The Role of Fecal Calprotectin in The Diagnosis and Severity of Ulcerative Colitis

Abstract

Background: The neutrophil-derived protein fecal calprotectin has emerged over the last decade as a novel non-invasive biomarker for the diagnosis and follow-up of intestinal inflammation. Objectives The objective of this study was to assess the diagnostic power and role of severity of fecal calprotectin in patients with ulcerative colitis.

Methods: A case-control study was performed in Al-Najaf City in Iraq at Al-Sadr Medical City, from August 2025 to March 2026. A total of 150 subjects were recruited, comprising 63 patients with clinicopathologically proved ulcerative colitis (UC) and 87 apparently healthy controls. The severity of disease was characterized according to the Mayo scoring system into mild, moderate and severe. All subjects were asked to provide fresh stool samples, and fecal calprotectin concentrations were assessed via a commercially available ELISA. Results: Fecal calprotectin concentrations in patients with ulcerative colitis were significantly greater than those of healthy controls (412.68 ± 136.45 μg/g vs.38.74 ± 14.62 μg/g; p <0.002). Similarly, fecal calprotectin concentration showed stepwise elevation according to disease severity: 218.54 ± 64.27μg/g, 431.86 ± 95.48μg/g and 732.45 ± 128.91μg/g in patients with mild, moderate and severe disease respectively (F =58·73, p <0·001). In the diagnosis of ulcerative colitis, fecal calprotectin showed a sensitivity of 90.5% and specificity of 87.4% at a cut-off value of 85.5 μg/g. Conclusions: Fecal calprotectin stands as a non-invasive biomarker with high sensibility and specificity in the diagnosis of ulcerative colitis, also correlating highly with severity of illness. The sequential accumulation of high fecal calprotectin concentrations with severe disease activity is a further indication of its useful e ness as an indicator of inflammatory burden, which is directly related to treatment choices.

Keywords:

Fecal Calprotectin, Inflammatory Bowel Disease, Ulcerative Colitis

References

Al-Fahham, A.A. (2018) Development of New LSD Formula when Unequal Observations Numbers of Observations Are. Open Journal of Statistics, , 8, 258-263.https://doi.org/10.4236/ojs.2018.82016.

Annisa, E. F. (2025). Fecal calprotectin: A comprehensive systematic review of its diagnostic and monitoring efficacy in inflammatory bowel disease. International Journal of Medical and Health Sciences Research. https://internationalmedicaljournal.org/index.php/ijmhsr/article/view/413

D’Haens, G., Ferrante, M., Vermeire, S., Baert, F., Noman, M., Moortgat, L., Van Assche, G., & Rutgeerts, P. (2012). Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflammatory Bowel Diseases, 18(12), 2218–2224. https://doi.org/10.1002/ibd.22917

D'Amico, F., Baumgart, D. C., Danese, S., & Peyrin-Biroulet, L. (2021). Diagnosis and management of inflammatory bowel disease in the era of precision medicine. United European Gastroenterology Journal, 9(7), 754–765. https://doi.org/10.1002/ueg2.12085

Fagerberg, U. L., Lööf, L., Myrdal, U., Hansson, L. O., & Finkel, Y. (2017). Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms. Journal of Pediatric Gastroenterology and Nutrition, 45(4), 414–420. https://doi.org/10.1097/MPG.0b013e31812e3e42

Khan, N., Ahmed, J., Soomro, I., & Qureshi, M. I. (2022). Fecal calprotectin as a predictor of relapse in ulcerative colitis: A prospective cohort study. Journal of Clinical and Translational Gastroenterology, 13(2), e00456. https://doi.org/10.14309/jctg.0000000000000456

Kostas, A., Siakavellas, S. I., Kosmidis, C., Takou, A., Nikou, J., Maropoulos, G., Vlachogiannakos, J., Papatheodoridis, G. V., Papaconstantinou, I., & Bamias, G. (2017). Fecal calprotectin measurement is a marker of short-term clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease. World journal of gastroenterology, 23(41), 7387–7396. https://doi.org/10.3748/wjg.v23.i41.7387

Li, Y., Chen, Y., & Shi, W. (2021). Clinical value of fecal calprotectin in predicting mucosal healing in patients with ulcerative colitis. Frontiers in Medicine, 8, 679264. https://doi.org/10.3389/fmed.2021.679264

Loftus, E. V., Jr. (2024). Fecal calprotectin assay performs well as biomarker for measurement of ulcerative colitis disease activity. Mayo Clinic Proceedings. https://www.mayoclinic.org/medical-professionals/digestive-diseases/news/fecal-calprotectin-assay-performs-well-as-biomarker-for-measurement-of-ulcerative-colitis-disease-activity/mac-20571579

