Intestinal Research

Original Articles

Inflammatory Bowel Diseases

Prospective validation of CD4⁺CD25⁺FOXP3⁺ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn’s disease: Ritika Rampal, Saurabh Kedia, Mohamad Nahidul Wari, Deepak Madhu, Amit Kumar Singh, Veena Tiwari, V. Pratap Mouli, Srikant Mohta, Govind Makharia, Vineet Ahuja; Intest Res 2021;19(2):232-238. Published online May 8, 2020; DOI: https://doi.org/10.5217/ir.2019.09181

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 naïve 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.

Citations

Citations to this article as recorded by

FoxP3-positive T regulatory cells and its effector mechanisms in Crohn’s disease: an immunohistochemical and image morphometric analysis on endoscopic mucosal biopsies
Susama Patra, Shalini Chaudhary, Subash Chandra Samal, Pavithra Ayyanar, Somanath Padhi, Hemanta Kumar Nayak, Amit Kumar Satapathy, Saurav Nayak, Ajit Sahu, Tapaskanti Parida, Mohammed Shahin
European Journal of Gastroenterology & Hepatology.2025; 37(7): 799. CrossRef
New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis
Himanshu Narang, Saurabh Kedia, Vineet Ahuja
Current Opinion in Infectious Diseases.2024; 37(5): 392. CrossRef
Evidence-based approach to diagnosis and management of abdominal tuberculosis
Daya Krishna Jha, Mythili Menon Pathiyil, Vishal Sharma
Indian Journal of Gastroenterology.2023; 42(1): 17. CrossRef
Gut Microbiome in Probable Intestinal Tuberculosis and Changes following Anti-Tuberculosis Treatment
Hyuk Yoon, Young Soo Park, Cheol Min Shin, Nayoung Kim, Dong Ho Lee
Yonsei Medical Journal.2022; 63(1): 34. CrossRef
Single-nucleotide polymorphisms and activities of indoleamine 2,3-dioxygenase isoforms, IDO1 and IDO2, in tuberculosis patients
Tingming Cao, Guangming Dai, Hongqian Chu, Chengcheng Kong, Huijuan Duan, Na Tian, Zhaogang Sun
Hereditas.2022;[Epub] CrossRef
Recent advances in the diagnosis of intestinal tuberculosis
Hasan Maulahela, Marcellus Simadibrata, Erni Juwita Nelwan, Nur Rahadiani, Editha Renesteen, S. W. T. Suwarti, Yunita Windi Anggraini
BMC Gastroenterology.2022;[Epub] CrossRef
Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis
Saurabh Kedia, Raju Sharma, Sudheer Kumar Vuyyuru, Deepak Madhu, Pabitra Sahu, Bhaskar Kante, Prasenjit Das, Ankur Goyal, Karan Madan, Govind Makharia, Vineet Ahuja
Intestinal Research.2022; 20(2): 184. CrossRef
Inflammatory bowel disease in Korea: epidemiology and pathophysiology
Jung Won Lee, Chang Soo Eun
The Korean Journal of Internal Medicine.2022; 37(5): 885. CrossRef
Intestinal tuberculosis or Crohn's disease: Illusion or delusion or allusion
Saurabh Kedia, Vineet Ahuja
JGH Open.2021; 5(2): 177. CrossRef
Deep‐learning system for real‐time differentiation between Crohn's disease, intestinal Behçet's disease, and intestinal tuberculosis
Jung Min Kim, Jun Gu Kang, Sungwon Kim, Jae Hee Cheon
Journal of Gastroenterology and Hepatology.2021; 36(8): 2141. CrossRef
Mycobacterium tuberculosis (MTB) antigen-induced upregulation of interleukin-35 expression in patients with MTB infection: In vitro blockade of the effects of interleukin-35 on T lymphocyte subsets
Hongbin Jiang, Beinian Cui, Jun Zhang
Pathogens and Disease.2021;[Epub] CrossRef

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IBD

Selective M1 macrophage polarization in granuloma-positive and granuloma-negative Crohn's disease, in comparison to intestinal tuberculosis: Prasenjit Das, Ritika Rampal, Sonakshi Udinia, Tarun Kumar, Sucharita Pilli, Nahid Wari, Imtiaz Khan Ahmed, Saurabh Kedia, Siddhartha Datta Gupta, Dhiraj Kumar, Vineet Ahuja; Intest Res 2018;16(3):426-435. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.426

Abstract PDF PubReader ePub

<b>Background/Aims</b><br/>

Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB).

