Fecal Calprotectin Concentrations in Cats with Chronic Enteropathies
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population and Routine Diagnostics
2.2. Sample Collection and Processing
2.3. Fecal Calprotectin Measurement
2.4. Statistical Analysis
3. Results
3.1. Patient Clinical Characteristics
3.2. Clinicopathologic Evaluation
3.3. Histologic Examination
3.4. Treatment Response
3.5. Fecal Calprotectin Concentration
3.6. Association of Patient Characteristics with Fecal Calprotectin Concentrations
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Jergens, A.E. Feline Idiopathic Inflammatory Bowel Disease: What We Know and What Remains to Be Unraveled. J. Feline Med. Surg. 2012, 14, 445–458. [Google Scholar] [CrossRef] [PubMed]
- Richter, K.P. Feline Gastrointestinal Lymphoma. Vet. Clin. N. Am. Small Anim. Pract. 2003, 33, 1083–1098. [Google Scholar] [CrossRef] [PubMed]
- Washabau, R.J.; Day, M.J.; Willard, M.D.; Hall, E.J.; Jergens, A.E.; Mansell, J.; Minami, T.; Bilzer, T.W. Endoscopic, Biopsy, and Histopathologic Guidelines for the Evaluation of Gastrointestinal Inflammation in Companion Animals. J. Vet. Intern. Med. 2010, 24, 10–26. [Google Scholar] [CrossRef] [PubMed]
- Jergens, A.E.; Simpson, K.W. Inflammatory Bowel Disease in Veterinary Medicine. Front. Biosci. 2012, 4, 1404–1419. [Google Scholar] [CrossRef] [PubMed]
- Jergens, A.E.; Crandell, J.M.; Evans, R.; Ackermann, M.; Miles, K.G.; Wang, C. A Clinical Index for Disease Activity in Cats with Chronic Enteropathy. J. Vet. Intern. Med. 2010, 24, 1027–1033. [Google Scholar] [CrossRef]
- Marsilio, S. Differentiating Inflammatory Bowel Disease from Alimentary Lymphoma in Cats: Does It Matter? Vet. Clin. N. Am. Small Anim. Pract. 2021, 51, 93–109. [Google Scholar] [CrossRef]
- Albert, E.J. Inflammatory Bowel Disease: Current Perspectives. Vet. Clin. N. Am. Small Anim. Pract. 1999, 29, 501–521. [Google Scholar] [CrossRef]
- Jergens, A.E.; Heilmann, R.M. Canine Chronic Enteropathy-Current State-of-the-Art and Emerging Concepts. Front. Vet. Sci. 2022, 9, 923013. [Google Scholar] [CrossRef]
- Moore, P.F.; Woo, J.C.; Vernau, W.; Kosten, S.; Graham, P.S. Characterization of Feline T Cell Receptor Gamma (TCRG) Variable Region Genes for the Molecular Diagnosis of Feline Intestinal T Cell Lymphoma. Vet. Immunol. Immunopathol. 2005, 106, 167–178. [Google Scholar] [CrossRef]
- Moore, P.F.; Rodriguez-Bertos, A.; Kass, P.H. Feline Gastrointestinal Lymphoma: Mucosal Architecture, Immunophenotype, and Molecular Clonality. Vet. Pathol. 2012, 49, 658–668. [Google Scholar] [CrossRef] [Green Version]
- Marsilio, S. Feline Chronic Enteropathy. J. Small Anim. Pract. 2021, 62, 409–419. [Google Scholar] [CrossRef]
- Barrs, V.R.; Beatty, J.A. Feline Alimentary Lymphoma: 2. Further Diagnostics, Therapy and Prognosis. J. Feline Med. Surg. 2012, 14, 191–201. [Google Scholar] [CrossRef]
- Lingard, A.E.; Briscoe, K.; Beatty, J.A.; Moore, A.S.; Crowley, A.M.; Krockenberger, M.; Churcher, R.K.; Canfield, P.J.; Barrs, V.R. Low-Grade Alimentary Lymphoma: Clinicopathological Findings and Response to Treatment in 17 Cases. J. Feline Med. Surg. 2009, 11, 692–700. [Google Scholar] [CrossRef]
- Kiselow, M.A.; Rassnick, K.M.; Mcdonough, S.P.; Goldstein, R.E.; Simpson, K.W.; Weinkle, T.K.; Erb, H.N. Outcome of Cats with Low-Grade Lymphocytic Lymphoma: 41 Cases (1995–2005). J. Am. Vet. Med. Assoc. 2008, 232, 405–410. [Google Scholar] [CrossRef] [Green Version]
- Marsilio, S.; Pilla, R.; Sarawichitr, B.; Chow, B.; Hill, S.L.; Ackermann, M.R.; Estep, J.S.; Lidbury, J.A.; Steiner, J.M.; Suchodolski, J.S. Characterization of the Fecal Microbiome in Cats with Inflammatory Bowel Disease or Alimentary Small Cell Lymphoma. Sci. Rep. 2019, 9, 19208. [Google Scholar] [CrossRef] [Green Version]
