Abstract
Inflammatory bowel disease (IBD) is difficult to diagnose due to nonspecific and variable symptoms, and lack of reliable diagnostic tests. Current methods are invasive, non-sensitive, non-predictive, and do not easily discriminate between its two main forms. Consequently, there remains a great need for reliable serum markers for IBD. Here, using a longitudinal study of various mouse models of colitis, we identified a serum miRNA signature that indicated the development of colitis and discriminated between inflammations of various origins (colitis from arthritis). Unlike the existing biomarkers, the newly identified signature also serves to distinguish individuals at risk, predict the type of inflammation, and evaluate the response to therapeutics. Moreover, the miRNA signature identified in mice predicted ulcerative colitis with 83.3% accuracy. In future, the signature identified herein could play a central role in monitoring inflammatory disorders and therapeutic responses in patients, thereby paving the way for personalized medicine.
Highlights
In human, many disorders are difficult to diagnose due to presence of nonspecific and variable symptoms, and lack of reliable diagnostic tests
Circulating microRNAs have recently emerged as promising non-invasive biomarkers for Inflammatory bowel disease (IBD). miRNAs are small noncoding RNAs (18–25 nucleotides) that play important roles in regulating various biological processes via the post-transcriptional gene expression changes induced by their binding to the 3′-untranslated regions of target mRNAs18. miRNAs are present in extracellular human body fluids in a highly stable form, making them a promising candidate for use as blood biomarkers for IBD and various other diseases19. miRNAs are frequently dysregulated in pathological conditions, and reports have shown that they have a great potential as markers for various diseases, mostly cancers[20,21,22]
In vitro studies have shown that IL-10 inhibits the production of IL-12 and Tumor Necrosis Factor-alpha (TNF-α), and T cell proliferation, and may promote the formation of antigen-specific regulatory T cells[28, 29]
Summary
Many disorders are difficult to diagnose due to presence of nonspecific and variable symptoms, and lack of reliable diagnostic tests. An inquiry of patient medical history, description of symptoms (abdominal pain, cramping, diarrhea, rectal bleeding, and extreme fatigue), physical examination and a combination of tests that includes blood tests and endoscopic procedure is the conventional diagnosis process, with colonoscopy usually prescribed to assess the endoscopic appearance of the colon. This technique is not ideal for monitoring disease activity: it is expensive, burdensome for patients, requires sedation, and carries a small (0.05%) but relevant risk of serious complications, including perforation and death[7]. Circulating microRNAs (miRNAs) have recently emerged as promising non-invasive biomarkers for IBD. miRNAs are small noncoding RNAs (18–25 nucleotides) that play important roles in regulating various biological processes via the post-transcriptional gene expression changes induced by their binding to the 3′-untranslated regions of target mRNAs18. miRNAs are present in extracellular human body fluids (e.g., serum, plasma, saliva, and urine) in a highly stable form, making them a promising candidate for use as blood biomarkers for IBD and various other diseases19. miRNAs are frequently dysregulated in pathological conditions, and reports have shown that they have a great potential as markers for various diseases, mostly cancers[20,21,22]
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