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Patra S, Chaudhary S, Samal SC, Ayyanar P, Padhi S, Nayak HK, Satapathy AK, Nayak S, Sahu A, Parida T, Shahin M. FoxP3-positive T regulatory cells and its effector mechanisms in Crohn's disease: an immunohistochemical and image morphometric analysis on endoscopic mucosal biopsies. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00509. [PMID: 40207496 DOI: 10.1097/meg.0000000000002971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
OBJECTIVE Crohn's disease (CD) is an immune inflammatory disorder of the gastrointestinal tract arising from a complex interplay of genetic, environmental, microbiome, and immune factors. Regulatory T cells (Tregs), characterized by FoxP3 expression, are crucial for maintaining immune homeostasis through PD-1/PD-L1 interaction, interleukin (IL)-10 release, and granzyme (GrB) production. This study aimed to elucidate the role of FoxP3 positive (+) Tregs in CD. METHODS Segmental colonoscopic biopsies from 46 treatment-naive CD cases (34 adults and 12 children) categorized into noninflamed [n = 32; Nancy histologic index (NHI) 0, 1] and inflamed (n = 100; NHI 2-4) mucosae using NHI. CD4, FoxP3, PD-1, IL-10, and GrB immunoexpression were analyzed by eyeballing and image morphometry. Findings were correlated with activity, granulomas, and skip lesions; and compared with site-matched non-inflammatory bowel disease (IBD) controls (n = 30). RESULTS FoxP3+ Tregs, IL-10, PD-1, and GrB expressions were significantly higher in NHI 3-4 mucosae than in NHI 0-1 and controls (P < 0.05). No significant differences were observed between adults and children, whereas those with granulomas had increased expression (P = 0.045). The FoxP3 : CD4 ratio positively correlated with IL-10 (Spearman, r = 0.307, P = 0.002), GrB (r = 0.302, P = 0.002), but not with PD-1 (r = 0.98, P = 0.33). CONCLUSIONS Our findings point to the possibility of a qualitative defect in FoxP3+ Tregs in CD. The functional arms of Tregs in CD need to be elucidated further in larger prospective cohorts to validate our observations and pave the way for future immunotherapy.
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Affiliation(s)
| | | | | | | | | | | | | | - Saurav Nayak
- Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Ajit Sahu
- Department of Pathology and Laboratory Medicine
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Narang H, Kedia S, Ahuja V. New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis. Curr Opin Infect Dis 2024; 37:392-401. [PMID: 39110076 DOI: 10.1097/qco.0000000000001054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Abstract
PURPOSE OF REVIEW Despite advances in our radiological, histological and microbiological armamentarium, distinguishing between Crohn's disease (CD) and intestinal tuberculosis (ITB), especially in a TB endemic country, continues to be a challenging exercise in a significant number of patients. This review aims to summarize current available evidence on novel diagnostic techniques which have a potential to fill the gap in our knowledge of differentiating between ITB and CD. RECENT FINDINGS Both ITB and CD are associated with altered host immune responses, and detection of these altered innate and adaptive immune cells has potential to distinguish ITB from CD. ITB and CD have different epigenetic, proteomic and metabolomic signatures, and recent research has focused on detecting these differences. In addition, the gut microbiome, which is involved in mucosal immunity and inflammatory responses, is considerably altered in both ITB and CD, and is another potential frontier, which can be tapped to discriminate between the two diseases. With technological advancements, we have newer radiological modalities including perfusion CT and dual-layer spectral detector CT enterography and evidence is emerging of their role in differentiating ITB from CD. Finally, time will tell whether the advent of artificial intelligence, with rapidly accumulating data in this field, will be the gamechanger in solving this puzzle of diagnostic dilemma between ITB and Crohn's disease. SUMMARY Recent advances need to be clinically validated before they can be used as novel diagnostic measures to differentiate Intestinal TB from CD.
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Affiliation(s)
- Himanshu Narang
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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Yannin Hernández-de la Cruz S, Ordaz-Robles T, Antonio Villaldama-Soriano M, Emmanuel Luna-Guzmán C, Almeida-Becerril T, Villa-Morales J, Cárdenas-Conejo A, Dolores Ruíz-Cruz E, Maldonado-Hernandez J, Bernabe-Garcia M, Barbosa-Cortés L, Rodríguez-Cruz M. The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy. Brain Dev 2024; 46:199-206. [PMID: 38388302 DOI: 10.1016/j.braindev.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 02/03/2024] [Accepted: 02/05/2024] [Indexed: 02/24/2024]
Abstract
BACKGROUND In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.
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Affiliation(s)
- Sthephanie Yannin Hernández-de la Cruz
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Thania Ordaz-Robles
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Marco Antonio Villaldama-Soriano
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Cristian Emmanuel Luna-Guzmán
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Tomas Almeida-Becerril
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Judith Villa-Morales
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Alan Cárdenas-Conejo
- Departamento de Genética Médica. Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, CDMX, Mexico.
| | - Eugenia Dolores Ruíz-Cruz
- Departamento de Genética, UMAE Hospital General "Dr. Gaudencio González Garza". Centro Médico Nacional "La Raza", IMSS, CDMX, México.
| | - Jorge Maldonado-Hernandez
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Mariela Bernabe-Garcia
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Lourdes Barbosa-Cortés
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
| | - Maricela Rodríguez-Cruz
- Laboratorio de Nutrición Molecular, Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México (CDMX), Mexico.