- Norsworthy, G.D.; Estep, J.S.; Hollinger, C.; Steiner, J.M.; Lavallee, J.O.; Gassler, L.N.; Restine, L.M.; Kiupel, M. Prevalence and Underlying Causes of Histologic Abnormalities in Cats Suspected to Have Chronic Small Bowel Disease: 300 Cases (2008–2013). J. Am. Vet. Med. Assoc. 2015, 247, 629–635. [Google Scholar] [CrossRef]
- Burke, K.F.; Broussard, J.D.; Ruaux, C.G.; Suchodolski, J.S.; Williams, D.A.; Steiner, J.M. Evaluation of Fecal A1-Proteinase Inhibitor Concentrations in Cats with Idiopathic Inflammatory Bowel Disease and Cats with Gastrointestinal Neoplasia. Vet. J. 2013, 196, 189–196. [Google Scholar] [CrossRef]
- Waly, N.E.; Gruffydd-Jones, T.J.; Stokes, C.R.; Day, M.J. Immunohistochemical Diagnosis of Alimentary Lymphomas and Severe Intestinal Inflammation in Cats. J. Comp. Pathol. 2005, 133, 253–260. [Google Scholar] [CrossRef]
- Reed, N.; Gunn-Moore, D.; Simpson, K. Cobalamin, Folate and Inorganic Phosphate Abnormalities in Ill Cats. J. Feline Med. Surg. 2007, 9, 278–288. [Google Scholar] [CrossRef]
- Riggers, D.S.; Gurtner, C.; Protschka, M.; Böttcher, D.; Von Bomhard, W.; Alber, G.; Winter, K.; Steiner, J.M.; Heilmann, R.M. Intestinal S100/Calgranulin Expression in Cats with Chronic Inflammatory Enteropathy and Intestinal Lymphoma. Animals 2022, 12, 2044. [Google Scholar] [CrossRef]
- Heilmann, R.M.; Allenspach, K. Pattern-Recognition Receptors: Signaling Pathways and Dysregulation in Canine Chronic Enteropathies—Brief Review. J. Vet. Diagn. Investig. 2017, 29, 781–787. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heilmann, R.M.; Berghoff, N.; Mansell, J.; Grützner, N.; Parnell, N.K.; Gurtner, C.; Suchodolski, J.S.; Steiner, J.M. Association of Fecal Calprotectin Concentrations with Disease Severity, Response to Treatment, and Other Biomarkers in Dogs with Chronic Inflammatory Enteropathies. J. Vet. Intern. Med. 2018, 32, 679–692. [Google Scholar] [CrossRef] [PubMed]
- Heilmann, R.M.; Grellet, A.; Allenspach, K.; Lecoindre, P.; Day, M.J.; Priestnall, S.L.; Toresson, L.; Procoli, F.; Grützner, N.; Suchodolski, J.S.; et al. Association between Fecal S100A12 Concentration and Histologic, Endoscopic, and Clinical Disease Severity in Dogs with Idiopathic Inflammatory Bowel Disease. Vet. Immunol. Immunopathol. 2014, 158, 156–166. [Google Scholar] [CrossRef]
- Otoni, C.C.; Heilmann, R.M.; García-Sancho, M.; Sainz, A.; Ackermann, M.R.; Suchodolski, J.S.; Steiner, J.M.; Jergens, A.E. Serologic and Fecal Markers to Predict Response to Induction Therapy in Dogs with Idiopathic Inflammatory Bowel Disease. J. Vet. Intern. Med. 2018, 32, 999–1008. [Google Scholar] [CrossRef] [PubMed]
- Heilmann, R.M.; Steiner, J.M. Clinical Utility of Currently Available Biomarkers in Inflammatory Enteropathies of Dogs. J. Vet. Intern. Med. 2018, 32, 1495–1508. [Google Scholar] [CrossRef] [PubMed]
- Goyette, J.; Geczy, C.L. Inflammation-Associated S100 Proteins: New Mechanisms That Regulate Function. Amino Acids 2011, 41, 821–842. [Google Scholar] [CrossRef]
- Foell, D.; Frosch, M.; Sorg, C.; Roth, J. Phagocyte-Specific Calcium-Binding S100 Proteins as Clinical Laboratory Markers of Inflammation. Clin. Chim. Acta 2004, 344, 37–51. [Google Scholar] [CrossRef]
- Heilmann, R.M.; Nestler, J.; Schwarz, J.; Grützner, N.; Ambrus, A.; Seeger, J.; Suchodolski, J.S.; Steiner, J.M.; Gurtner, C. Mucosal Expression of S100A12 (Calgranulin C) and S100A8/A9 (Calprotectin) and Correlation with Serum and Fecal Concentrations in Dogs with Chronic Inflammatory Enteropathy. Vet. Immunol. Immunopathol. 2019, 211, 64–74. [Google Scholar] [CrossRef]
