Correlation of disease markers with clinical, endoscopic, and histologic findings in dogs with chronic gastrointestinal inflammation
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Keywords

calgranulin, calprotectin, C-reactive protein, S100A12 protein.

How to Cite

de Oliveira-Barros, L. M., Holanda, A. G. A., Heilmann, R., Steiner, J. M., de Queiroz, G. F., Catão-Dias, J. L., & Matera, J. M. (2025). Correlation of disease markers with clinical, endoscopic, and histologic findings in dogs with chronic gastrointestinal inflammation . Brazilian Journal of Veterinary Medicine, 47(1), e001225. https://doi.org/10.29374/2527-2179.bjvm001225

Abstract

The aim of this study was to evaluate serum and fecal biomarkers in dogs with chronic gastrointestinal inflammation and investigate their associations with clinical, endoscopic, and histopathological findings. Twenty dogs with chronic gastrointestinal signs and twenty clinically healthy control dogs were included. Dogs in the diseased group underwent clinical assessment, gastrointestinal endoscopy, and histopathological evaluation of intestinal biopsies. Serum concentrations of C-reactive protein (CRP), folate, cobalamin, calprotectin, and S100A12, as well as fecal concentrations of calprotectin and S100A12, were measured. Dogs with gastrointestinal inflammation showed significantly higher serum CRP and fecal calprotectin concentrations compared to healthy controls. Serum CRP was positively correlated with clinical disease activity scores and histologic severity in the colon. No significant differences in serum calprotectin or S100A12 concentrations were observed between groups. These findings suggest that serum CRP may serve as a supportive marker of disease severity and that fecal calprotectin holds promise as a non-invasive indicator of intestinal inflammation. In contrast, serum calprotectin and S100A12 showed limited diagnostic utility in this context. Overall, this study provides preliminary insights into the role of selected biomarkers in dogs with chronic gastrointestinal inflammation.

https://doi.org/10.29374/2527-2179.bjvm001225
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References

Allenspach, K. (2013). Diagnosis of small intestinal disorders in dogs and cats. The Veterinary Clinics of North America. Small Animal Practice, 43(6), 1227-1240, v. http://doi.org/10.1016/j.cvsm.2013.07.001. PMid:24144087.

Allenspach, K., Wieland, B., Gröne, A., & Gaschen, F. (2007). Chronic enteropathies in dogs: Evaluation of risk factors for negative outcome.Journal of Veterinary Internal Medicine,21(4), 700-708.http://doi.org/10.1111/j.1939-1676.2007.tb03011.x. PMid:17708389.

Berghoff, N., Parnell, N. K., Hill, S. L., Suchodolski, J. S., & Steiner, J. M. (2013). Serum cobalamin and methylmalonic acid concentrations in dogs with chronic gastrointestinal disease. American Journal of Veterinary Research, 74(1), 84-89. http://doi.org/10.2460/ajvr.74.1.84. PMid:23270350.

Berghoff, N., Suchodolski, J. S., & Steiner, J. M. (2006). Assessment of stability and determination of a reference range for canine c-reactive protein in serum. In: Research Abstract Program of the 24th Annual ACVIM Forum Louisville, KY, May 31 - June 3, 2006. Journal of Veterinary Internal Medicine, 20(3), 697-802. http://doi.org/10.1111/j.1939-1676.2006.tb02919.x.

Carney, P. C., Ruaux, C. G., Suchodolski, J. S., & Steiner, J. M. (2011). Biological variability of C-Reactive protein and specific canine pancreatic lipase immunoreactivity in apparently healthy dogs. Journal of Veterinary Internal Medicine, 25(4), 825-830. http://doi.org/10.1111/j.1939-1676.2011.0729.x. PMid:21564294.

Covin, M. A., & Steiner, J. M. (2022). Measurement and clinical applications of C-reactive protein in gastrointestinal diseases of dogs. Veterinary Clinical Pathology, 50(Supp 1), 29-36. http://doi.org/10.1111/vcp.13100. PMid:35014071.

