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溃疡性结肠炎患者的全身炎症反应与艰难梭菌感染。

Systemic Inflammatory Responses in Ulcerative Colitis Patients and Clostridium difficile Infection.

机构信息

Division of Gastroenterology, Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.

Internal Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Dig Dis Sci. 2018 Jul;63(7):1801-1810. doi: 10.1007/s10620-018-5044-1. Epub 2018 Apr 12.

Abstract

BACKGROUND/AIMS: Finding differences in systemic inflammatory response in ulcerative colitis (UC), UC with Clostridium difficile infection (CDI), and CDI could lead to a better ability to differentiate between UC with symptomatic CDI and UC with C. difficile colonization, and could identify specific inflammatory pathways for UC or CDI, which could be therapeutic targets.

METHODS

We prospectively collected sera from symptomatic UC patients whose stools were tested for toxigenic C. difficile, and from CDI patients who did not have UC (CDI-noUC). The UC patients with positive tests (UC-CDI) were further categorized into responders to CDI treatment (UC-CDI-R) and non-responders (UC-CDI-NR). We compared serum inflammatory mediators among groups using unadjusted and adjusted multivariable statistics.

RESULTS

We included 117 UC [27 UC-CDI, 90 UC without CDI (UC-noCDI)] and 16 CDI-noUC patients. Principal component analysis (PCA) did not reveal significant differences either between UC-CDI and UC-noCDI groups, or between UC-CDI-R and UC-CDI-NR groups. In contrast, the PCA showed significant separation between the UC and CDI-noUC groups (P = 0.002). In these two groups, hepatocyte growth factor (HGF) and chemokine (C-C motif) ligand 2 (CCL2) levels were significantly lower and IL-23 levels were higher in UC patients in multivariable analyses. The model to distinguish UC from CDI including IL-23, HGF, CCL2, age, gender, and HGB had an AuROC of 0.93.

CONCLUSION

Inflammatory profiles could not distinguish UC-CDI from UC-noCDI, and UC-CDI-R from UC-CDI-NR. However, the UC and CDI-noUC groups were significantly different. Future work should examine whether therapeutic agents inhibiting IL-23 or stimulating HGF can treat UC.

摘要

背景/目的:在溃疡性结肠炎(UC)、合并艰难梭菌感染(CDI)的 UC 和 CDI 患者中寻找系统性炎症反应的差异,可能有助于更好地区分有症状 CDI 的 UC 与 UC 中艰难梭菌定植,并且能够确定 UC 或 CDI 的特定炎症途径,这些途径可能是治疗靶点。

方法

我们前瞻性地收集了有症状 UC 患者的血清,这些患者的粪便进行了产毒艰难梭菌检测,以及没有 UC 的 CDI 患者(CDI-noUC)。阳性检测的 UC 患者(UC-CDI)进一步分为对 CDI 治疗有反应的患者(UC-CDI-R)和无反应的患者(UC-CDI-NR)。我们使用未调整和调整后的多变量统计方法比较了各组血清炎症介质。

结果

我们纳入了 117 例 UC [27 例 UC-CDI,90 例 UC 无 CDI(UC-noCDI)]和 16 例 CDI-noUC 患者。主成分分析(PCA)既没有显示 UC-CDI 与 UC-noCDI 组之间,也没有显示 UC-CDI-R 与 UC-CDI-NR 组之间有显著差异。相比之下,PCA 显示 UC 组和 CDI-noUC 组之间有显著分离(P=0.002)。在这两组中,多变量分析显示,UC 患者的肝细胞生长因子(HGF)和趋化因子(C-C 基元)配体 2(CCL2)水平显著降低,IL-23 水平升高。包括 IL-23、HGF、CCL2、年龄、性别和 HGB 在内的区分 UC 和 CDI 的模型具有 0.93 的 AuROC。

结论

炎症谱不能区分 UC-CDI 与 UC-noCDI,也不能区分 UC-CDI-R 与 UC-CDI-NR。然而,UC 组和 CDI-noUC 组有显著差异。未来的研究应该检查抑制 IL-23 或刺激 HGF 的治疗药物是否可以治疗 UC。

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