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Yoo JW, Jo SI, Shin DW, Park JW, Kim SE, Lim H, Kang HS, Moon SH, Kim MK, Kim SY, Hwang SW, Soh JS. Clinical Usefulness of Immune Profiling for Differential Diagnosis between Crohn's Disease, Intestinal Tuberculosis, and Behcet's Disease. Diagnostics (Basel) 2023; 13:2904. [PMID: 37761270 PMCID: PMC10529363 DOI: 10.3390/diagnostics13182904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/06/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
It is important to make a differential diagnosis between inflammatory diseases of the bowel with similar clinical and endoscopic features. The profiling of immune cells could be helpful for accurately diagnosing inflammatory bowel diseases. We compared immune marker expression between Crohn's disease (CD), intestinal Behcet's disease (BD), and intestinal tuberculosis (TB) and evaluated the usefulness of immune profiling in differentiating between these diseases. Biopsy specimens were acquired around ulcerations on the terminal ileum or cecum from five patients with each disease. Panel 1 included multiplex immunohistochemistry staining for CD8, CD4, Foxp3, CD20, programmed death-1, and granzyme B. CD56, CD68, CD163, CD11c, and HLA-DR were analyzed in panel 2. The differences in cytotoxic T cells (CD8+CD4-Fopx3-CD20-), helper T cells (CD8-CD4+Fopx3-CD20-), and regulatory T cells (CD8-CD4+Fopx3+CD20-) were also not significant. However, M1 macrophage (CD68+CD163-HLA-DR-) cell densities were significantly higher in intestinal BD than in other diseases. The expression level of dendritic cells (CD56-CD68-CD163-CD11c+HLA-DR+) was highest in intestinal TB and lowest in intestinal BD. The expression of immune cells, including M1 macrophages and dendritic cells, was different between CD, intestinal BD, and intestinal TB. Immune profiling can be helpful for establishing differential diagnoses of inflammatory bowel diseases.
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Affiliation(s)
- Ji Won Yoo
- Department of Internal Medicine, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89557, USA;
| | - Su In Jo
- PrismCDX Co., Ltd., Hwaseong-si 18469, Republic of Korea;
| | - Dong Woo Shin
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang 14068, Republic of Korea; (D.W.S.); (J.W.P.); (S.-E.K.); (H.L.); (H.S.K.); (S.-H.M.)
| | - Ji Won Park
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang 14068, Republic of Korea; (D.W.S.); (J.W.P.); (S.-E.K.); (H.L.); (H.S.K.); (S.-H.M.)
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang 14068, Republic of Korea; (D.W.S.); (J.W.P.); (S.-E.K.); (H.L.); (H.S.K.); (S.-H.M.)
| | - Hyun Lim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang 14068, Republic of Korea; (D.W.S.); (J.W.P.); (S.-E.K.); (H.L.); (H.S.K.); (S.-H.M.)
| | - Ho Suk Kang
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang 14068, Republic of Korea; (D.W.S.); (J.W.P.); (S.-E.K.); (H.L.); (H.S.K.); (S.-H.M.)
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang 14068, Republic of Korea; (D.W.S.); (J.W.P.); (S.-E.K.); (H.L.); (H.S.K.); (S.-H.M.)
| | - Min Kyu Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
| | - Sang-Yeob Kim
- Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea;
| | - Sung Wook Hwang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
| | - Jae Seung Soh
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, University of Hallym College of Medicine, Anyang 14068, Republic of Korea; (D.W.S.); (J.W.P.); (S.-E.K.); (H.L.); (H.S.K.); (S.-H.M.)
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Duan S, Cao Y, Chen P, Yang Y, Zhang Y. Circulating and intestinal regulatory T cells in inflammatory bowel disease: A systemic review and meta-analysis. Int Rev Immunol 2023; 43:83-94. [PMID: 37615427 DOI: 10.1080/08830185.2023.2249525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/17/2023] [Indexed: 08/25/2023]
Abstract
Regulatory T cells (Tregs) play an important immunosuppressive role in inflammatory bowel disease (IBD). However, findings on the quantitative and functional changes of intestinal and circulating Tregs in patients with IBD are rather contradictory. We therefore conducted a meta-analysis on this issue. The pooled effect was assessed using the standardized mean difference (SMD) with a 95% confidence interval (CI), and subgroup analyses were performed to investigate heterogeneity. This analysis included 764 IBD (402 UC and 362 CD) patients and 341 healthy controls (HCs) pooled from 17 eligible studies. The percentage of circulating Tregs was significantly decreased in active IBD patients compared to HCs (SMD = -0.95, p < 0.001) and inactive IBD patients (SMD = -0.80, p < 0.001). There was no difference in the percentage of circulating Tregs between inactive IBD patients and HCs. The suppressive function of circulating Tregs was impaired in active IBD patients according to limited data (SMD = -0.75, p = 0.02). Besides, the percentage of intestinal Tregs was significantly higher in inflamed regions than in non-inflamed regions (SMD = 0.85, p < 0.001). Our study quantitatively summarized the quantitative and functional changes of Tregs and supported the therapeutic potential of Tregs in IBD. Moreover, additional research into the functions and characteristics of intestinal Tregs in IBD is needed.
