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.
Highlights
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 meta-analysis study with pathological features from biopsy samples revealed that confluent, large, multiple granulomas; granuloma with surrounding cuffing lymphocytes, and caseating necrosis are common in Intestinal tuberculosis (ITB) and the diagnostic specificity of these features have been found high (99%, 95%, and 100% respectively) but sensitivity was very poor (38%, 41%, and 21% respectively) the area under curve (AUC) was high (0.94, 0.90 and 0.99 respectively) in each case[13]
All the ITB patients were positive in multiplex PCR with IS6110 and MBP64 primers while CD patients were negative
Summary
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. 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. CRP C-Reactive protein G-CSF Granulocyte colony stimulating factor HIV Human immunodeficiency virus IBD Inflammatory bowel disease ITB Intestinal tuberculosis LOXL-2 Lysyl oxidase homolog 2 miRNA Micro RNA MTB Mycobacterium tuberculosis NGS generation sequencing NPV Negative predictive value PCR Polymerase chain reaction PPV Positive predictive value pTB Pulmonary tuberculosis qRT-PCR Quantitative real-time PCR RIN RNA integrity ROC Receiver operating curve analysis SDF-1α Stromal cell derived factor-1α. In 2018, Tiwari et al first tested the non-invasive biomolecule for similar goal They showed CD4+CD25+CD127-FOXP3+T reg cells in the peripheral blood have high diagnostic potential (75% sensitivity and 90.6% specificity) in separating CD and ITB4. Exploring the serum proteomic profiling of 30 CD and 21 ITB samples, Zhang et al in 2016 has identified two proteins, [Appetite peptide and Lysyl Oxidase Like 2 (LOXL-2)] which are deregulated in ITB/CD and showed high prediction potential with 76% sensitivity and 80% s pecificity[18], but none of them were validated due to technical limitations
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