declined following the resection of all diseased intestine (152.7±66.5 vs. 107.1±38.7 ng/mL, p = 0.015); COMP levels were unchanged. Immunohistochemical staining confirmed the presence of COMP in the submucosa and muscularis of resected fibrostenotic tissue. In this biomarker discovery study, several serum glycoproteins, specifically COMP and HGFA, differ between between predominately inflammatory and fibrostenotic CD phenotypes. The development of blood-based biomarkers of fibrosis would provide an important complement to existing prognostic tools in IBD, aiding decisions on therapeutic intensity and mechanism selection, surgery, and the monitoring of future anti-fibrotic therapies for CD.