Advances in the study of biomarkers related to canine leishmaniosis

Abstract

This PhD was focused in provide advances in the diagnosis and monitoring of canine leishmaniasis from a laboratory point of view. Therefore, it has the following objectives: - To advance in the use of acute phase proteins (APPs) for the classification and monitoring of the disease. For this purpose, we developed a guideline about the use of APPs for the characterization and management of canine leishmaniasis. Then we compared this guideline with the Leishvet and Canine Leishmaniosis Working Group (CLWG) classifications. Finally, we described how other diseases such as pyometra, pancreatitis or obesity have a totally different pattern of change in APPs compared to canine leishmaniosis. - To apply new biomarkers of kidney damage in canine leishmaniosis (CanL) that help monitor kidney during the treatment of canine leishmaniasis and that could provide information on the response to treatment. For this, various markers of glomerular and tubular damage such as urinary IgG/creatinine have been measured and compared. - To advance in the use of saliva, as a non-invasive sample in this disease. For this purpose we validated and used saliva, for the determination of urea and creatinine in dogs with canine leishmaniosis. - To detect new biomarkers of this disease by the use of proteomic techniques that are very sensitive to detect proteins and could provide a detailed global analysis of expressed proteins in serum of dog before and after treatment. For this, use the Tandem Mass Tag (TMT) isobaric label-based proteomic approach. The conclusions that have been obtained in this doctoral thesis are: 1. APPs concentration can be a useful clinical tool to characterize and manage CanL. The classification system based on the APP created in this PhD correlated with previous classifications systems based in clinical signs and other laboratory analysis. 2. Ferritin and CRP show a particular profile in canine leishmaniosis with a moderate increase in CRP and a higher increase in fold in ferritin that in CRP, which is different than other diseases such as pancreatitis, pyometra or obesity. In addition, ferritin and CRP were useful to monitor the treatment of leishmaniosis. 3. Urinary IgG/creatinine showed a higher accuracy to monitor the kidney disease during the treatment of canine leishmaniosis in dogs with proteinuria than sSDMA or sCre. 4. Urea and creatinine can be measured in saliva of dogs and are increased in chronic renal failure produced by leishmaniosis. 5. TMT isobaric labels could be used to identify new biomolecules that allow a better understanding of the physiopatological mechanism involved in canine leishmaniasis and also that could be potentially used as a biomarker of this disease.