ABSTRACT
BACKGROUND: Current tests for diagnosing liver disease in dogs are sub-optimal. MicroRNA-122 (miR-122) is a sensitive and specific biomarker of liver injury in humans and rodents. Circulating miR-122 could have utility in identifying dogs with liver disease. OBJECTIVE: Establish the reference interval for miR-122 in healthy dogs and determine performance in a range of dog breeds with liver disease and control animals with non-liver disease. ANIMALS: Stored serum from 120 healthy dogs, 100 dogs with non-liver diseases, and 30 dogs with histologically confirmed liver disease was analyzed. METHODS: Retrospective study. Medical records of dogs with liver disease, non-liver disease and healthy dogs were reviewed. Serum miR-122 concentrations were measured by PCR and compared with the characteristics of the dogs and their conventional clinical measurements. RESULTS: In healthy dogs the 2.5th, 50th, and 97.5th quartiles of miR-122 were 110 (90% CI 80-114), 594 (505-682), and 3312 (2925-5144) copies/µL, respectively. There was no difference between healthy dogs and dogs with non-liver disease (median ± IQR: healthy dogs 609 [327-1014] copies/µL; non-liver disease 607 [300-1351] copies/µL). miR-122 was higher in dogs with liver disease (11 332 [4418-20 520] copies/µL, P < .001 compared to healthy dogs). miR-122 identified dogs with liver disease with high accuracy (receiver operating characteristic area under curve for comparison with healthy dogs: 0.93 [95% CI 0.86-0.99]). The upper limit of normal for healthy dogs (3312 copies/µL) had a sensitivity of 77% and specificity of 97% for identifying liver disease. CONCLUSION AND CLINICAL IMPORTANCE: Liver disease can be sensitively and specifically diagnosed in dogs by measurement of miR-122.
Subject(s)
Dog Diseases/blood , Liver Diseases/veterinary , MicroRNAs/metabolism , Animals , Biomarkers , Dog Diseases/diagnosis , Dogs , Female , Liver Diseases/blood , Liver Diseases/diagnosis , Male , MicroRNAs/blood , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Exosomes, first isolated 30 years ago, are nanoscale vesicles shed by most types of cells. The nucleic acid rich content of these nanoparticles, floating in virtually all bodily fluids, has great potential for non-invasive molecular diagnostics and may represent a novel therapeutic delivery system. However, current isolation techniques such as ultracentrifugation are not convenient and do not result in high purity isolation. This represents an interesting challenge for microfluidic technologies, from a cost-effective perspective as well as for enhanced purity capabilities, and point-of-care acquisition and diagnosis. In this frontier review, we present the current challenges, comment the first microfluidic advances in this new field and propose a roadmap for future developments. This review enables biologists and clinicians familiar with exosome enrichment to assess the performance of novel microfluidic devices and, equally, enables microfluidic engineers to educate themselves about this new class of promising biomarker-rich particles and the challenges arising from their clinical use.