- Vogl, T.; Tenbrock, K.; Ludwig, S.; Leukert, N.; Ehrhardt, C.; Van Zoelen, M.A.D.; Nacken, W.; Foell, D.; Van Der Poll, T.; Sorg, C.; et al. Mrp8 and Mrp14 Are Endogenous Activators of Toll-like Receptor 4, Promoting Lethal, Endotoxin-Induced Shock. Nat. Med. 2007, 13, 1042–1049. [Google Scholar] [CrossRef]
- Abej, E.; El-Matary, W.; Singh, H.; Bernstein, C.N. The Utility of Fecal Calprotectin in the Real-World Clinical Care of Patients with Inflammatory Bowel Disease. Can. J. Gastroenterol. Hepatol. 2016, 2016, 2483261. [Google Scholar] [CrossRef] [Green Version]
- Grellet, A.; Heilmann, R.M.; Lecoindre, P.; Feugier, A.; Day, M.J.; Peeters, D.; Freiche, V.; Hernandez, J.; Grandjean, D.; Suchodolski, J.S.; et al. Fecal Calprotectin Concentrations in Adult Dogs with Chronic Diarrhea. Am. J. Vet. Res. 2013, 74, 706–711. [Google Scholar] [CrossRef]
- Heilmann, R.M.; Grützner, N.; Handl, S.; Suchodolski, J.S.; Steiner, J.M. Preanalytical Validation of an In-House Radioimmunoassay for Measuring Calprotectin in Feline Specimens. Vet. Clin. Pathol. 2018, 47, 100–107. [Google Scholar] [CrossRef]
- Heilmann, R.M.; Ruaux, C.G.; Grützner, N.; Cranford, S.M.; Bridges, C.S.; Steiner, J.M. Biological Variation of Serum Canine Calprotectin Concentrations as Measured by ELISA in Healthy Dogs. Vet. J. 2019, 247, 61–64. [Google Scholar] [CrossRef]
- Røseth, A.G.; Aadland, E.; Grzyb, K. Normalization of Faecal Calprotectin: A Predictor of Mucosal Healing in Patients with Inflammatory Bowel Disease. Scand. J. Gastroenterol. 2004, 39, 1017–1020. [Google Scholar] [CrossRef]
- Røseth, A.G.; Fagerhol, M.K.; Aadland, E.; Schjønsby, H. Assessment of the Neutrophil Dominating Protein Calprotectin in Feces. A Methodologic Study. Scand. J. Gastroenterol. 1992, 27, 793–798. [Google Scholar] [CrossRef]
- De Sloovere, M.M.W.; De Smet, D.; Baert, F.J.; Debrabandere, J.; Vanpoucke, H.J.M. Analytical and Diagnostic Performance of Two Automated Fecal Calprotectin Immunoassays for Detection of Inflammatory Bowel Disease. Clin. Chem. Lab. Med. 2017, 55, 1435–1446. [Google Scholar] [CrossRef]
- Tibble, J.; Teahon, K.; Thjodleifsson, B.; Roseth, A.; Sigthorsson, G.; Bridger, S.; Foster, R.; Sherwood, R.; Fagerhol, M.; Bjarnason, I. A Simple Method for Assessing Intestinal Inflammation in Crohn’s Disease. Gut 2000, 47, 506–513. [Google Scholar] [CrossRef] [Green Version]
- Tibble, J.A.; Sigthorsson, G.; Bridger, S.; Fagerhol, M.K.; Bjarnason, I. Surrogate Markers of Intestinal Inflammation Are Predictive of Relapse in Patients with Inflammatory Bowel Disease. Gastroenterology 2000, 119, 15–22. [Google Scholar] [CrossRef]
- Truar, K.; Nestler, J.; Schwarz, J.; Grützner, N.; Gabris, C.; Kock, K. Feasibility of Measuring Fecal Calprotectin Concentrations in Dogs and Cats by the Fcal® Turbo Immunoassay. Abstract. J. Vet. Intern. Med. 2018, 32, 580. [Google Scholar]
- Dandrieux, J.R.S. Inflammatory Bowel Disease versus Chronic Enteropathy in Dogs: Are They One and the Same? J. Small Anim. Pract. 2016, 57, 589–599. [Google Scholar] [CrossRef]
- Heilmann, R.M.; Lanerie, D.J.; Ruaux, C.G.; Grützner, N.; Suchodolski, J.S.; Steiner, J.M. Development and Analytic Validation of an Immunoassay for the Quantification of Canine S100A12 in Serum and Fecal Samples and Its Biological Variability in Serum from Healthy Dogs. Vet. Immunol. Immunopathol. 2011, 144, 200–209. [Google Scholar] [CrossRef] [PubMed]
- Bühlmann Laboratories AG. BÜHLMANN Fcal® Turbo Calprotectin Turbidimetric Assay for Professional Use: Reagent Kit. [Cited 28 May 2019]. Available online: https://www.buhlmannlabs.ch/wp-content/uploads/2015/01/B-KCAL-RSET_CE0123_IFU_VA4_2022-02-28_EN.pdf (accessed on 27 June 2023).
