可溶性 syndecan-1 作为肠道炎症标志物：一种新型生物标志物联合检测用于非侵入性预测活动期溃疡性结肠炎的初步研究和评估。

Soluble syndecan-1 as marker of intestinal inflammation: A preliminary study and evaluation of a new panel of biomarkers for non-invasive prediction of active ulcerative colitis.

机构信息

Department of Medicine 1, Klinikum Ibbenbüren, Germany.

Department of Medicine, Evangelisches Krankenhaus Weende, Göttingen, Germany.

出版信息

Adv Clin Exp Med. 2021 Jul;30(7):655-660. doi: 10.17219/acem/139040.

DOI:10.17219/acem/139040

PMID:34286513

Abstract

BACKGROUND

Syndecan-1 (Sdc1) is a heparin sulfate proteoglycan expressed in intestinal epithelium, which plays a crucial role in inflammation and epithelial repair. Sdc1-knockout mice have a deteriorated course of dextran sulfate sodium-induced colitis as compared to controls. Syndecan-1 is also shed into the serum during inflammation of the epithelium. We hypothesized that an increased serum level of soluble Sdc1 is a biomarker of intestinal inflammation in ulcerative colitis (UC).

OBJECTIVES

To evaluate serum soluble Sdc1 as a biomarker of intestinal inflammation in UC.

MATERIAL AND METHODS

This is a proof-of-concept study. Patients were recruited by the University Hospital Münster and HELIOS Albert Schweitzer Klinik Northeim (Germany). Blood samples were collected from UC patients actively suffering from this condition and those in remission. The levels of Sdc1 were measured with Diaclone CD 138 ELISA kit (Diaclone Research, Besançon, France) and routine clinical data were collected (C-reactive protein (CRP) levels, calprotectin in stool samples). Data were analyzed using SPSS software.

RESULTS

Soluble Sdc1 levels were significantly elevated in the active UC group as compared to the inactive UC group (94.5 ±68.1 ng/mL compared to 28.3 ±12.6 ng/mL, p = 0.0020). The levels of Sdc1 also significantly correlated with the severity of UC as measured with the Mayo score (p = 0.0248). Receiver operating characteristic (ROC) analysis showed a good correlation of Sdc1 with an endoscopic Mayo score ≥2, with a value of 0.7747 (95% confidence interval (95% CI) = 0.5775-0.9718). A cutoff value of 37.1 ng/mL of Sdc1 showed a sensitivity of 78% and a specificity of 77%. A panel of biomarkers including CRP, hemoglobin, hematocrit, and Sdc1 was able to precisely predict active UC with an area under the curve (AUC) = 0.9395 (95% CI = 0.8509-1.0000).

CONCLUSIONS

Serum soluble Sdc1 correlates significantly with mucosa inflammation and Mayo score in UC. Clinical trials No. NCT02333526.

摘要

背景

硫酸乙酰肝素蛋白聚糖-1（Sdc1）是一种在肠道上皮细胞中表达的肝素硫酸蛋白聚糖，在炎症和上皮修复中起着至关重要的作用。与对照组相比，Sdc1 敲除小鼠的葡聚糖硫酸钠诱导结肠炎病程恶化。Sdc1 也在上皮炎症期间被释放到血清中。我们假设血清可溶性 Sdc1 水平升高是溃疡性结肠炎（UC）肠道炎症的生物标志物。

目的

评估血清可溶性 Sdc1 作为 UC 肠道炎症的生物标志物。

材料和方法

这是一项概念验证研究。患者由明斯特大学医院和 HELIOS Albert Schweitzer Klinik Northeim（德国）招募。从患有活动性 UC 和缓解期 UC 的患者中采集血样。使用 Diaclone CD 138 ELISA 试剂盒（Diaclone Research，Besançon，法国）测量 Sdc1 水平，并收集常规临床数据（C 反应蛋白（CRP）水平、粪便样本中的钙卫蛋白）。使用 SPSS 软件进行数据分析。

结果

与缓解期 UC 组相比，活动期 UC 组的可溶性 Sdc1 水平显著升高（94.5±68.1ng/ml 比 28.3±12.6ng/ml，p=0.0020）。Sdc1 水平也与 Mayo 评分（p=0.0248）所测 UC 的严重程度显著相关。受试者工作特征（ROC）分析显示 Sdc1 与内镜 Mayo 评分≥2 具有良好的相关性，值为 0.7747（95%置信区间（95%CI）=0.5775-0.9718）。Sdc1 的截断值为 37.1ng/ml 时，敏感性为 78%，特异性为 77%。包括 CRP、血红蛋白、红细胞压积和 Sdc1 在内的生物标志物组能够以曲线下面积（AUC）=0.9395（95%CI=0.8509-1.0000）准确预测活动性 UC。