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Affiliation(s)
- Shihao Duan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yubin Cao
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Pingrun Chen
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yan Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
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Choudhury A, Dhillon J, Sekar A, Gupta P, Singh H, Sharma V. Differentiating gastrointestinal tuberculosis and Crohn's disease- a comprehensive review. BMC Gastroenterol 2023; 23:246. [PMID: 37468869 PMCID: PMC10354965 DOI: 10.1186/s12876-023-02887-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 07/13/2023] [Indexed: 07/21/2023] Open
Abstract
Gastrointestinal Tuberculosis (GITB) and Crohn's disease (CD) are both chronic granulomatous diseases with a predilection to involve primarily the terminal ileum. GITB is often considered a disease of the developing world, while CD and inflammatory bowel disease are considered a disease of the developed world. But in recent times, the epidemiology of both diseases has changed. Differentiating GITB from CD is of immense clinical importance as the management of both diseases differs. While GITB needs anti-tubercular therapy (ATT), CD needs immunosuppressive therapy. Misdiagnosis or a delay in diagnosis can lead to catastrophic consequences. Most of the clinical features, endoscopic findings, and imaging features are not pathognomonic for either of these two conditions. The definitive diagnosis of GITB can be clinched only in a fraction of cases with microbiological positivity (acid-fast bacilli, mycobacterial culture, or PCR-based tests). In most cases, the diagnosis is often based on consistent clinical, endoscopic, imaging, and histological findings. Similarly, no single finding can conclusively diagnose CD. Multiparametric-based predictive models incorporating clinical, endoscopy findings, histology, radiology, and serology have been used to differentiate GITB from CD with varied results. However, it is limited by the lack of validation studies for most such models. Many patients, especially in TB endemic regions, are initiated on a trial of ATT to see for an objective response to therapy. Early mucosal response assessed at two months is an objective marker of response to ATT. Prolonged ATT in CD is recognized to have a fibrotic effect. Therefore, early discrimination may be vital in preventing the delay in the diagnosis of CD and avoiding a complicated course.
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Affiliation(s)
| | | | - Aravind Sekar
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India
| | - Pankaj Gupta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India
| | - Harjeet Singh
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India
| | - Vishal Sharma
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India
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Jalalvand M, Enayati S, Akhtari M, Madreseh E, Jamshidi A, Farhadi E, Mahmoudi M, Amirzargar A. Blood regulatory T cells in inflammatory bowel disease, a systematic review, and meta-analysis. Int Immunopharmacol 2023; 117:109824. [PMID: 36827916 DOI: 10.1016/j.intimp.2023.109824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 01/07/2023] [Accepted: 01/28/2023] [Indexed: 02/24/2023]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is an autoimmune disease involving various parts of the gastrointestinal (GI) tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). Due to the contradictory results regarding the percentage of peripheral blood (PB) regulatory T cells (Tregs) in IBD patients, this meta-analysis aimed to determine the Tregs frequency in IBD patients. METHOD We searched PubMed, Web of Science, SCOPUS, and Google Scholar databases for relevant observational articles that analyzed and reported the frequency of PB Tregs in IBD patients and healthy control groups. After choosing the related articles by two reviewers, the data regarding the definition of Tregs and their frequencies in different groups were recorded. RESULT In 22 studies, the results showed a nonsignificant difference in the frequency of PB Tregs between IBD cases and control subjects (SMD: -0.27, 95 % CI: -0.78, 0.23). However, the frequency of CD4+CD25+CD127- (SMD: -0.89, 95 % CI: -1.52, -0.26) and CD4+CD25+FoxP3+ (SMD: -1.32, 95 % CI: -2.37, -0.26) Tregs were significantly lower in IBD cases, compared to healthy subjects. Also, UC cases and active IBD cases showed a significantly lower frequency of Treg cells, compared to controls and remission IBD cases, respectively (SMD: -0.68, 95 % CI: -1.24, -0.11 and SMD: -0.60, 95 % CI: -0.93, -0.27). CONCLUSION Our study highlighted a probable decrease of Tregs in IBD patients, especially the patients with active states of the disease. The decrease of Treg cells might cause an imbalance in the immune system and the over-activation of auto-immune responses against the digestive tract.
