Stidham Ryan W, Wu Jing, Shi Jiaqi, Lubman David M, Higgins Peter D R
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, United States of America.
Department of Surgery, University of Michigan Health System, Ann Arbor, MI, United States of America.
PLoS One. 2017 Jan 23;12(1):e0170506. doi: 10.1371/journal.pone.0170506. eCollection 2017.
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.
在克罗恩病（CD）并存炎症的情况下，可靠地识别和定量肠道纤维化具有难度。我们旨在利用血清糖蛋白组图谱鉴定区分CD炎症性与纤维狭窄性表型的血清生物标志物。
作为一项单一三级医疗中心队列研究的一部分，对具有纤维狭窄性和炎症为主型CD表型的受试者（每组n = 20）进行定量血清糖蛋白组图谱比较。在凝集素洗脱后，糖蛋白先进行液相色谱分析，然后进行串联质谱分析。通过血清ELISA（一种广泛应用的技术）对鉴定出的纤维化候选生物标志物进行检测。
五种糖蛋白在≥80%的受试者中显示出≥20%的相对丰度变化，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检测发现，纤维狭窄性CD组与炎症性CD组相比，COMP（431.7±112.7对348.7±90.5 ng/mL，p = 0.012）和HGFA（152.7±66.5对107.1±38.7 ng/mL，p = 0.031）的血清水平升高。在纤维狭窄性组内，候选生物标志物的个体内变化显示，切除所有病变肠段后HGFA水平显著下降（152.7±66.5对107.1±38.7 ng/mL，p = 0.015）；COMP水平未改变。免疫组织化学染色证实COMP存在于切除的纤维狭窄性组织的黏膜下层和肌层。
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，在主要为炎症性和纤维狭窄性CD表型之间存在差异。纤维化血液生物标志物的开发将为IBD现有的预后工具提供重要补充，有助于在治疗强度和机制选择、手术以及未来CD抗纤维化治疗监测方面做出决策。
