Today's Veterinary Practice

JAN-FEB 2018

Today's Veterinary Practice provides comprehensive information to keep every small animal practitioner up to date on companion animal medicine and surgery as well as practice building and management.

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PEER REVIEWED 30 CE: INFLAMMATORY BOWEL DISEASE Genetics The genetic component believed to be associated with an increased risk of IBD is well documented in humans and involves mutations in pattern recognition receptors such as nucleotide binding oligomerized domain 2, Toll-like receptors (TLRs), and interleukin-23. 1,3,5,8–10,12,14 These receptors sense pathogen-associated molecular patterns in the region of the immediate cell surface or intracellular environment. Specific breeds of dogs are recognized as being prone to chronic enteropathies, which likely suggests a genetic component ( TABLE 1 ). Although a genetic component is not as well recognized in cats, Siamese and other oriental breeds have been suggested to be more predisposed to developing IBD. 22,23 In our experience, this has not necessarily been the case, as domestic shorthaired and longhaired breeds account for most cats presenting and diagnosed at our facility. The pathophysiology behind breed predispositions is not well understood, but triggers have been identified in some breeds. In boxers with granulomatous colitis, genome analysis has identified disease-associated single- nucleotide polymorphisms (SNPs) that may affect killing of pathologic Escherichia coli. The presence of these adherent and invasive E coli within mucosal macrophages of specifically boxers, and this organism's eradication with tailored antibiotic implementation further suggests a breed-specific association relative to disease pathogenesis as well as clinical response. 8,15-18,24,25 Genetic analysis of German shepherds has shown that several SNPs in the TLR 4 and TLR 5 genes are significantly associated with the incidence of lymphocytic–plasmacytic IBD. 26 These TLRs are a class of proteins of the innate immune system that span the membrane of sentinel cells, such as macrophages and dendritic cells, and are important in the recognition of lipopolysaccharide of gram-negative bacteria, lipoteichoic acid of gram-positive bacteria, and bacterial flagellin. TLR 2 mRNA expression, which has been correlated with the clinical severity of IBD, has been noted to be higher in the duodenum of affected dogs compared with healthy dogs. 1 In mouse models, TLR 2 has been implicated in the homeostasis of intestinal tissue after injury. 1,27,28 Mucosal Immune System and Immune Responses The mucosal immune system, immune tolerance, and other innate and adaptive immune processes also play roles in the development of chronic inflammation of the GI tract. Immunoglobulin A (IgA), important in the mucosal defense system, provides a barrier to keep luminal bacteria from crossing the luminal epithelial cells. Loosely and tightly adherent mucus produced by goblet cells and tight junctions between luminal epithelial cells also provide an immediate barrier. Any irregularity in these barriers can lead to the transposition of GI pathogens and commensals and result in chronic inflammation. TABLE 1 Chronic Enteropathies Associated With Specific Dog Breeds DOG BREED ASSOCIATED ENTEROPATHY Soft-coated wheaten terrier Protein-losing enteropathy Basenji Immunoproliferative enteropathy Boxer French bulldog Granulomatous colitis, also known as histiocytic ulcerative colitis 4,8,15-18 German shepherd Lymphocytic-plasmacytic inflammation 4,8,19,20 Norwegian lundehund Inflammatory bowel disease 21 Yorkshire terrier Protein-losing enteropathy with lymphangiectasia a a Protein-losing enteropathy with lymphangiectasia in Yorkshire terriers can have an inflammatory component causing lymphatic dilation; often, IBD is a secondary diagnosis to lymphangiectasia in these dogs.

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