- Enderle, L.L.; Köller, G.; Heilmann, R.M. Verification of the Fcal Turbo Immunoturbidimetric Assay for Measurement of the Fecal Calprotectin Concentration in Dogs and Cats. J. Vet. Diagn. Investig. 2022, 34, 813–824. [Google Scholar] [CrossRef] [PubMed]
- Hsu, K.; Passey, R.J.; Endoh, Y.; Rahimi, F.; Youssef, P.; Yen, T.; Geczy, C.L. Regulation of S100A8 by Glucocorticoids. J. Immunol. 2005, 174, 2318–2326. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guttin, T.; Walsh, A.; Durham, A.C.; Reetz, J.A.; Brown, D.C.; Rondeau, M.P. Ability of Ultrasonography to Predict the Presence and Location of Histologic Lesions in the Small Intestine of Cats. J. Vet. Intern. Med. 2019, 33, 1278–1285. [Google Scholar] [CrossRef]
- Freiche, V.; Fages, J.; Paulin, M.V.; Bruneau, J.; Couronné, L.; German, A.J.; Penninck, D.; Hermine, O. Clinical, Laboratory and Ultrasonographic Findings Differentiating Low-Grade Intestinal T-Cell Lymphoma from Lymphoplasmacytic Enteritis in Cats. J. Vet. Intern. Med. 2021, 35, 2685–2696. [Google Scholar] [CrossRef]
- Cavett, C.L.; Tonero, M.; Marks, S.L.; Winston, J.A.; Gilor, C.; Rudinsky, A.J. Consistency of Faecal Scoring Using Two Canine Faecal Scoring Systems. J. Small Anim. Pract. 2021, 62, 167–173. [Google Scholar] [CrossRef]
- Day, M.J.; Bilzer, T.; Mansell, J.; Wilcock, B.; Hall, E.J.; Jergens, A.; Minami, T.; Willard, M.; Washabau, R. 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. J. Comp. Pathol. 2008, 138 (Suppl. S1), S1–S43. [Google Scholar] [CrossRef]
- Heilmann, R.M.; Guard, M.M.; Steiner, J.M.; Suchodolski, J.S.; Unterer, S. Fecal Markers of Inflammation, Protein Loss, and Microbial Changes in Dogs with the Acute Hemorrhagic Diarrhea Syndrome (AHDS). J. Vet. Emerg. Crit. Care 2017, 27, 586–589. [Google Scholar] [CrossRef]
- Ross, F.A.; Park, J.H.; Mansouri, D.; Little, C.; Di Rollo, D.G.; Combet, E.; Van Wyk, H.; Horgan, P.G.; Mcmillan, D.C.; Roxburgh, C.S.D. The Role of Faecal Calprotectin in the Identification of Colorectal Neoplasia in Patients Attending for Screening Colonoscopy. Color. Dis. 2022, 24, 188–196. [Google Scholar] [CrossRef]
- Kan, Y.M.; Chu, S.Y.; Loo, C.K. Diagnostic Accuracy of Fecal Calprotectin in Predicting Significant Gastrointestinal Diseases. JGH Open 2021, 5, 647–652. [Google Scholar] [CrossRef]
- Freiche, V.; Paulin, M.V.; Cordonnier, N.; Huet, H.; Turba, M.-E.; Macintyre, E.; Molina, T.-J.; Hermine, O.; Couronné, L.; Bruneau, J. Histopathologic, Phenotypic, and Molecular Criteria to Discriminate Low-Grade Intestinal T-Cell Lymphoma in Cats from Lymphoplasmacytic Enteritis. J. Vet. Intern. Med. 2021, 35, 2673–2684. [Google Scholar] [CrossRef]
- Marsilio, S.; Ackermann, M.R.; Lidbury, J.A.; Suchodolski, J.S.; Steiner, J.M. Results of Histopathology, Immunohistochemistry, and Molecular Clonality Testing of Small Intestinal Biopsy Specimens from Clinically Healthy Client-Owned Cats. J. Vet. Intern. Med. 2019, 33, 551–558. [Google Scholar] [CrossRef] [Green Version]
- Welter, J.; Duckova, T.; Groiss, S.; Wolfesberger, B.; Fuchs-Baumgartinger, A.; Rütgen, B.C.; Hammer, S.E. Revisiting Lymphocyte Clonality Testing in Feline B-Cell Lymphoma. Vet. Immunol. Immunopathol. 2021, 242, 110350. [Google Scholar] [CrossRef]
- Anindita, B.; Sugihartono, T.; Miftahussurur, M.; Maimunah, U.; Nusi, I.A.; Setiawan, P.B.; Purbayu, H.; Kholili, U.; Widodo, B.; Thamrin, H.; et al. High Levels of Fecal Calprotectin and C-Reactive Protein in Patients with Colitis. J. Med. Life 2023, 16, 48–51. [Google Scholar] [CrossRef]
- Conroy, S.; Hale, M.F.; Cross, S.S.; Swallow, K.; Sidhu, R.H.; Sargur, R.; Lobo, A.J. Unrestricted Faecal Calprotectin Testing Performs Poorly in the Diagnosis of Inflammatory Bowel Disease in Patients in Primary Care. J. Clin. Pathol. 2018, 71, 316–322. [Google Scholar] [CrossRef]