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Affiliation(s)
- Mobina Jalalvand
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Enayati
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Akhtari
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Madreseh
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Jamshidi
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Farhadi
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdi Mahmoudi
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Aliakbar Amirzargar
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Gupta A, Sharma K, Sharma V, Singh J, Nada R, Saikia B, Minz RW, Anand S, Kumar M. Comparative evaluation of interleukin-10, transforming growth factor-β, and interleukin-17 in gastrointestinal tuberculosis and crohn's disease. Int J Mycobacteriol 2022; 11:384-388. [PMID: 36510922 DOI: 10.4103/ijmy.ijmy_131_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) are close mimickers and difficult to discriminate. Recent work has focused on the immunological differences between GITB and CD based on cytokines related to T-regulatory cells and Th17 cells. In the present cross-sectional study, suspected cases of GITB or CD underwent extensive clinical, radiological, endoscopic, histological, and microbiological assessment. The diagnosis was based on standard criteria and response to antitubercular therapy endoscopically. METHODS Interleukin (IL)-10, transforming growth factor-β (TGF-β), and IL-17 were measured and compared between GITB and CD along with other parameters. Fisher's exact test and Mann-Whitney U test were used as per the data type. RESULTS Of the 27 patients, 11 had CD, 9 had GITB, and 7 had other conditions. Chronic diarrhea, involvement of left and long segments of the colon, and aphthous ulcers were significantly more frequent in CD; however, transverse ulcers were in GITB. IL-10 was reduced in both GITB (median-interquartile range [IQR] 9.54 [3.65-24.04]) and CD (median-IQR 13.28 [6.91-22.50]) compared to control (median-IQR 26.72 [10.34-35.43]). TGF-β showed little variation, but IL-17 was below the detection limit in most cases. None of these cytokines were significantly different between CD and GITB. The sensitivity and specificity of multiplex Mycobacterium tuberculosis-polymerase chain reaction were 44.44% and 100%, respectively. CONCLUSION Serum cytokine profiling (IL-10, IL-17, and TGF-β) could not significantly differentiate GITB and CD. Moreover, extensive molecular, transcriptomic, chemokines, and cytokine analyses may shed light on these aspects.
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Affiliation(s)
- Anjali Gupta
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Kusum Sharma
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jagdeep Singh
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ritambhra Nada
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Biman Saikia
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ranjana W Minz
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shashi Anand
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Mahendra Kumar
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Kedia S, Sharma R, Vuyyuru SK, Madhu D, Sahu P, Kante B, Das P, Goyal A, Madan K, Makharia G, Ahuja V. Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis. Intest Res 2022; 20:184-191. [PMID: 33934587 PMCID: PMC9081998 DOI: 10.5217/ir.2020.00104] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 01/17/2021] [Accepted: 01/22/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND/AIMS Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. METHODS Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. RESULTS Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn's disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn's disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%. CONCLUSIONS Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.
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Affiliation(s)
- Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer Kumar Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Deepak Madhu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Ankur Goyal
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Karan Madan
- Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Maulahela H, Simadibrata M, Nelwan EJ, Rahadiani N, Renesteen E, Suwarti SWT, Anggraini YW. Recent advances in the diagnosis of intestinal tuberculosis. BMC Gastroenterol 2022; 22:89. [PMID: 35227196 PMCID: PMC8885312 DOI: 10.1186/s12876-022-02171-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 11/29/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Intestinal tuberculosis still has a high incidence, especially in developing countries. The biggest challenge of this disease is the establishment of the diagnosis because the clinical features are not typical. Investigations such as culture, acid-fast bacilli (AFB) staining, and histopathology have low sensitivity, so other investigations are needed. Latest molecular-based diagnostic modalities such as GeneXpert, interferon-gamma (IFN-γ) release assays (IGRA), polymerase chain reaction (PCR), multiplex-PCR, and immunological markers are expected to help diagnose intestinal tuberculosis. This article review will examine the latest diagnostic modalities that can be used as a tool in establishing the diagnosis of intestinal tuberculosis. RESULTS Through a literature search, we were able to review the diagnostic values of various available diagnostic modalities as the appropriate additional test in intestinal tuberculosis. Culture as a gold standard has a sensitivity and specificity value of 9.3% and 100% with the MGIT BACTEC system as the most recommended medium. The sensitivity values of AFB staining, histopathology examination, GeneXpert, IGRA, PCR, multiplex-PCR and, immunological markers were ranged between 17.3 and 31%; 68%; 81-95.7%; 74-88%; 21.6-65%; 75.7-93.1%; and 52-87%, respectively. Meanwhile the specificity values were 100%; 77.1%; 91-100%; 74-87%; 93-100%; 96.4-100%; and 70-95%, respectively. CONCLUSION The combination of clinical examination, conventional examination, and the latest molecular-based examination is the best choice for establishing the diagnosis of intestinal tuberculosis. Most recent modalities such as multiplex PCR and immunological marker examinations are diagnostic tools that deserve to be used in diagnosing intestinal tuberculosis as their sensitivity and specificity values are quite high and more evidences are expected to support the application of these examinations shortly soon.
