The plasma proteome and the acute phase protein response in canine pyometra

Abstract

Canine pyometra is a common inflammatory disease of uterus in sexually mature bitches caused by secondary bacterial infection, leading to change in plasma proteins associated with the innate immune system. Proteomic investigation is increasingly being applied to canine diseases in order to identify and quantify significant changes in the plasma proteome. The aim of the study was to assess and quantify changes in plasma proteome profiles of healthy dogs and pyometra affected bitches using a TMT-based high-resolution quantitative proteomic approach. As a result, 22 proteins were significantly down-regulated including transthyretin, antithrombin, retinol-binding protein, vitamin D binding protein, paraoxonase 1, and kallikrein, while 16 were significantly up-regulated including haptoglobin light chain, alpha-1-acid glycoprotein, C-reactive protein precursor, and lipopolysaccharide-binding protein in dogs with pyometra. Pathway analysis indicated that acute inflammatory response, regulation of body fluid levels, protein activation cascade, the humoral immune response, and phagocytosis were affected in pyometra. Validation of biological relevance of the proteomic study was evident with significant increases in the concentrations of haptoglobin, C-reactive protein, alpha-1-acid glycoprotein, and ceruloplasmin by immunoassay. Pyometra in bitches was shown to stimulate an increase in host defence system proteins in response to inflammatory disease including the acute phase proteins. SignificanceThe label-based high-resolution quantitative proteomics analysis and bioinformatic approach used in this study provide insight into the complex pathophysiology of inflammation associated with pyometra revealing proteins with biomarker potential. Early diagnosis and therapeutic intervention may prevent severe complications associated with advancing sepsis in dogs with pyometra. Therefore the identification of diagnostic biomarkers that, after clinical validation may be used in veterinary practice and protein relevant to pathways responding to disease are important findings of the study. Data are available via ProteomeXchange with identifier PXD015951.