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外周血中 CD4+ CD25+ FOXP3+ T 细胞的频率是鉴别肠结核与克罗恩病的生物标志物。

CD4+ CD25+ FOXP3+ T cell frequency in the peripheral blood is a biomarker that distinguishes intestinal tuberculosis from Crohn's disease.

机构信息

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Department of HLA and Transplant Immunology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

PLoS One. 2018 Feb 28;13(2):e0193433. doi: 10.1371/journal.pone.0193433. eCollection 2018.

Abstract

BACKGROUND

Distinguishing between Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) has been a challenging task for clinicians due to their similar presentation. CD4+FOXP3+ T regulatory cells (Tregs) have been reported to be increased in patients with pulmonary tuberculosis. However, there is no such data available in ITB. The aim of this study was to investigate the differential expression of FOXP3+ T cells in patients with ITB and CD and its utility as a biomarker.

METHODS

The study prospectively recruited 124 patients with CD, ITB and controls: ulcerative colitis (UC) and patients with only haemorrhoidal bleed. Frequency of CD4+CD25+FOXP3+ Tregs in peripheral blood (flow cytometry), FOXP3 mRNA expression in blood and colonic mucosa (qPCR) and FOXP3+ T cells in colonic mucosa (immunohistochemistry) were compared between controls, CD and ITB patients.

RESULTS

Frequency of CD4+CD25+FOXP3+ Treg cells in peripheral blood was significantly increased in ITB as compared to CD. Similarly, significant increase in FOXP3+ T cells and FOXP3 mRNA expression was observed in colonic mucosa of ITB as compared to CD. ROC curve showed that a value of >32.5% for FOXP3+ cells in peripheral blood could differentiate between CD and ITB with a sensitivity of 75% and a specificity of 90.6%.

CONCLUSION

Phenotypic enumeration of peripheral CD4+CD25+FOXP3+ Treg cells can be used as a non-invasive biomarker in clinics with a high diagnostic accuracy to differentiate between ITB and CD in regions where TB is endemic.

摘要

背景

由于临床表现相似,克罗恩病 (CD) 和肠结核 (ITB) 的鉴别一直是临床医生面临的挑战。已有报道称,肺结核患者的 CD4+FOXP3+调节性 T 细胞 (Treg) 增加。然而,在 ITB 中没有这样的数据。本研究旨在探讨 ITB 和 CD 患者中 FOXP3+T 细胞的差异表达及其作为生物标志物的应用。

方法

本研究前瞻性招募了 124 例 CD、ITB 和对照患者:溃疡性结肠炎 (UC) 和仅伴痔出血的患者。比较了外周血 (流式细胞术) 中 CD4+CD25+FOXP3+Treg 的频率、血和结肠黏膜中 FOXP3 mRNA 表达 (qPCR) 以及结肠黏膜中 FOXP3+T 细胞 (免疫组化) 在对照组、CD 和 ITB 患者之间的差异。

结果

与 CD 相比,ITB 患者外周血中 CD4+CD25+FOXP3+Treg 细胞的频率显著增加。同样,ITB 患者结肠黏膜中 FOXP3+T 细胞和 FOXP3 mRNA 表达也显著增加。ROC 曲线显示,外周血中 FOXP3+细胞>32.5%可区分 CD 和 ITB,敏感性为 75%,特异性为 90.6%。

结论

外周血 CD4+CD25+FOXP3+Treg 细胞的表型计数可作为一种非侵入性生物标志物,用于在结核病流行地区具有较高诊断准确性的临床中,区分 ITB 和 CD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be03/5830992/d409852f1577/pone.0193433.g001.jpg

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