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Affiliation(s)
- Hasan Maulahela
- Division of Gastroenterology, Internal Medicine Department, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Central General Hospital, Infectious Diseases and Immunology Research Center, Indonesian Medical Education and Research Institute (IMERI), Jakarta, Indonesia.
| | - Marcellus Simadibrata
- Division of Gastroenterology, Internal Medicine Department, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Central General Hospital, Infectious Diseases and Immunology Research Center, Indonesian Medical Education and Research Institute (IMERI), Jakarta, Indonesia
| | - Erni Juwita Nelwan
- Division of Tropical Medicine and Infectious Diseases, Internal Medicine Department, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo Hospital, Infectious Diseases and Immunology Research Center, Indonesian Medical Education and Research Institute (IMERI), Jakarta, Indonesia
| | - Nur Rahadiani
- Department of Anatomical Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia
| | - Editha Renesteen
- Infectious Diseases and Immunology Research Center, Faculty of Medicine Universitas Indonesia, Indonesian Medical Education and Research Institute (IMERI), Jakarta, Indonesia
| | - S W T Suwarti
- Infectious Diseases and Immunology Research Center, Faculty of Medicine Universitas Indonesia, Indonesian Medical Education and Research Institute (IMERI), Jakarta, Indonesia
| | - Yunita Windi Anggraini
- Infectious Diseases and Immunology Research Center, Faculty of Medicine Universitas Indonesia, Indonesian Medical Education and Research Institute (IMERI), Jakarta, Indonesia
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A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn's disease and intestinal tuberculosis. Sci Rep 2021; 11:23303. [PMID: 34857759 PMCID: PMC8639680 DOI: 10.1038/s41598-021-02383-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 11/09/2021] [Indexed: 11/17/2022] Open
Abstract
Differentiation of Crohn’s disease (CD) from intestinal tuberculosis (ITB) is a big challenge to gastroenterologists because of their indistinguishable features and insensitive diagnostic tools. A non-invasive biomarker is urgently required to distinguish ITB/CD patients particularly in India, a TB endemic region, where CD frequency is increasing rapidly due to urbanization. Among the three differentially expressed miRNAs obtained from small RNA transcriptomic profiling of ileocaecal/terminal ileal tissue of ITB/CD patients (n = 3), only two down-regulated miRNAs, miR-31-5p, and miR-215-5p showed comparable data in qRT-PCR. Out of which, only miR-215-5p was detectable in the patient’s plasma, but there was no significant difference in expression between ITB/CD. On the other hand, miR-375-3p, the pulmonary TB specific marker was found in higher amount in the plasma of ITB patients than CD while reverse expression was observed in the ileocaecal/terminal ileal tissues of the same patients. Next, using Bioplex pro-human cytokine 48-plex screening panel, only three chemokines, Eotaxin-1/CCL11, SDF-1α/CXCL12, and G-CSF have noted significantly different levels in the serum of ITB/CD patients. ROC analysis has revealed that compared to a single molecule, a combination of miR-375-3p + Eotaxin-1/CCL11 + SDF-1α /CXCL12 + G-CSF showed a better AUC of 0.83, 95% CI (0.69–0.96) with 100% specificity and positive predictive value while sensitivity, negative predictive value, and accuracy were 56%, 69%, and 78% respectively in distinguishing ITB from CD. This study suggests that a combination of plasma markers shows better potential in differentiating ITB from CD than a single marker and this panel of markers may be used for clinical management of ITB/CD patients.
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12
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Téllez-Navarrete NA, Ramon-Luing LA, Muñoz-Torrico M, Preciado-García M, Medina-Quero K, Hernandez-Pando R, Chavez-Galan L. Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time. Mol Med 2021; 27:76. [PMID: 34261449 PMCID: PMC8278684 DOI: 10.1186/s10020-021-00320-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 05/27/2021] [Indexed: 01/05/2023] Open
Abstract
Background Tuberculosis (TB) is an infectious disease. During TB, regulatory T cells (Treg) are related to poor prognosis. However, information about conventional and unconventional Treg (cTreg and uTreg, respectively) is limited. The tumour necrosis factor (TNF) and its receptors (TNFR1 and TNFR2) are necessary for mycobacterial infection, and TNFR2 signalling is required to maintain Treg. Methods A blood sample of drug-susceptible (DS-TB) and drug-resistant tuberculosis (DR-TB) patients was obtained before (basal) and after 2 and 6 months of anti-TB therapy. Expression of TNF, TNFR1, and TNFR2 (transmembrane form, tm) on cTreg, uTreg, activated CD4+ (actCD4+), and CD4+ CD25− (CD4+) T cell subpopulations were evaluated. The main objective was to identify immunological changes associated with sensitive/resistant Mtb strains and with the use of anti-TB therapy. Results We found that after 6 months of anti-TB therapy, both DS- and DR-TB patients have decreased the frequency of cTreg tmTNF+, CD4+ tmTNFR1+ and CD4+ tmTNFR2+. Nevertheless, after 6 months of therapy, only DR-TB patients decreased the frequency of actCD4+ tmTNF+ and actCD4+ tmTNFR2+, exhibited a systemic inflammatory status (high levels of TNF, IFN-γ and IL-12), and their purified CD4+ T cells showed that TNF and TNFR2 are up-regulated at the transcriptional level. Moreover, DS- and DR-TB down-regulated TNFR1 and other proteins associated with Treg (FOXP3 and TGFβ1) in response to the anti-TB therapy. Conclusion These results partially explain the differences in the immune response of DS-TB vs DR-TB. The frequency of actCD4+ tmTNFR2+ cells and inflammatory status should be considered in the follow-up of therapy in DR-TB patients. Supplementary Information The online version contains supplementary material available at 10.1186/s10020-021-00320-4.
