Serum Circulating MicroRNAs as a Marker for Canine Lymphocytic-Plasmacytic Inflammatory Bowel Disease
A.O. Konstantinidis1; T.S. Rallis1; M. Gazouli2; E. Legaki2; G.D. Brellou1; I. Savvas1; K.K. Adamama-Moraitou1; D. Pardali1; A.E. Jergens3; K. Allenspach3
MicroRNAs (miRs) are small, non-coding RNA molecules with gene regulatory function. MiRs appear to play a critical role in the pathogenesis of a variety of diseases in humans, including inflammatory bowel disease (IBD). Furthermore, recent studies suggest that miRs have altered expression profiles in the serum of humans with IBD, suggesting they could be promising non-invasive serum biomarkers.
The aim of the current study was to evaluate the expression of a selection of serum circulating miR-16, miR-21, miR-122, miR146a, miR-147, miR-185, miR-192 and miR-223 in canine lymphocytic-plasmacytic (LP) IBD based on published data on human IBD.
Serum samples were collected from 21 dogs diagnosed with active LP IBD. All dogs had undergone upper and/or lower GI endoscopy according to clinical signs, were diagnosed histopathologically according to the guidelines of the WSAVA International Gastrointestinal Standardization Group (Washabau et al. 2010) and by clinical exclusion diagnosis. In addition, serum samples were available from 14 clinically healthy control dogs for comparison. Total RNA from serum was isolated using Trizol, and reverse transcribed into cDNA. The expression of serum miRs genes was measured using real-time quantitative reverse transcriptase polymerase chain reaction (real-time qRT-PCR). Clinical disease activity was recorded for all dogs using the Canine Chronic Enteropathy Clinical Activity Index (CCECAI; Allenspach et al. 2008). Endoscopies were performed and graded according to the canine IBD endoscopic index (Slovak et al. 2014).
Compared to healthy controls, there was a significantly increased expression of the following miR in the serum of dogs: miR-16 (IBD: median 1.56, range 1.24–1.89, p<0.0005; controls: median 1.4, range 0.89–1.64), miR-21 (IBD: median 1.85, range 0.87–6.89; controls: median 1.54, range 0.37–2.18; p= 0.009), miR-122 (IBD: median 1.85, range 1.08–6.28; controls: median 1.49, range 1.02–2.21; p=0.012), miR146a (IBD: median 1.86, range 0.93–5.92; controls: median 1.575, range 1.33–2.33; p=0.016) and miR-147 (IBD: median 3.63, range 2.73–5.46, p<0.005; controls: median 1.85, range 1.27–2.53, p<0.0005), as well as a significantly decreased expression of miR-185 (IBD: median 0.86, range 0.44–1.53, p<0.0005; controls: median 1.68, range 0.89–1.64, p<0.0005), miR-192 (IBD: median 1.56, range 1.24–1.89, p<0.0005; controls: median 1.4, range 1.19–2.3, p<0.0005) and miR-223 (IBD: median 0.54, range 0.32–0.96, p<0.0005; controls: median 0.9, range 0.62–1.68, p<0.0005).
This study shows that some circulating miRs are differentially expressed in the serum of dogs with LP IBD versus healthy dogs. Further studies are needed to evaluate the usefulness of these markers in the diagnosis and treatment of canine IBD.
Disclosures
No disclosures to report.