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( Ritika Rampal ),( Saurabh Kedia ),( Mohamad Nahidul Wari ),( Deepak Madhu ),( Amit Kumar Singh ),( Veena Tiwari ),( V. Pratap Mouli ),( Srikant Mohta ),( Govind Makharia ),( Vineet Ahuja ) 대한장연구학회 2021 Intestinal Research Vol.19 No.2
Background/Aims: Crohn’s disease (CD) and intestinal tuberculosis (ITB) remain “difficult-to-differentiate” diseases. We have previously documented peripheral blood frequency of CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD. (Intest Res 2021;19:232-238)
Prasenjit Das,Ritika Rampal,Sonakshi Udinia,Tarun Kumar,Sucharita Pilli,Nahid Wari,Imtiaz Khan Ahmed,Saurabh Kedia,Siddhartha Datta Gupta,Dhiraj Kumar,Vineet Ahuja 대한장연구학회 2018 Intestinal Research Vol.16 No.3
Background/Aims: 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 M1ϕ marker) and CD163/CD68 (an M2ϕ marker), and the ratio of M1ϕ to M2ϕ 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: M1ϕ 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, M1ϕ predominance was significant (P=0.001). In iTB, the densities of M1ϕ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1ϕ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients. Conclusions: Proinflammatory M1ϕ 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.