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Affiliation(s)
- Norma A Téllez-Navarrete
- Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Calzada de Tlalpan No. 4510, CP. 14080, Mexico City, Mexico
| | - Lucero A Ramon-Luing
- Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Calzada de Tlalpan No. 4510, CP. 14080, Mexico City, Mexico
| | - Marcela Muñoz-Torrico
- Clinic of Tuberculosis, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City, Mexico
| | - Mario Preciado-García
- Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Calzada de Tlalpan No. 4510, CP. 14080, Mexico City, Mexico
| | - Karen Medina-Quero
- Laboratory of Immunology, Escuela Militar de Graduados en Sanidad, Mexico City, Mexico
| | - Rogelio Hernandez-Pando
- Experimental Pathology Section, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Leslie Chavez-Galan
- Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Calzada de Tlalpan No. 4510, CP. 14080, Mexico City, Mexico.
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13
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Rampal R, Kedia S, Wari MN, Madhu D, Singh AK, Tiwari V, Mouli VP, Mohta S, Makharia G, Ahuja V. Prospective validation of CD4+CD25+FOXP3+ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn's disease. Intest Res 2021; 19:232-238. [PMID: 32375209 PMCID: PMC8100372 DOI: 10.5217/ir.2019.09181] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/26/2020] [Accepted: 02/28/2020] [Indexed: 01/27/2023] Open
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 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.
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Affiliation(s)
- Ritika Rampal
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Mohamad Nahidul Wari
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Deepak Madhu
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Amit Kumar Singh
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Veena Tiwari
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - V. Pratap Mouli
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Srikant Mohta
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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14
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Kedia S, Ahuja V. Intestinal tuberculosis or Crohn's disease: Illusion or delusion or allusion. JGH Open 2021; 5:177-179. [PMID: 33553652 PMCID: PMC7857303 DOI: 10.1002/jgh3.12495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 01/13/2021] [Indexed: 01/21/2023]
Affiliation(s)
- Saurabh Kedia
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Vineet Ahuja
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
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Banerjee R, Pal P, Mak JWY, Ng SC. Challenges in the diagnosis and management of inflammatory bowel disease in resource-limited settings in Asia. Lancet Gastroenterol Hepatol 2020; 5:1076-1088. [PMID: 33181087 DOI: 10.1016/s2468-1253(20)30299-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 05/15/2020] [Accepted: 05/20/2020] [Indexed: 12/14/2022]
Abstract
Inflammatory bowel disease (IBD) is increasing in prevalence in resource-limited settings in Asia. Although the prevalence of IBD is lower in these settings than in high-income countries, the high disease burden due to large population size is projected to overtake that of high-income countries in the near future. Unique challenges exist for diagnosing and managing IBD in Asia. On one hand, the inadequate disease awareness in physicians and the general population, the scarcity of diagnostic services, the infectious mimics of IBD (specifically intestinal tuberculosis), and the widespread use of empirical antibiotics and antitubercular therapy pose diagnostic challenges. On the other hand, the absence of a centralised health-care delivery system or universal health insurance, the high cost of therapy, limited access to biologics, and the high risk of opportunistic infections with immunosuppressive therapy present therapeutic challenges. The high probability of tuberculosis reactivation often precludes biological therapy because Asia is highly endemic for tuberculosis and has a high prevalence of latent tuberculosis. Current screening strategies are often ineffective in ruling out latent tuberculosis. Hence, management strategies are often modified according to these challenges. This Series paper discusses the challenges in the diagnosis and management of IBD in resource-limited settings in Asia.
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Affiliation(s)
- Rupa Banerjee
- IBD Centre, Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India.
