A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis

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 Ind...

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Autores principales: 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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spelling oai:doaj.org-article:b8c35cf50bdb4a719b09ac949885c8e72021-12-05T12:12:09ZA combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis10.1038/s41598-021-02383-z2045-2322https://doaj.org/article/b8c35cf50bdb4a719b09ac949885c8e72021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02383-zhttps://doaj.org/toc/2045-2322Abstract 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.Susree RoySuchandrima GhoshMallica BanerjeeSayantan LahaDipanjan BhattacharjeeRajib SarkarSujay RayArko BanerjeeRanajoy GhoshAniket HalderAlakendu GhoshRaghunath ChatterjeeSimanti DattaGopal Krishna DhaliSoma BanerjeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
description 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.
format article
author 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
author_facet 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
author_sort Susree Roy
title A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
title_short A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
title_full A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
title_fullStr A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
title_full_unstemmed A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn’s disease and intestinal tuberculosis
title_sort combination of circulating microrna-375-3p and chemokines ccl11, cxcl12, and g-csf differentiate crohn’s disease and intestinal tuberculosis
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/b8c35cf50bdb4a719b09ac949885c8e7
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