- Carrasco-Labra, A.; Lytvyn, L.; Falck-Ytter, Y.; Surawicz, C.M.; Chey, W.D. AGA Technical Review on the Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D). Gastroenterology 2019, 157, 859–880. [Google Scholar] [CrossRef]
- Marsilio, S.; Kleinschmidt, S.; Nolte, I.; Hewicker-Trautwein, M. Immunohistochemical and Morphometric Analysis of Intestinal Full-Thickness Biopsy Samples from Cats with Lymphoplasmacytic Inflammatory Bowel Disease. J. Comp. Pathol. 2014, 150, 416–423. [Google Scholar] [CrossRef]
- D’Amico, F.; Nancey, S.; Danese, S.; Peyrin-Biroulet, L. A Practical Guide for Faecal Calprotectin Measurement: Myths and Realities. J. Crohn’s Colitis 2021, 15, 152–161. [Google Scholar] [CrossRef]
- Malvão, L.D.R.; Madi, K.; Esberard, B.C.; De Amorim, R.F.; Silva, K.D.S.; Farias E Silva, K.; De Souza, H.S.P.; Carvalho, A.T.P. Fecal Calprotectin as a Noninvasive Test to Predict Deep Remission in Patients with Ulcerative Colitis. Medicine 2021, 100, e24058. [Google Scholar] [CrossRef]
- Kawashima, K.; Oshima, N.; Kishimoto, K.; Kataoka, M.; Fukunaga, M.; Kotani, S.; Sonoyama, H.; Oka, A.; Mishima, Y.; Kazumori, H.; et al. Low Fecal Calprotectin Predicts Histological Healing in Patients with Ulcerative Colitis with Endoscopic Remission and Leads to Prolonged Clinical Remission. Inflamm. Bowel Dis. 2023, 29, 359–366. [Google Scholar] [CrossRef]
- Jergens, A.E.; Schreiner, C.A.; Frank, D.E.; Niyo, Y.; Ahrens, F.E.; Eckersall, P.D.; Benson, T.J.; Evans, R. A Scoring Index for Disease Activity in Canine Inflammatory Bowel Disease. J. Vet. Intern. Med. 2003, 17, 291–297. [Google Scholar] [CrossRef] [PubMed]
- Allenspach, K.; Wieland, B.; Gröne, A.; Gaschen, F. Chronic Enteropathies in Dogs: Evaluation of Risk Factors for Negative Outcome. J. Vet. Intern. Med. 2007, 21, 700. [Google Scholar] [CrossRef]
- Dandrieux, J.; Freiche, V. Challenges in Differentiating Chronic Enteropathy from Low-Grade Gastrointestinal T-Cell Lymphoma in Cats. Adv. Small Anim. Care 2022, 3, 121–131. [Google Scholar] [CrossRef]
- Daniaux, L.A.; Laurenson, M.P.; Marks, S.L.; Moore, P.F.; Taylor, S.L.; Chen, R.X.; Zwingenberger, A.L. Ultrasonographic Thickening of the Muscularis Propria in Feline Small Intestinal Small Cell T-Cell Lymphoma and Inflammatory Bowel Disease. J. Feline Med. Surg. 2014, 16, 89–98. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zwingenberger, A.L.; Marks, S.L.; Baker, T.W.; Moore, P.F. Ultrasonographic Evaluation of the Muscularis Propria in Cats with Diffuse Small Intestinal Lymphoma or Inflammatory Bowel Disease. J. Vet. Intern. Med. 2010, 24, 289–292. [Google Scholar] [CrossRef] [PubMed]
- Brown, C.A.; Elliott, J.; Schmiedt, C.W.; Brown, S.A. Chronic Kidney Disease in Aged Cats: Clinical Features, Morphology, and Proposed Pathogeneses. Vet. Pathol. 2016, 53, 309–326. [Google Scholar] [CrossRef]
- Griffin, J.F. Stress and Immunity: A Unifying Concept. Vet. Immunol. Immunopathol. 1989, 20, 263–312. [Google Scholar] [CrossRef]
- Tanaka, A.; Wagner, D.C.; Kass, P.H.; Hurley, K.F. Associations among Weight Loss, Stress, and Upper Respiratory Tract Infection in Shelter Cats. J. Am. Vet. Med. Assoc. 2012, 240, 570–576. [Google Scholar] [CrossRef]
- Buffington, C.A.T. Idiopathic Cystitis in Domestic Cats—Beyond the Lower Urinary Tract. J. Vet. Intern. Med. 2011, 25, 784–796. [Google Scholar] [CrossRef] [Green Version]
- Cameron, M.E.; Casey, R.A.; Bradshaw, J.W.S.; Waran, N.K.; Gunn-Moore, D.A. A Study of Environmental and Behavioural Factors That May Be Associated with Feline Idiopathic Cystitis. J. Small Anim. Pract. 2004, 45, 144–147. [Google Scholar] [CrossRef]
- Amat, M.; Camps, T.; Manteca, X. Stress in Owned Cats: Behavioural Changes and Welfare Implications. J. Feline Med. Surg. 2016, 18, 577–586. [Google Scholar] [CrossRef]
- Enck, P.; Holtmann, G. Stress and Gastrointestinal Motility in Animals: A Review of the Literature. Neurogastroenterol. Motil. 1992, 4, 83–90. [Google Scholar] [CrossRef]