Methods

Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1_φ marker) and CD163/CD68 (an M2_φ marker), and the ratio of M1_φ to M2_φ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment.

Results

M1_φ polarization was more prominent in CD biopsies (P=0.002) than in iTB (P=0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1_φ predominance was significant (P=0.001). In iTB, the densities of M1_φ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1_φ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients.

Conclusions

Proinflammatory M1_φ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD.

Citations

Citations to this article as recorded by

Macrophage polarization: an important role in inflammatory diseases
Min Luo, Fukun Zhao, Huan Cheng, Mu Su, Yuanmin Wang
Frontiers in Immunology.2024;[Epub] CrossRef
The gut barrier as a gatekeeper in colorectal cancer treatment
Roy Hajjar, Carole Richard, Manuela M. Santos
Oncotarget.2024; 15(1): 562. CrossRef
New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis
Himanshu Narang, Saurabh Kedia, Vineet Ahuja
Current Opinion in Infectious Diseases.2024; 37(5): 392. CrossRef
Differentiating gastrointestinal tuberculosis and Crohn's disease- a comprehensive review
Arup Choudhury, Jasdeep Dhillon, Aravind Sekar, Pankaj Gupta, Harjeet Singh, Vishal Sharma
BMC Gastroenterology.2023;[Epub] CrossRef
Clinical Usefulness of Immune Profiling for Differential Diagnosis between Crohn’s Disease, Intestinal Tuberculosis, and Behcet’s Disease
Ji Won Yoo, Su In Jo, Dong Woo Shin, Ji Won Park, Sung-Eun Kim, Hyun Lim, Ho Suk Kang, Sung-Hoon Moon, Min Kyu Kim, Sang-Yeob Kim, Sung Wook Hwang, Jae Seung Soh
Diagnostics.2023; 13(18): 2904. CrossRef
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Journal of Veterinary Diagnostic Investigation.2022; 34(1): 68. CrossRef
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Communications Biology.2022;[Epub] CrossRef
Lacticaseibacillus casei Strain Shirota Modulates Macrophage-Intestinal Epithelial Cell Co-Culture Barrier Integrity, Bacterial Sensing and Inflammatory Cytokines
Andrew Foey, Neama Habil, Alex Strachan, Jane Beal
Microorganisms.2022; 10(10): 2087. CrossRef
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Haiyuan Xing, Ruiyan Li, Yun'an Qing, Boda Ying, Yanguo Qin
Applied Materials Today.2021; 22: 100969. CrossRef
Two ST11 Klebsiella pneumoniae strains exacerbate colorectal tumorigenesis in a colitis-associated mouse model
Ming-Ko Chiang, Pei-Yi Hsiao, Yen-Yi Liu, Hui-Ling Tang, Chien-Shun Chiou, Min-Chi Lu, Yi-Chyi Lai
Gut Microbes.2021;[Epub] CrossRef
A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
Susree Roy, Suchandrima Ghosh, Mallica Banerjee, Sayantan Laha, Dipanjan Bhattacharjee, Rajib Sarkar, Sujay Ray, Arko Banerjee, Ranajoy Ghosh, Aniket Halder, Alakendu Ghosh, Raghunath Chatterjee, Simanti Datta, Gopal Krishna Dhali, Soma Banerjee
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Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization
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Understanding Pathogenesis and Care Challenges of Immune Reconstitution Inflammatory Syndrome in Fungal Infections
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14,515 View
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14 Web of Science
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