What are the potential biomarkers that should be considered in diagnosing and managing canine chronic inflammatory enteropathies?

Abstract

Chronic inflammatory enteropathies in dogs are characterized by persistent or recurrent gastrointestinal signs that last for more than 3 weeks. Despite unclear etiopathogenesis, it is considered that a genetic predisposition associated with environmental factors, such as dietary antigens and intestinal microbiota, might induce an abnormal immune response in the host. The diagnosis of this condition requires full investigation in order to exclude all other possible causes. Currently, the observation of clinical signs associated with histopathologic evaluation and systematic therapeutic trials is the gold standard for the diagnosis of chronic enteropathies. Furthermore, diagnosis, monitoring the disease progression, and treatment response evaluation can be exhausting, since this whole process is time-consuming, costly, and partially invasive. Therefore, biomarkers appear as non-invasive tools, which can be useful in evaluating gastrointestinal function, identifying the presence of the disease and assessing its natural progression, monitoring gastrointestinal inflammation, predicting response to treatment, and clinical outcomes. Over the past decade, several studies were conducted in order to explore the clinical utility of biomarkers. Thus, the aim of this dissertation is to provide an overview of the biomarkers considered relevant in the diagnosis and management of dogs with chronic inflammatory enteropathies. The biomarkers addressed in this study may be serological, present in urine and feces, or even tissue-derived. This study argues that biomarkers, in particular calprotectin and calgranulin C, have great potential to be used in clinical practice in the diagnosis and management of affected dogs. However, a single biomarker cannot assuredly predict disease severity, progression, response to treatment, and clinical outcomes. Therefore, in order to achieve greater accuracy, it would be beneficial if these tools are used in conjunction with contemporary ones. Future research is needed with the aim to better determine the usefulness of these tools in chronic inflammatory enteropathies in dogs.

Keywords: Biomarkers; Chronic enteropathies; Dog; Inflammatory bowel disease.

Fig. 1.. The intestinal immune system in canine chronic inflammatory enteropathies. The intestinal barrier has increased permeability in dogs with CIE. An impaired barrier function can increase the exposure of immune cells to luminal antigens. These can be tolerated or reacted against, based on the PRRs, such as TLRs. Innate response is based on the interaction of IECs, neutrophils, macrophages, DCs, and eosinophils, as well as their secreted products. After innate immunologic mechanisms, activated APCs trigger an adaptive immune response by presenting peptide antigens to naïve CD4+ T helper cells in secondary lymphoid organs, such as the mesenteric lymph node. Based on their cytokine profile, Th cells can be differentiated into Th1, Th2, Th17 cells, and Tregs, and consequently produce their respective cytokines. In addition, intestinal B lymphocytes have the ability to turn into plasma cells and produce IgA antibodies, which contribute to immune protection. (Original illustration based on: Abraham and Cho, 2009; Allenspach, 2011; Eissa et al., 2019).