- Stella, J.L.; Lord, L.K.; Buffington, C.A.T. Sickness Behaviors in Response to Unusual External Events in Healthy Cats and Cats with Feline Interstitial Cystitis. J. Am. Vet. Med. Assoc. 2011, 238, 67–73. [Google Scholar] [CrossRef] [Green Version]
- Lambert, G.P. Stress-Induced Gastrointestinal Barrier Dysfunction and Its Inflammatory Effects. J. Anim. Sci. 2009, 87, e101–e108. [Google Scholar] [CrossRef] [Green Version]
- Kathrani, A. Dietary and Nutritional Approaches to the Management of Chronic Enteropathy in Dogs and Cats. Vet. Clin. N. Am. Small Anim. Pract. 2021, 51, 123–136. [Google Scholar] [CrossRef]
- Miyaji, K.; Kato, M.; Ohtani, N.; Ohta, M. Experimental Verification of the Effects on Normal Domestic Cats by Feeding Prescription Diet for Decreasing Stress. J. Appl. Anim. Welf. Sci. JAAWS 2015, 18, 355–362. [Google Scholar] [CrossRef]
- Landsberg, G.; Milgram, B.; Mougeot, I.; Kelly, S.; De Rivera, C. Therapeutic Effects of an Alpha-Casozepine and L-Tryptophan Supplemented Diet on Fear and Anxiety in the Cat. J. Feline Med. Surg. 2017, 19, 594–602. [Google Scholar] [CrossRef]
- Hashimoto, T.; Perlot, T.; Rehman, A.; Trichereau, J.; Ishiguro, H.; Paolino, M.; Sigl, V.; Hanada, T.; Hanada, R.; Lipinski, S.; et al. ACE2 Links Amino Acid Malnutrition to Microbial Ecology and Intestinal Inflammation. Nature 2012, 487, 477–481. [Google Scholar] [CrossRef]
- Nikolaus, S.; Schulte, B.; Al-Massad, N.; Thieme, F.; Schulte, D.M.; Bethge, J.; Rehman, A.; Tran, F.; Aden, K.; Häsler, R.; et al. Increased Tryptophan Metabolism Is Associated with Activity of Inflammatory Bowel Diseases. Gastroenterology 2017, 153, 1504–1516.e2. [Google Scholar] [CrossRef] [Green Version]
- Gupta, N.K.; Thaker, A.I.; Kanuri, N.; Riehl, T.E.; Rowley, C.W.; Stenson, W.F.; Ciorba, M.A. Serum Analysis of Tryptophan Catabolism Pathway: Correlation with Crohn’s Disease Activity. Inflamm. Bowel Dis. 2012, 18, 1214–1220. [Google Scholar] [CrossRef] [Green Version]
- Beeken, W.L. Serum Tryptophan in Crohn’s Disease. Scand. J. Gastroenterol. 1976, 11, 735–740. [Google Scholar] [CrossRef] [PubMed]
- Kathrani, A.; Allenspach, K.; Fascetti, A.J.; Larsen, J.A.; Hall, E.J. Alterations in Serum Amino Acid Concentrations in Dogs with Protein-Losing Enteropathy. J. Vet. Intern. Med. 2018, 32, 1026–1032. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, C.J.; Kovacs-Nolan, J.A.; Yang, C.; Archbold, T.; Fan, M.Z.; Mine, Y. L-Tryptophan Exhibits Therapeutic Function in a Porcine Model of Dextran Sodium Sulfate (DSS)-Induced Colitis. J. Nutr. Biochem. 2010, 21, 468–475. [Google Scholar] [CrossRef]
- Bettenworth, D.; Nowacki, T.M.; Ross, M.; Kyme, P.; Schwammbach, D.; Kerstiens, L.; Thoennissen, G.B.; Bokemeyer, C.; Hengst, K.; Berdel, W.E.; et al. Nicotinamide Treatment Ameliorates the Course of Experimental Colitis Mediated by Enhanced Neutrophil-Specific Antibacterial Clearance. Mol. Nutr. Food Res. 2014, 58, 1474–1490. [Google Scholar] [CrossRef] [PubMed]
- Lim, B.O. Coriolus Versicolor Suppresses Inflammatory Bowel Disease by Inhibiting the Expression of STAT1 and STAT6 Associated with IFN-Γ and IL-4 Expression. Phytother. Res. PTR 2011, 25, 1257–1261. [Google Scholar] [CrossRef]
Patient Characteristic | CIE | SCL | Disease Controls | Healthy Controls | p-Value |
---|---|---|---|---|---|
Age in years, median (IQR) | 9.0 (4.8–11.3) A | 13.0 (11.0–14.0) B | 9.0 (2.0–13.0) A,C | 5.5 (2.0–10.0) C | 0.0004 |
Sex, male (neutered)/female (spayed) | 24 (22)/10 (10) | 10 (8)/7 (7) | 9 (9)/7 (5) | 19 (18)/13 (12) | 0.6887 |
Body weight in kg, median (IQR) | 4.4 (3.6–5.7) * | 5.5 (3.8–6.0) | 4.0 (3.3–4.9) † | 4.5 (4.2–5.5) ‡ | 0.2099 |
BCS, median (IQR) | 5.0 (3.5–5.5) $ | 6.0 (4.0–7.0) § | 5.5 (3.5–7.5) ¶ | 5.5 (4.5–5.5) $ | 0.4784 |
Breed, n (%) - Domestic (European) Shorthair - other breeds | 24 (71%) 10 (29%) | 14 (82%) 3 (18%) | 9 (56%) 7 (44%) | 26 (81%) 6 (19%) | 0.2455 |