Ma, C., Feagan, B. G., Kaplan, G. G., Khanna, R., Orza, J., Steinhart, A. H., Van Assche, G., & Torres, J. (2021). Clinical practice guidelines for the management of ulcerative colitis. Inflammatory Bowel Diseases, 27(9), 1486–1504. https://doi.org/10.1093/ibd/izab063

Maaser, C., Sturm, A., Vavricka, S. R., Kucharzik, T., Fiorino, G., Annese, V., Calabrese, E., Baumgart, D. C., Bettenworth, D., Borralho Nunes, P., Burisch, J., Castiglione, F., Eliakim, R., Ellul, P., González-Lama, Y., Gordon, H., Halligan, S., Katsanos, K., Kopylov, U., ... European Crohn’s and Colitis Organisation. (2019). ECCO-ESGAR guideline for diagnostic assessment in inflammatory bowel disease. Journal of Crohn's and Colitis, 13(2), 144–164. https://doi.org/10.1093/ecco-jcc/jjy113

Mao, R., Xiao, Y. L., Gao, X., Chen, B. L., He, Y., Yang, L., Hu, P. J., & Chen, M. H. (2012). Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflammatory bowel diseases, 18(10), 1894–1899. https://doi.org/10.1002/ibd.22861

Menees, S. B., Powell, C., Kurlander, J., Goel, A., & Chey, W. D. (2015). A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. American Journal of Gastroenterology, 110(3), 444–454. https://doi.org/10.1038/ajg.2015.6

Moein, S., Vafaee, Z., & Hosseini, S. M. (2017). Diagnostic accuracy of fecal calprotectin in assessing the severity of inflammatory bowel disease: From laboratory to clinic. Gastroenterology and Hepatology from Bed to Bench, 10(3), 155–162. https://doi.org/10.22037/ghfbb.v10i3.1483

Mosli, M. H., Zou, G., Garg, S. K., Feagan, S. G., MacDonald, J. K., Chande, N., Sandborn, W. J., Feagan, B. G., & Jairath, V. (2015). C-reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: A systematic review and meta-analysis. American Journal of Gastroenterology, 110(6), 802–819. https://doi.org/10.1038/ajg.2015.120

Ng, S. C., Shi, H. Y., Hamidi, N., Underwood, F. E., Tang, W., Benchimol, E. I., Panaccione, R., Ghosh, S., Wu, J. C., Chan, F. K., Sung, J. J., Kaplan, G. G., & Kaplan, G. G. (2018). Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies. The Lancet, 390(10114), 2769–2778. https://doi.org/10.1016/S0140-6736(17)32448-0

Park, J. H., Cheon, J. H., Kim, W. H., Park, D. I., Kim, E. R., Song, J. T., Moon, C. M., Lee, S. H., Kim, H. Y., & Rhee, P. L. (2017). Fecal calprotectin reflects disease activity and predicts recurrence in patients with ulcerative colitis. Journal of Gastroenterology and Hepatology, 32(4), 831–836. https://doi.org/10.1111/jgh.13619

Roseth, A. G., Fagerhol, M. K., Aadland, E., & Schjønsby, H. (1997). Assessment of the neutrophil dominating protein calprotectin in feces. Scandinavian Journal of Gastroenterology, 32(8), 821–828. https://doi.org/10.3109/00365529709011201

Turner, D., Ricciuto, A., Lewis, A., D'Amico, F., Dhaliwal, J., Griffiths, A. M., Bettenworth, D., Sandborn, W. J., Sands, B. E., Reinisch, W., Schölmerich, J., Bemelman, W., Danese, S., Mary, J. Y., Rubin, D., Colombel, J. F., Peyrin-Biroulet, L., Dotan, I., Abreu, M. T., Dignass, A., … International Organization for the Study of IBD (2021). STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology, 160(5), 1570–1583. https://doi.org/10.1053/j.gastro.2020.12.031

Turvill, J., O'Connell, S., Brooks, A., & Bigwood, T. (2016). Evaluation of the clinical and cost-effectiveness of faecal calprotectin in the differential diagnosis of inflammatory bowel disease. Frontline Gastroenterology, 7(4), 279–287. https://doi.org/10.1136/flgastro-2015-100629

Ungaro, R., Mehandru, S., Allen, P. B., Peyrin-Biroulet, L., & Colombel, J. F. (2017). Ulcerative colitis. The Lancet, 389(10080), 1756–1770. https://doi.org/10.1016/S0140-6736(16)32126-2

Waugh, N., Cummins, E., Royle, P., Kandala, N. B., Shyangdan, D., Arasaradnam, R., ... & Lal, S. (2013). Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: Systematic review and economic evaluation. Health Technology Assessment, 17(55), 1–211. https://doi.org/10.3310/hta17550

Ye, X., Wang, Y., Wang, H. H. X., Feng, R., Ye, Z., Han, J., ... & Zhang, S. (2021). Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis. Therapeutic Advances in Gastroenterology, 14, 1756284821994741. https://doi.org/10.1177/1756284821994741