GSE176255
A combination of circulating microRNA-375-3p, and chemokines CCL-11, CXCL12, and G-CSF differentiate Crohn's Disease and Intestinal Tuberculosis
Differentiation of Crohn's disease (CD) from intestinal tuberculosis (ITB) is a big challenge to the gastroenterologists because of their indistinguishable features and insensitive diagnostic tools. A non-invasive biomarker is urgently required to distinguish CD/ITB patients particularly in India, a TB endemic region, where CD frequency is increasing rapidly due to urbanization. Small RNA next generation sequencing (NGS), qRT-PCR, Bioplex pro-human cytokine screening panel-48-plex was employed to identify diagnostic marker for CD and ITB. Graphpad Prism 7 and R software were used for statistics and Receiver operative curve (ROC) analysis respectively. Among the three differentially expressed miRNAs obtained from transcriptomic profiling of ileocecal/terminal ileal tissue of ITB/CD patients (n=3), only two down-regulated miRNAs, miR-31-3p, 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 and 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 ileocecal/terminal tissue of the patients. Next, among 48 cytokine/chemokines,  three chemokines, Eotaxin/CCl11, SDF-1a/CXCl12 and G-CSF were noted significantly different level in the serum of ITB and CD patients.   ROC analysis has revealed that compared to a single molecule, a combination of miR-375-3p+Eotaxin/CCL11+SDF-1/CXCL12+G-CSF has better AUC of 0.83, 95%CI (0.69-0.96) with 100% specificity and positive prediction while sensitivity, negative prediction and accuracy were 56%, 69% and 78% in distinguishing ITB from CD respectively. This study suggests that the plasma markers, when assesed in combination, show high potential to distinguish ITB from CD and thus may help in the clinical management of ITB/CD patients. Overall design: Normal non-inflammed, Crohn's Disease, Intestinal Tuberculosis Liver tissue Samples contributor: Medgenome Inc.