Negative retrovirus (FeLV/FIV) status | 8 (100%) ** | 2 (100%) †† | 5 (100%) ‡‡ | – | – |
Clinical signs present in months, median (IQR) | 8.0 (1.0–24.0) § | 0.6 (0.2–1.0) †† | 1.0 (1.0–12.0) $$ | – | 0.1413 |
Minimum survival time in months, median (IQR) | 3.0 (3.0–12.0) §§,A,B | 3.0 (3.0–3.0) ¶¶,A | 9.0 (3.5–18.0) †,B | – | 0.0362 |
Number of sites biopsied, median (IQR) | 4 (4) # | 2 (2) ¶¶ | 3 (2–4) †† | – | |
Clinical parameters | |||||
FCEAI score, median (IQR) - severity of reduced activity - severity of vomiting - severity of diarrhea - severity of weight loss - severity of hyporexia | 6 (3–9) A 1 (0–2) A 1 (0–2) A 1 (0–2) A 1 (0–1.5) A 1 (0–2) A | 10 (7–11.5) B 1 (0–2) A 2 (1–3) B 2 (1–3) B 1 (0.5–2) A 1 (0.5–2.5) A | 5.5 (2.5–7) A 1 (0–2) §,A 1 (0–2) §,A 1.5 (0–2) A 0 (0–2) §,A 0 (0–2) §,A | 0 (0) C 0 (0) B 0 (0) C 0 (0) C 0 (0) B 0 (0) B | <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 |
Presence of endoscopic lesions, n (%) - stomach ! - duodenum/jejunum ! - ileum ** - colon ** | 27 (100%) #
| 17 (100%)
| 2 (100%) ††
| – | – 0.9742 0.6187 0.1372 0.3219 |
Presence of dermatological signs, n (%) $$ | 3/8 (38%) | 0/2 (0%) | 3/4 (75%) | – | 0.2112 |
Stress association of clinical signs, n (%) ¶¶ | 6/8 (75%) A,B | 0/2 (0%) A | 7/7 (100%) B | – | 0.0084 |
Clinicopathologic parameters | |||||
Serum cobalamin in ng/L, median (IQR) | 914 (430–1001) A,& | 318 (178–637) B | 355 (197–963) A,B,** | – | 0.0054 |
Hypocobalaminemia, n (%) | 4/30 (13%) & | 7/17 (42%) | 2/8 (25%) ** | – | 0.0717 |
Serum folate in µg/L, median (IQR) | 18.1 (13.0–22.8) # | 16.3 (8.4–30.8) ^ | 14.1 (11.9–29.3) ** | – | 0.7887 |
Hypofolatemia, n (%) | 3/28 (11%) | 3/16 (19%) | 0/8 (0%) | – | 0.2615 |
Hyperfolatemia, n (%) | 5/28 (18%) | 5/16 (31%) | 2/8 (25%) | – | 0.5967 |
Serum total protein in g/L, median (IQR) | 73 (66–79) ß | 72 (62–74) § | 75 (70–81) § | – | 0.2925 |
Hypoproteinemia, n (%) | 2/32 (6%) | 3/15 (20%) | 0/12 (0%) | – | 0.0950 |
Hyperproteinemia, n (%) | 3/32 (9%) | 1/15 (7%) | 4/12 (33%) | – | 0.1167 |
Serum albumin in g/L, median (IQR) | 36 (33–40) A,& | 36 (30.5–40) A,^ | 31 (26.5–34.5) B,$$ | – | 0.0222 |
Hypoalbuminemia, n (%) | 4/30 (13%) | 2/16 (13%) | 2/14 (14%) | – | 0.9898 |
Serum globulin in g/L, median (IQR) | 33.5 (31–43.5) A,& | 32 (30–36) A,§ | 42 (36.5–51) B,% | – | 0.0181 |
Hyperglobulinemia, n (%) | 10/30 (33%) A,B | 3/15 (20%) A | 8/12 (67%) B | – | 0.0379 |
Serum total calcium in mmol/L, median (IQR) | 2.50 (2.40–2.63) # | 2.54 (2.33–2.69) ^ | 2.50 (2.40–2.60) ## | – | 0.8709 |
Total hypocalcemia, n (%) | 0/27 (0%) | 2/16 (13%) | 1/7 (14%) | – | 0.0864 |
Serum BUN in mmol/L, median (IQR) | 18 (8–22.5) A,!! | 23 (19.5–30) B,^ | 9 (7.5–12.5) C,&& | – | 0.0001 |
Serum BUN increase, n (%) | 18/29 (62%) A | 15/16 (94%) B | 4/13 (31%) A | – | 0.0010 |
Serum phosphorus in mmol/L, median (IQR) | 0.47 (0.34–0.56) # | 0.52 (0.44–0.54) ^ | 0.61 (0.45–0.65) ## | – | 0.1108 |
Hypophosphatemia, n (%) | 2/28 (7%) | 0/16 (0%) | 0/7 (0%) | – | 0.2915 |
Serum ALT activity in U/L, median (IQR) | 59 (37–88) & | 68 (52–121) ^ | 65 (47–156) ^^ | – | 0.3389 |
Increased serum ALT activity, n (%) | 8/31 (26%) | 7/16 (44%) | 2/9 (22%) | – | 0.3898 |
Serum ALP activity in U/L, median (IQR) | 32 (25–48) §§ | 32 (26–51) ^ | 56 (29–70) && | – | 0.4767 |
Increased serum ALP activity, n (%) | 5/32 (16%) | 2/16 (13%) | 5/14 (36%) | – | 0.2368 |
Serum tT4 in nmol/L, median (IQR) | 24.5 (20.8–34.3) A,ßß | 34.5 (29.5–37.6) B,&& | 43.2 (21.9–50.2) A,B,## | – | 0.0145 |
Serum Spec fPL in μg/L, median (IQR) | 2.0 (1.4–4.2) & | 2.7 (2.5–3.3) ¶¶ | 1.7 (1.4–4.2) ** | 0.0752 | |
Increased serum Spec fPL, n (%) | 8/31 (26%) | 4/17 (24%) | 2/8 (25%) | – | 0.2368 |
Serum fTLI in μg/L, median (IQR) | 21.4 (15.7–35.3) A,%% | 60.5 (36.3–69.8) B,$$ | 45.7 (31.6–102.4) A,B,### | – | 0.0024 |