Dandrieux, J. R. S. (2016). Inflammatory bowel disease versus chronic enteropathy in dogs: Are they one and the same? The Journal of Small Animal Practice, 57(11), 589-599. http://doi.org/10.1111/jsap.12588. PMid:27747868.

Day, M. J., Bilzer, T., Mansell, J., Wilcock, B., Hall, E. J., Jergens, A., Minami, T., Willard, M., Washabau, R., & World Small Animal Veterinary Association Gastrointestinal Standardization Group. (2008). Histopathological Standards for the Diagnosis of Gastrointestinal Inflammation in Endoscopic Biopsy Samples from the Dog and Cat: A Report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group. Journal of Comparative Pathology, 138(Suppl 1), S1-S43. http://doi.org/10.1016/j.jcpa.2008.01.001. PMid:18336828.

Dossin, O. (2011). Laboratory tests for diagnosis of gastrointestinal and pancreatic diseases. Topics in Companion Animal Medicine, 26(2), 86-97. http://doi.org/10.1053/j.tcam.2011.02.005. PMid:21596348.

Dupouy-Manescau, N., Méric, T., Sénécat, O., Drut, A., Valentin, S., Leal, R. O., & Hernandez, J. (2024). Updating the classification of chronic inflammatory enteropathies in dogs. Animals (Basel), 14(5), 681. http://doi.org/10.3390/ani14050681. PMid:38473066.

Equilino, M., Théodoloz, V., Gorgas, D., Doherr, M. G., Heilmann, R. M., Suchodolski, J. S., Steiner, J. M., & Burgener, D. V. M. (2015). Evaluation of serum biochemical marker concentrations and survival time in dogs with protein-losing enteropathy. Journal of the American Veterinary Medical Association, 246(1), 91-99. http://doi.org/10.2460/javma.246.1.91. PMid:25517330.

Fukunaga, S., Kuwaki, K., Mitsuyama, K., Takedatsu, H., Yoshioka, S., Yamasaki, H., Yamauchi, R., Mori, A., Kakuma, T., Tsuruta, O., & Torimura, T. (2017). Detection of calprotectin in inflammatory bowel disease: Fecal and serum levels and immunohistochemical localization. International Journal of Molecular Medicine. http://doi.org/10.3892/ijmm.2017.3244. PMid:29115397.

Grützner, N., Heilmann, R. M., Cranford, S. M., Holzenburg, A., Suchodolski, J. S., & Steiner, J. M. (2015). Inflammatory, immunological, and intestinal disease biomarkers in Chinese Shar-Pei dogs with marked hypocobalaminemia. Journal of Veterinary Diagnostic Investigation, 27(1), 31-40. http://doi.org/10.1177/1040638714560881. PMid:25525135.

Heilmann, R. M., & Steiner, J. M. (2018). Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs. Journal of Veterinary Internal Medicine, 32(5), 1495-1508. http://doi.org/10.1111/jvim.15247. PMid:30222209.

Heilmann, R. M., Berghoff, N., Mansell, J., Grützner, N., Parnell, N. K., Gurtner, C., Suchodolski, J. S., & Steiner, J. M. (2018). Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies. Journal of Veterinary Internal Medicine, 32(2), 679-692. http://doi.org/10.1111/jvim.15065. PMid:29460444.

Heilmann, R. M., Grellet, A., Allenspach, K., Lecoindre, P., Day, M. J., Priestnall, S. L., Toresson, L., Procoli, F., Grützner, N., Suchodolski, J. S., & Steiner, J. M. (2014). Association between fecal S100A12 concentration and histologic, endoscopic, and clinical disease severity in dogs with idiopathic inflammatory bowel disease. Veterinary Immunology and Immunopathology, 158(3-4), 156-166. http://doi.org/10.1016/j.vetimm.2014.01.006. PMid:24518653.

