Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Abstract

Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food-responsive, antibiotic-responsive, or immunosuppressant-responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein-losing enteropathy. Disease-independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α₁ -proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C-reactive protein, perinuclear anti-neutrophilic cytoplasmic antibodies, 3-bromotyrosine, N-methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

Keywords: antibiotic-responsive enteropathy; dog; food-responsive enteropathy; inflammation; inflammatory bowel disease.

Figure 1

Groups of biomarkers in dogs with chronic inflammatory enteropathies (CIE). The figure shows the functional, biochemical, metabolomic, microbiomic, genomic, and cellular biomarkers that have been evaluated in dogs with CIE. MMA, methylmalonic acid; pANCA, perinuclear anti‐neutrophilic cytoplasmic antibodies; RAGE, receptor for advanced glycation end products; SNP, single‐nucleotide polymorphism