Serum fructosamine in μmol/L, median (IQR) | 225 (203–277) ^^ | – | 254 (232–286) ¶ | – | 0.5161 |
Sonographic abnormalities | |||||
Increased gastrointestinal wall thickness, n (%) !!! | 12/13 (92%) A | 2/2 (100%) A | 4/11 (36%) B | – | 0.0049 |
Thickened tunica muscularis layer, n (%) !!! | 7/13 (54%) | 1/2 (50%) | 4/11 (36%) | – | 0.6867 |
Loss of gastrointestinal wall layering, n (%) !!! | 3/13 (23%) | 1/2 (50%) | 0/11 (0%) | – | 0.0637 |
Enlarged regional lymph nodes, n (%) !!! | 11/13 (85%) | 1/2 (50%) | 5/11 (46%) | – | 0.1081 |
Evidence of free abdominal fluid, n (%) !!! | 5/13 (39%) | 0/2 (0%) | 3/11 (27%) | – | 0.3902 |
Fecal biomarker of inflammation | |||||
Fecal calprotectin in μg/g, median (IQR) | 42 (17–232) A | 50 (21–181) A | 145 (5–351) A | 3 (3) B | <0.0001 |
Parameter | Spearman ρ Correlation Coefficient (p-Value) | ||
---|---|---|---|
Correlated with | fCal Concentration | FCEAI Score | |
Clinical criteria | |||
FCEAI score | 0.21 (0.2546) | - | |
Serum protein concentrations | |||
Serum albumin concentration | −0.45 (0.0165) | −0.23 (0.2135) | |
Serum globulin concentration | 0.48 (0.0104) | 0.01 (0.9773) | |
Serum functional biomarker | |||
Serum cobalamin concentration | −0.40 (0.0335) | −0.49 (0.0058) | |
Histologic criteria | |||
Histologic lesions (composite score) ¶ | 0.37 (0.0789) | 0.09 (0.6777) | |
Morphologic criteria ¶ | 0.30 (0.1540) | 0.21 (0.3262) | |
Inflammatory criteria ¶ | 0.23 (0.2949) | 0.01 (0.9483) | |
Duodenum/jejunum (composite score) | 0.44 (0.0305) | 0.39 (0.0526) | |
Morphologic criteria (sum) | 0.29 (0.1761) | 0.17 (0.4118) | |
| 0.62 (0.0011) | 0.19 (0.3611) | |
| 0.28 (0.1824) | 0.40 (0.0486) | |
| −0.71 (0.0001) | 0.01 (0.9798) | |
| 0.11 (0.6232) | −0.03 (0.8924) | |
| 0.43 (0.0366) | 0.11 (0.5949) | |
Inflammatory criteria (sum) | 0.35 (0.0913) | 0.39 (0.0560) | |
| 0.22 (0.3141) | −0.02 (0.9184) | |
| 0.20 (0.3416) | 0.44 (0.0304) | |
| n/a | n/a | |
| 0.20 (0.3446) | 0.19 (0.3713) | |
| 0.23 (0.2874) | 0.33 (0.1097) | |
Ileum (composite score) | 0.35 (0.1161) | 0.23 (0.2993) | |
Morphologic criteria (sum) | 0.32 (0.1570) | 0.41 (0.0618) | |
| 0.34 (0.1374) | 0.14 (0.5359) | |
| 0.52 (0.0149) | 0.42 (0.0527) | |
| 0.37 (0.0983) | 0.14 (0.5385) | |
| n/a | n/a | |
| −0.03 (0.8854) | 0.47 (0.0246) | |
Inflammatory criteria (sum) | 0.27 (0.2445) | −0.03 (0.9133) | |
| −0.14 (0.5444) | −0.23 (0.2978) | |
| 0.32 (0.1541) | 0.01 (0.9524) | |
| n/a | n/a | |
| 0.26 (0.2450) | 0.34 (0.1125) | |
| 0.26 (0.2450) | 0.34 (0.1125) | |
Colon (composite score) | −0.11 (0.6280) | −0.22 (0.3080) | |
Morphologic criteria (sum) | −0.18 (0.4085) | −0.17 (0.4183) | |
| 0.36 (0.0823) | −0.11 (0.6174) | |
| −0.38 (0.0731) | −0.24 (0.2511) | |
| −0.13 (0.5266) | −0.14 (0.5002) | |
| −0.16 (0.4575) | 0.09 (0.6746) | |
Inflammatory criteria (sum) | 0.18 (0.3954) | −0.16 (0.4399) | |
| 0.28 (0.1807) | 0.07 (0.7440) | |
| 0.03 (0.9033) | −0.18 (0.3793) | |
| n/a | n/a | |
| n/a | n/a | |
| 0.36 (0.0803) | 0.17 (0.3971) |
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Riggers, D.S.; Xenoulis, P.G.; Karra, D.A.; Enderle, L.L.; Köller, G.; Böttcher, D.; Steiner, J.M.; Heilmann, R.M. Fecal Calprotectin Concentrations in Cats with Chronic Enteropathies. Vet. Sci. 2023, 10, 419. https://doi.org/10.3390/vetsci10070419
Riggers DS, Xenoulis PG, Karra DA, Enderle LL, Köller G, Böttcher D, Steiner JM, Heilmann RM. Fecal Calprotectin Concentrations in Cats with Chronic Enteropathies. Veterinary Sciences. 2023; 10(7):419. https://doi.org/10.3390/vetsci10070419
Chicago/Turabian StyleRiggers, Denise S., Panagiotis G. Xenoulis, Dimitra A. Karra, Lena L. Enderle, Gabor Köller, Denny Böttcher, Joerg M. Steiner, and Romy M. Heilmann. 2023. "Fecal Calprotectin Concentrations in Cats with Chronic Enteropathies" Veterinary Sciences 10, no. 7: 419. https://doi.org/10.3390/vetsci10070419