Heilmann, R. M., Grützner, N., Iazbik, M. C., Lopes, R., Bridges, C. S., Suchodolski, J. S., Couto, C. G., & Steiner, J. M. (2017). Hyperhomocysteinemia in greyhounds and its association with hypofolatemia and other clinicopathologic variables. Journal of Veterinary Internal Medicine, 31(1), 109-116. http://doi.org/10.1111/jvim.14597. PMid:27864850.

Heilmann, R. M., Jergens, A. E., Ackermann, M. R., Barr, J. W., Suchodolski, J. S., & Steiner, J. M. (2012). Serum calprotectin concentrations in dogs with idiopathic inflammatory bowel disease. American Journal of Veterinary Research, 73(12), 1900-1907. http://doi.org/10.2460/ajvr.73.12.1900. PMid:23176415

Heilmann, R. M., Nestler, J., Schwarz, J., Grützner, N., Ambrus, A., Seeger, J., Suchodolski, J. S., Steiner, J. M., & Gurtner, C. (2019). Mucosal expression of S100A12 (calgranulin C) and S100A8/A9 (calprotectin) and correlation with serum and fecal concentrations in dogs with chronic inflammatory enteropathy. Veterinary Immunology and Immunopathology, 211, 64-74. http://doi.org/10.1016/j.vetimm.2019.04.003. PMid:31084897.

Jablonski Wennogle, S. A., Priestnall, S. L., & Webb, C. B. (2017). Histopathologic Characteristics of Intestinal Biopsy Samples from Dogs With Chronic Inflammatory Enteropathy With and Without Hypoalbuminemia. Journal of Veterinary Internal Medicine, 31(2), 371-376. http://doi.org/10.1111/jvim.14669. PMid:28256026.

Jandel, A. N., Heilmann, R. M., Sander, H., Steiner, J. M., Grützner, N., & Xenoulis, P. G. (2023). Serumα1-Proteinase inhibitor, calprotectin, and S100A12 concentrations in the characterization of pancreatitis in dogs. Veterinary Sciences, 10(7), 428. http://doi.org/10.3390/vetsci10070428. PMid:37505833.

Jergens, A. E., & Heilmann, R. M. (2022). Canine chronic enteropathy: Current state-of-the-art and emerging concepts. Frontiers in Veterinary Science, 9, 923013. http://doi.org/10.3389/fvets.2022.923013. PMid:36213409.

Jergens, A. E., Crandell, J., Morrison, J. A., Deitz, K., Pressel, M., Ackermann, M., Suchodolski, J. S., Steiner, J. M., & Evans, R. (2010). Comparison of oral prednisone and prednisone combined with metronidazole for induction

therapy of canine inflammatory bowel disease: A randomized-controlled trial. Journal of Veterinary Internal Medicine, 24(2), 269-277. http://doi.org/10.1111/j.1939-1676.2009.0447.x. PMid:20051005.

Jergens, A. E., Schreiner, C. A., Frank, D. E., Niyo, Y., Ahrens, F. E., Eckersall, P. D., Benson, T. J., & Evans, R. (2003). A scoring index for disease activity in canine inflammatory bowel disease. Journal of Veterinary Internal Medicine, 17(3), 291-297. http://doi.org/10.1111/j.1939-1676.2003.tb02450.x. PMid:12774968.

Kather, S., Grützner, N., Kook, P. H., Dengler, F., & Heilmann, R. M. (2020). Review of cobalamin status and disorders of cobalamin metabolism in dogs. Journal of Veterinary Internal Medicine, 34(1), 13-28. http://doi.org/10.1111/jvim.15638. PMid:31758868.

Kather, S., Kacza, J., Pfannkuche, H., Böttcher, D., Sung, C.-H., Steiner, J. M., Gäbel, G., Dengler, F., & Heilmann, R. M. (2024). Expression of the cobalamin transporters cubam and MRP1 in the canine ileum–Upregulation in chronic inflammatory enteropathy. PLoS One, 19(1), e0296024. http://doi.org/10.1371/journal.pone.0296024. PMid:38206981.