| | - Partha Pal
- IBD Centre, Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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Gupta A, Pratap Mouli V, Mohta S, Kante B, Kalaivani M, Madhu D, Sahu P, Kumar S, Sharma R, Sahni P, Das P, Gupta SD, Makharia G, Kedia S, Ahuja V. Antitubercular Therapy Given to Differentiate Crohn's Disease From Intestinal Tuberculosis Predisposes to Stricture Formation. J Crohns Colitis 2020; 14:1611-1618. [PMID: 32369567 DOI: 10.1093/ecco-jcc/jjaa091] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Treatment trial with antitubercular therapy [ATT] is a common strategy in tuberculosis-endemic countries in case of a diagnostic dilemma between intestinal tuberculosis and Crohn's disease [CD]. Our aim was to determine the long-term clinical course of patients who received ATT before an eventual diagnosis of CD was made. METHODS We performed retrospective comparison between CD patients who received ≥6 months of ATT vs those who did not receive ATT. Outcomes assessed were change in disease behaviour during follow-up, requirement of surgery and medication use. RESULTS In all, 760 patients with CD were screened for the study and, after propensity matching for location and behaviour of disease, 79 patients in each group were compared. Progression from inflammatory [B1] to stricturing/fistulising [B2/B3] phenotype was increased among CD patients who received ATT [B1, B2, B3: 73.4%, 26.6%, 0% at baseline vs: 41.8%, 51.9%, 6.3% at follow-up, respectively] as compared with those who did not receive ATT [B1, B2, B3: 73.4%, 26.6%, 0% at baseline vs: 72.2%, 27.8%, 0% at follow-up, respectively] with an odds ratio of 11.05[3.17-38.56]. The usage of 5-aminosalocylates, steroids, immunosuppressants and anti-tumour necrosis factor was similar between both the groups. On survival analysis, CD patients who received ATT had a lower probability of remaining free of surgery [45%] than those who did not [76%] at 14 years of follow-up (hazard ratio [HR] = 3.22, 95% confidence interval [CI], 1.46-7.12, p = 0.004]. CONCLUSIONS Crohn's disease patients diagnosed after a trial with antitubercular therapy had an unfavourable long-term disease course with higher rate of stricture formation and less chance of remaining free of surgery.
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Affiliation(s)
- Akshita Gupta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Venigalla Pratap Mouli
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Srikant Mohta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mani Kalaivani
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Deepak Madhu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Peush Sahni
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Nayak SS, Shetty MV, Pai CG, Guruprasad KP, Satyamoorthy K. Apoptosis in peripheral blood lymphocytes in intestinal tuberculosis and Crohn's disease: Implications to diagnostic differentiation. Indian J Gastroenterol 2020; 39:338-345. [PMID: 32803718 DOI: 10.1007/s12664-019-01011-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 12/24/2019] [Indexed: 02/04/2023]
Abstract
AIM Intestinal tuberculosis (ITb) and Crohn's disease (CD) mimic each other often leading to misdiagnosis. We evaluated the difference between ITb and CD using the extent of apoptosis in peripheral blood lymphocytes. METHODS CD4+ cells as a percentage of the lymphocytes and viable, dead, total apoptotic, early apoptotic, and late apoptotic CD4+ cells were assessed in the peripheral blood by flow cytometry in healthy controls and patients with confirmed active ITb and CD prior to initiating therapy. Early apoptotic and total apoptotic cells were further expressed as a proportion of the percentage of CD4+ cells. RESULTS The percentages of CD4+ cells (6.5 [3.0, 8.7] vs. 13.40 [10.15, 13.40]; p < 0.001), total apoptotic cells (0.13 [0.0, 0.22] vs. 0.08 [0.0, 0.21]; p = 0.045), early apoptotic (1.24 [0.55, 2.54] vs. 0.71 [0.40, 1.30]; p = 0.037), and the proportion of the latter two parameters (17.18 [5.61, 57.33] vs. 4.84 [2.71, 9.83]; p-value 0.039) and (17.18 [7.4, 67.50] vs. 5.51 [3.10, 11.03]; p-value 0.036) were significantly different between patients with ITb and CD. The best sensitivity, specificity, and positive and negative predictive values for the diagnosis of ITb were seen with the CD4+ cell percentage (82.6%, 82.4%, 86.4%, 77.8%, respectively) and the proportion of early apoptotic cells (73.9%, 70.6%, 77.3%, 66.7%, respectively). CONCLUSION CD4+ cells as a percentage of peripheral blood lymphocytes and the proportion of early apoptotic CD4+ cells show promise to diagnostic differentiation between ITb and CD.
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Affiliation(s)
- Suprabha Suresh Nayak
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576 104, India
| | - Mamatha Vishwanatha Shetty
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576 104, India
| | - Cannanore Ganesh Pai
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576 104, India.
