Prospective validation of CD4+CD25+FOXP3+ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn's disease
Open Access
- 1 April 2021
- journal article
- research article
- Published by Korean Association for the Study of Intestinal Diseases in Intestinal Research
- Vol. 19 (2), 232-238
- https://doi.org/10.5217/ir.2019.09181
Abstract
Background/Aims: Crohn's disease (CD) and intestinal tuberculosis (ITB) remain "difficult-to-differentiate" diseases. We have previously documented peripheral blood frequency of CD4(+)CD25(+)FOXP3(+) T-regulatory cells (Treg) as a biomarker to differentiate CD and ITB. We tried to validate these results in a larger cohort of CD and ITB patients. Methods: Seventy treatment naive patients of CD (n= 23) and ITB (n= 47) (diagnosed by standard criteria) were recruited prospectively from October 2016 to May 2017. Patients with history of antitubercular therapy in the past were excluded. The frequency of Treg cells in peripheral blood was determined by flow cytometry, and compared between CD and ITB patients. Results: Similar to our previous study, frequency of Treg cells in peripheral blood was significantly increased in ITB as compared to CD patients (40.9 [interquartile range, 33- 50] vs. 24.9 [interquartile range, 14.4-29.6], P< 0.001). Further, the receiver operating characteristics curve also showed good diagnostic accuracy with an area under the curve (AUC) of 0.77 (95% confidence interval, 0.65-0.89) and a FOXP3(+) cutoff value of > 31.3% had a sensitivity and specificity of 83% and 82.6% respectively, to differentiate ITB from CD. Even for the indeterminate cases (n= 33), Treg cell frequency had similar diagnostic accuracy with an AUC of 0.85 (95% confidence interval, 0.68-0.95) and a cutoff of 32.37% had sensitivity and specificity of 87% and 95% respectively, to differentiate ITB from CD. Conclusions: The current findings validate that the increased frequency of CD4(+)CD25(+)FOXP3(+) Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD.Funding Information
- Indian Council of Medical Research
This publication has 29 references indexed in Scilit:
- Asia Pacific Consensus Statements on Crohn's disease. Part 1: Definition, diagnosis, and epidemiologyJournal of Gastroenterology and Hepatology, 2015
- Systematic review with meta‐analysis: Accuracy of interferon‐gamma releasing assay and anti‐Saccharomyces cerevisiae antibody in differentiating intestinal tuberculosis from Crohn's disease in AsiansJournal of Gastroenterology and Hepatology, 2014
- Expression of CD4+ forkhead box P3 (FOXP3)+ regulatory T cells in inflammatory bowel diseaseJournal of Digestive Diseases, 2011
- T regulatory cells and Th1/Th2 cytokines in peripheral blood from tuberculosis patientsEuropean Journal of Clinical Microbiology & Infectious Diseases, 2010
- Foxp3+ Regulatory T Cells, Th17 Effector Cells, and Cytokine Environment in Inflammatory Bowel DiseaseJournal of Clinical Immunology, 2009
- FoxP3+ Regulatory T Cells Suppress Effector T-Cell Function at Pathologic Site in Miliary TuberculosisAmerican Journal of Respiratory and Critical Care Medicine, 2009
- Crohn’s Disease in India: A Multicenter Study from a Country Where Tuberculosis Is EndemicDigestive Diseases and Sciences, 2008
- Anti-Saccharomyces cerevisiae Antibody Does Not Differentiate Between Crohn's Disease and Intestinal TuberculosisDigestive Diseases and Sciences, 2006
- Analysis of Colonoscopic Findings in the Differential Diagnosis Between Intestinal Tuberculosis and Crohn’s DiseaseEndoscopy, 2006
- Segmental colonoscopic biopsies in the differentiation of ileocolic tuberculosis from Crohn's diseaseJournal of Gastroenterology and Hepatology, 2005