McCann, T. M., Ridyard, A. E., Else, R. W., & Simpson, J. W. (2007). Evaluation of disease activity markers in dogs with idiopathic inflammatory bowel disease. The Journal of Small Animal Practice, 48(11), 620-625. http://doi.org/10.1111/j.1748-5827.2007.00335.x. PMid:17608662.

Otoni, C. C., Heilmann, R. M., García-Sancho, M., Sainz, A., Ackermann, M. R., Suchodolski, J. S., Steiner, J. M., & Jergens, A. E. (2018). Serologic and fecal markers to predict response to induction therapy in dogs with idiopathic inflammatory bowel disease. Journal of Veterinary Internal Medicine, 32(3), 999-1008. http://doi.org/10.1111/jvim.15123. PMid:29624721.

Sacoor, C., Barros, L. M., & Montezinho, L. (2021). What are the potential biomarkers that should be considered in diagnosing and managing canine chronic inflammatory enteropathies? Open Veterinary Journal, 10(4), 412-430. http://doi.org/10.4314/ovj.v10i4.9. PMid:33614437.

Salavati Schmitz, S., Gow, A., Bommer, N., Morrison, L., & Mellanby, R. (2019). Diagnostic features, treatment, and outcome of dogs with inflammatory protein-losing enteropathy. Journal of Veterinary Internal Medicine, 33(5), 2005-2013. http://doi.org/10.1111/jvim.15571. PMid:31381203.

Simpson, K. W., & Jergens, A. E. (2011). Pitfalls and Progress in the Diagnosis and Management of Canine Inflammatory Bowel Disease. The Veterinary Clinics of North America. Small Animal Practice, 41(2), 381-398. http://doi.org/10.1016/j.cvsm.2011.02.003. PMid:21486642.

Tamura, Y., Ohta, H., Kagawa, Y., Osuga, T., Morishita, K., Sasaki, N., & Takiguchi, M. (2019). Plasma amino acid profiles in dogs with inflammatory bowel disease. Journal of Veterinary Internal Medicine, 33(4), 1602-1607. http://doi.org/10.1111/jvim.15525. PMid:31111561.

Thames, B. E., Barr, J. W., Suchodolski, J. S., Steiner, J. M., & Heilmann, R. M. (2019). Prospective evaluation of S100A12 and S100A8/A9 (calprotectin) in dogs with sepsis or the systemic inflammatory response syndrome. Journal of Veterinary Diagnostic Investigation, 31(4), 645-651. http://doi.org/10.1177/1040638719856655. PMid:31170888.

Ullal, T. V., Marks, S. L., Huebner, S. N., Taylor, S. L., & Shelley, C. D. (2023). Association of folate concentrations with clinical signs and laboratory markers of chronic enteropathy in dogs. Journal of Veterinary Internal Medicine, 37(2), 455-464. http://doi.org/10.1111/jvim.16681. PMid:36919188.

Volkmann, M., Steiner, J. M., Fosgate, G. T., Zentek, J., Hartmann, S., & Kohn, B. (2017). Chronic diarrhea in dogs – retrospective study in 136 cases. Journal of Veterinary Internal Medicine, 31(4), 1043-1055. http://doi.org/10.1111/jvim.14739. PMid:28703447.

Wang, Y., Li, C., Wang, W., Wang, J., Li, J., Qian, S., Cai, C., & Liu, Y. (2022). Serum albumin to globulin ratio is associated with the presence and severity of inflammatory bowel disease. Journal of Inflammation Research, 15, 1907-1920. http://doi.org/10.2147/JIR.S347161. PMid:35313674.

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Copyright (c) 2025 Leda Marques de Oliveira-Barros, André Gustavo Alves Holanda, Romy Heilmann, Joerg Manfred Steiner, Genilson Fernandes de Queiroz, José Luiz Catão-Dias, Julia Maria Matera