Association Between Plasma Level of Collagen Type III Alpha 1 Chain and Development of Strictures in Pediatric Patients With Crohn's Disease.
Association Between Plasma Level of Collagen Type III Alpha 1 Chain and Development of Strictures in Pediatric Patients With Crohn's Disease.
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DOI：
10.1016/j.cgh.2018.09.008
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发表时间：
2019-08
期刊：
影响因子：
--
通讯作者：
Kugathasan S
中科院分区：
文献类型：
--
作者：
Ballengee CR;Stidham RW;Liu C;Kim MO;Prince J;Mondal K;Baldassano R;Dubinsky M;Markowitz J;Leleiko N;Hyams J;Denson L;Kugathasan S
有几个血清生物标志物，以确定克罗恩病（CD）患者的狭窄发展的风险。细胞外基质成分III型胶原α 1链（COL 3A 1）和软骨寡聚基质蛋白（COMP）可能有助于肠纤维化。我们调查了患有炎症性CD（B1）的儿童在诊断时是否会增加COL 3A 1或COMP的血浆水平，与保持B1的儿童相比。我们将结果与先前研究的生物标志物进行了比较，包括针对集落刺激因子2（CSF 2）的自身抗体。我们从2008年至2012年在美国和加拿大的28个地点完成的克罗恩病儿童快速疾病进展的免疫原性和微生物标志物的风险分层和鉴定中选择了161名受试者（平均年龄12.2岁; 62%男性）。这些儿童在诊断时接受结肠镜检查和上消化道内镜检查，每6个月随访一次，持续36个月;在基线时收集血浆样本。根据CD表型，将儿童分为第1组（诊断和随访时的B1表型）、第2组（诊断时的B2表型）或第3组（诊断时的B1表型，在随访期间发生狭窄）。从患者和40名基线时没有炎症性肠病的儿童（对照组）中收集血浆样本，并通过ELISA分析以测量COL 3A 1和COMP。这些结果与先前生物标志物研究的结果进行比较。采用Kruskal-Wallis检验和Bonferroni校正的成对Dunn检验比较组间差异。第3组血浆中COL 3A 1的基线浓度中位数显著高于第1组（P<0.01）和对照组（P= 0.01）。COMP的中位基线血浆浓度在组间无显著差异。包括COL 3A 1和抗CSF 2的基线浓度的模型鉴定了B2 vs B1 CD患者，曲线下面积为0.80（95%可信区间，0.71-0.89）;合并浓度识别狭窄患者的灵敏度值为0.70（95% CI，0.55-0.83），特异性值为0.83（95% CI 0.67-0.93）。我们发现，在诊断时通过ELISA测量的COL 3A 1的中位血浆浓度在后来发展为狭窄的CD患者中显著高于无狭窄的患者。COL 3A 1和抗CSF 2的浓度组合可用于识别CD诊断时有未来狭窄风险的儿科患者。
There are few serum biomarkers to identify patients with Crohn’s disease (CD) who are at risk for stricture development. The extracellular matrix components, collagen type III alpha 1 chain (COL3A1) and cartilage oligomeric matrix protein (COMP), could contribute to intestinal fibrosis. We investigated whether children with inflammatory CD (B1) who later develop strictures (B2) have increased plasma levels of COL3A1 or COMP at diagnosis, compared to children who remain B1. We compared results to previously studied biomarkers, including autoantibodies against colony stimulating factor 2 (CSF2). We selected 161 subjects (mean age, 12.2 years; 62% male) from the Risk Stratification and Identification of Immunogenic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s cohort, completed at 28 sites in the United States and Canada from 2008 through 2012. The children underwent colonoscopy and upper endoscopy at diagnosis and were followed every 6 months for 36 months; plasma samples were collected at baseline. Based on CD phenotype, children were separated to group 1 (B1 phenotype at diagnosis and follow up), group 2 (B2 phenotype at diagnosis), or group 3 (B1 phenotype at diagnosis who developed strictures during follow up). Plasma samples were collected from patients and 40 children without inflammatory bowel disease (controls) at baseline and analyzed by ELISA to measure COL3A1 and COMP. These results were compared with those from a previous biomarker study. Kruskal-Wallis test and pairwise Dunn’s tests with Bonferroni correction were used to compare differences among groups. The median baseline concentration of COL3A1 was significantly higher in plasma from group 3 vs group 1 (P<.01) and controls (P=.01). Median baseline plasma concentrations of COMP did not differ significantly among groups. A model comprising baseline concentrations of COL3A1 and anti-CSF2 identified patients with B2 vs B1 CD with an area under the curve of 0.80 (95% CI, 0.71–0.89); the combined concentration identified patients with strictures with a sensitivity value of 0.70 (95% CI, 0.55–0.83) and a specificity value of 0.83 (95% CI 0.67–0.93). We found median plasma concentrations of COL3A1, measured by ELISA at diagnosis, to be significantly higher in patients with CD who later developed strictures than in patients without strictures. The combination of concentrations of COL3A1 and anti-CSF2 might be used to identify pediatric patients at CD diagnosis who are at risk for future strictures.
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影响因子：
4.9
作者：
Gathungu G;Kim MO;Ferguson JP;Sharma Y;Zhang W;Ng SM;Bonkowski E;Ning K;Simms LA;Croft AR;Stempak JM;Walker N;Huang N;Xiao Y;Silverberg MS;Trapnell B;Cho JH;Radford-Smith GL;Denson LA
通讯作者：
Denson LA
血清糖蛋白酶特征，以区分肠纤维化与克罗恩病的炎症。
影响因子：
3.7
作者：
Stidham RW;Wu J;Shi J;Lubman DM;Higgins PD
通讯作者：
Higgins PD
影响因子：
29.4
作者：
Han X;Uchida K;Jurickova I;Koch D;Willson T;Samson C;Bonkowski E;Trauernicht A;Kim MO;Tomer G;Dubinsky M;Plevy S;Kugathsan S;Trapnell BC;Denson LA
通讯作者：
Denson LA
影响因子：
9
作者：
Alvarez-Lobos, M;Arostegui, JI;Panés, J
通讯作者：
Panés, J
影响因子：
24.5
作者：
Satsangi, J.;Silverberg, M. S.;Colombel, J-F
通讯作者：
Colombel, J-F