| | - Kanive Parashiva Guruprasad
- School of Life Sciences, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576 104, India
| | - Kapaettu Satyamoorthy
- School of Life Sciences, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576 104, India
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Sharma V. Differentiating intestinal tuberculosis and Crohn disease: Quo Vadis. Expert Rev Gastroenterol Hepatol 2020; 14:647-650. [PMID: 32552311 DOI: 10.1080/17474124.2020.1785870] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 06/18/2020] [Indexed: 01/24/2023]
Affiliation(s)
- Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research , Chandigarh, India
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Pratap Mouli V, Gupta A, Ahuja V. Diagnostic delay due to anti-tubercular therapy in Crohn's disease: A red herring? J Crohns Colitis 2020; 15:jjaa155. [PMID: 32697839 DOI: 10.1093/ecco-jcc/jjaa155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Indexed: 02/08/2023]
Affiliation(s)
- Venigalla Pratap Mouli
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Akshita Gupta
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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Kedia S, Das P, Madhusudhan KS, Dattagupta S, Sharma R, Sahni P, Makharia G, Ahuja V. Differentiating Crohn's disease from intestinal tuberculosis. World J Gastroenterol 2019; 25:418-432. [PMID: 30700939 PMCID: PMC6350172 DOI: 10.3748/wjg.v25.i4.418] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 12/07/2018] [Accepted: 12/14/2018] [Indexed: 02/06/2023] Open
Abstract
Differentiating Crohn's disease (CD) and intestinal tuberculosis (ITB) has remained a dilemma for most of the clinicians in the developing world, which are endemic for ITB, and where the disease burden of inflammatory bowel disease is on the rise. Although, there are certain clinical (diarrhea/hematochezia/perianal disease common in CD; fever/night sweats common in ITB), endoscopic (longitudinal/aphthous ulcers common in CD; transverse ulcers/patulous ileocaecal valve common in ITB), histologic (caseating/confluent/large granuloma common in ITB; microgranuloma common in CD), microbiologic (positive stain/culture for acid fast-bacillus in ITB), radiologic (long segment involvement/comb sign/skip lesions common in CD; necrotic lymph node/contiguous ileocaecal involvement common in ITB), and serologic differences between CD and ITB, the only exclusive features are caseation necrosis on biopsy, positive smear for acid-fast bacillus (AFB) and/or AFB culture, and necrotic lymph node on cross-sectional imaging in ITB. However, these exclusive features are limited by poor sensitivity, and this has led to the development of multiple multi-parametric predictive models. These models are also limited by complex formulae, small sample size and lack of validation across other populations. Several new parameters have come up including the latest Bayesian meta-analysis, enumeration of peripheral blood T-regulatory cells, and updated computed tomography based predictive score. However, therapeutic anti-tubercular therapy (ATT) trial, and subsequent clinical and endoscopic response to ATT is still required in a significant proportion of patients to establish the diagnosis. Therapeutic ATT trial is associated with a delay in the diagnosis of CD, and there is a need for better modalities for improved differentiation and reduction in the need for ATT trial.
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Affiliation(s)
- Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India
| | | | - Siddhartha Dattagupta
- Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Raju Sharma
- Department of Radiology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Peush Sahni
- Department of GI Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
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Ao C, Zeng K. The role of regulatory T cells in pathogenesis and therapy of human papillomavirus-related diseases, especially in cancer. INFECTION GENETICS AND EVOLUTION 2018; 65:406-413. [PMID: 30172014 DOI: 10.1016/j.meegid.2018.08.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 08/13/2018] [Accepted: 08/15/2018] [Indexed: 12/19/2022]
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted agent in the world. It can cause condyloma acuminatum, anogenital malignancies, and head and neck cancers. The host immune responses to HPV involve multiple cell types that have regulatory functions, and HPV-mediated changes to regulatory T cells (Tregs) in both the local lesion tissues and the circulatory system of patients have received considerable attention. The role of Tregs in HPV infections ranges from suppression of effector T cell (Teff) responses to protection of tissues from immune-mediated injury in different anatomic subsites. In this review, we explore the influence of Tregs in the immunopathology of HPV-related diseases and therapies targeting Tregs as novel approaches against HPV.
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Affiliation(s)
- Chunping Ao
- Department of Dermatology and Venereology, Nanfang hospital, Southern Medical University, Guangzhou, 510515, China
| | - Kang Zeng
- Department of Dermatology and Venereology, Nanfang hospital, Southern Medical University, Guangzhou, 510515, China.
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22
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Sabbagh P, Karkhah A, Nouri HR, Javanian M, Ebrahimpour S. The significance role of regulatory T cells in the persistence of infections by intracellular bacteria. INFECTION GENETICS AND EVOLUTION 2018; 62:270-274. [PMID: 29751196 DOI: 10.1016/j.meegid.2018.05.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 04/29/2018] [Accepted: 05/01/2018] [Indexed: 02/07/2023]
Abstract
Regulatory T cells (Treg cells), are considered as effective immune cells playing a key role in immune response during cancers, autoimmune and infectious diseases. Regulatory T lymphocytes are divided into two main subgroups: natural Treg cells that generated during maturation in the thymus and have the suppressive activity that is critical for the establishment and maintenance of homeostasis in the body and induced Treg cells (iTreg) that are originated from naive T cells following the self-antigen recognition. In recent years, the roles of Treg in immune responses to microbial infections have received increased attention in researches. Several reports suggested the pivotal role of Treg cells in controlling responses to bacterial infections and demonstrated the impact of regulatory cells on one or more stages in the pathogenesis of bacterial infections. In this review, we describe the significance of regulatory T cells in the immunopathology of bacterial infections by focusing on specific bacterial infections including Mycobacteria, Listeria monocytogenes, and Bordetella pertussis. Moreover, suppressive mechanisms of regulatory T cells during bacterial infection including cell-cell contact, local secretion of inhibitory cytokines and local competition for growth factors will be discussed.
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Affiliation(s)
- Parisa Sabbagh
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Ahmad Karkhah
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran; Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Hamid Reza Nouri
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Mostafa Javanian
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Soheil Ebrahimpour
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran.
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