|dc.description.abstract||Inflammatory bowel disease (IBD) is a common condition in dogs that is challenging to diagnose. A dysregulated innate immunity plays a major role in its pathogenesis, and surrogate inflammatory markers that reflect disease severity would be clinically useful. S100A12, a damage-associated molecular pattern molecule, is involved in phagocyte activation. S100A12 binds to the receptor of advanced glycation end products (RAGE), a pattern-recognition receptor, and results in human studies suggest a role of S100A12 and RAGE in chronic inflammation. Soluble RAGE (sRAGE), a decoy receptor, functions as an anti-inflammatory molecule. S100A12 and RAGE/sRAGE have not been studied in canine IBD. Canine S100A12 has not been purified, and while an immunoassay for measurement of S100A12 in humans is available, human antibodies do not cross-react with canine S100A12 (cS100A12). Canine RAGE has been cloned and characterized.
The aims of this project were to purify and partially characterize cS100A12, to develop and analytically validate an immunoassay for cS100A12, and to determine the relationship between cS100A12 and systemic sRAGE concentrations and clinical, endoscopic, and histologic disease severity in dogs with IBD. Markers of gastrointestinal inflammation were also evaluated in dogs with acute hemorrhagic diarrhea syndrome (AHDS).
Canine S100A12 was successfully purified from canine whole blood, and a competitive liquid-phase radioimmunoassay was developed and analytically validated. Fecal cS100A12 concentrations were shown to be increased in dogs with IBD and were associated with clinical disease activity, the severity of endoscopic lesions, and the severity of colonic inflammation. Serum sRAGE concentrations were decreased in dogs with IBD, but were not correlated with disease severity, cS100A12 concentrations, or outcome. Dogs that were euthanized had higher fecal cS100A12 concentrations than dogs that were alive at the end of the study, and serum sRAGE concentrations increased only in IBD dogs with complete clinical remission. A significant but transient increase in fecal cS100A12 was also seen in dogs with AHDS.
Fecal cS100A12 may be clinically useful as a biomarker of inflammation in dogs with IBD, and the sRAGE/RAGE axis appears to be altered in canine IBD. Lack of correlation between sRAGE and cS100A12 is consistent with sRAGE being a non-specific decoy receptor.||