The role of serum calprotectin as a novel biomarker in inflammatory bowel diseases: a review study
Gastroenterology and Hepatology from Bed to Bench,
As the incidence of inflammatory bowel diseases (IBD) increases in the newly industrialized countries, the health and financial burden of disease also increase. These changes make the role of IBD biomarkers further crucial. Serum calprotectin, as a novel blood-based biomarker of IBD, has been investigated in several investigations. Yet, there is no consensus regarding its clinical utility. We searched the electronic database, including PubMed, EMBASE, Scopus, and Web of Science up to the end of 2018 to find how serum calprotectin associates with the disease characteristics in IBD. The search terms included: inflammatory bowel diseases, IBD, Crohn Diseases (CD), Ulcerative Colitis (UC), calprotectin, serum, and blood. Based on our review, a biomarker role has been suggested for serum calprotectin in IBD, as significant associations were found between serum calprotectin and disease burden, prognosis, and relapse. A complementary role to fecal calprotectin has also been suggested for serum calprotectin. On the other hand, considering a significant correlation between serum calprotectin and serum CRP, but not fecal calprotectin, serum calprotectin could be more representative of systemic inflammation than an intestinal inflammation. Consequently, further researches are needed to unwrap the potential of serum calprotectin as a blood-based biomarker in IBD.
Keywords: Inflammatory bowel diseases, Serum calprotectin, Biomarker.
(Please cite as: Azramezani Kopi T, Shahrokh SH, Mirzaei A, Asadzadeh Aghdaei H, Amini Kadijani A. The role of serum calprotectin as a novel biomarker in inflammatory bowel diseases: a review study. Gastroenterol Hepatol Bed Bench 2019;12(3):183-89).
- Inflammatory bowel diseases
- serum calprotectin
How to Cite
Wallace KL, Zheng LB, Kanazawa Y, Shih DQ. Immunopathology of inflammatory bowel disease. World J gastroenterol 2014;20:6.
Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immuno 2008;8:458.
Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017;390:2769-78.
Norouzinia M, Chaleshi V, Alinaghi S, Beheshti Shirazi SS, Keramatinia A, Nourian M. Evaluation of IL-12A, IL-12B, IL-23A and IL-27 mRNA expression level genes in peripheral mononuclear cells of inflammatory bowel disease patients in an Iranian population. Gastroenterol Hepatol Bed Bench 2018;11:S45-S52.
Norouzinia M, Chaleshi V, Alizadeh AHM, Zali MR. Biomarkers in inflammatory bowel diseases: insight into diagnosis, prognosis and treatment. Gastroenterol Hepatol Bed Bench 2017;10:155-167.
Falvey JD, Hoskin T, Meijer B, Ashcroft A, Walmsley R, Day AS, et al. Disease activity assessment in IBD: clinical indices and biomarkers fail to predict endoscopic remission. Inflammat Bowel Dis 2015;21:824-31.
Iskandar HN, Ciorba MA. Biomarkers in inflammatory bowel disease: current practices and recent advances. Trans Res 2012;159:313-25.
Amini AK, Asadzadeh HA, Sorrentino D, Mirzaei A, Shahrokh S, Balaii H, et al. Transmembrane TNF-α Density, but not Soluble TNF-α Level, is Associated with Primary Response to Infliximab in Inflammatory Bowel Disease. Clin Trans Gastroenterol 2017;8:e117-e.
Aghdaei HA, Kadijani AA, Sorrentino D, Mirzaei A, Shahrokh S, Balaii H, et al. An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients. United Europ Gastroenterol J 2018:2050640618774637.
Pardi D, Sandborn W. Predicting relapse in patients with inflammatory bowel disease: what is the role of biomarkers? Gut 2005;54:321-2.
Kadijani AA, Javadinia F, Gholamrezaei Z, Mirzaei A, Balaii H, Ghavami SB, et al. Apoptosis markers of circulating leukocytes are associated with the clinical course of inflammatory bowel disease. Gastroenterol Hepatol Bed Bench 2018;11:S53-8.
Kadijani AA, Shahrokh S, Haghazali M, Aghdaei HA, Mirzaei A. Inducible nitric oxide synthase as a potential blood-based biomarker in inflammatory bowel diseases. Gastroenterol Hepatol Bed Bench 2018;11:S124-8.
Peyrin-Biroulet L, Standaert-Vitse A, Branche J, Chamaillard M. IBD serological panels: facts and perspectives. Inflammat Bowel Dis 2007;13:1561-6.
Reumaux D, Sendid B, Poulain D, Duthilleul P, Dewit O, Colombel JF. Serological markers in inflammatory bowel diseases. Best practice & research Clinical gastroenterology. 2003;17:19-35.
Van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 2010;341:c3369.
Bjarnason I. The use of fecal calprotectin in inflammatory bowel disease. Gastroenterol Hepatol 2017;13:53.
Fukunaga S, Kuwaki K, Mitsuyama K, Takedatsu H, Yoshioka S, Yamasaki H, et al. Detection of calprotectin in inflammatory bowel disease: Fecal and serum levels and immunohistochemical localization. Inter J Molecul Med 2018;41:107-18.
Meuwis MA, Vernier-Massouille G, Grimaud J, Bouhnik Y, Laharie D, Piver E, et al. Serum calprotectin as a biomarker for Crohn's disease. J Crohn's Colitis 2013;7:e678-83.
Nacken W, Roth J, Sorg C, Kerkhoff C. S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. Microsco Res Techniq 2003;60:569-80.
Ehrchen JM, Sunderkötter C, Foell D, Vogl T, Roth J. The endogenous Toll–like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J leukoc Biol 2009;86:557-66.
Sohnle PG, Hunter MJ, Hahn B, Chazin WJ. Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor—related proteins 8 and 14). J Infect Dis 2000;182:1272-5.
Clark MA, Plank LD, Connolly AB, Streat SJ, Hill AA, Gupta R, et al. Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis-a randomized, clinical trial. Critical Care Med 1998;26:1650-9.
Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, et al. MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood 2004;104:4260-8.
Kerkhoff C, Nacken W, Benedyk M, Dagher MC, Sopalla C, Doussiere J. The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67 phox and Rac-2. FASEB J 2005;19:467-9.
Dhas DBB, Bhat BV, Gane DB. Role of calprotectin in infection and inflammation. Current Pediatr Res 2012;16.
Björk P, Björk A, Vogl T, Stenström M, Liberg D, Olsson A, et al. Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides. PLoS Biol 2009;7:e1000097.
Leclerc E, Fritz G, Vetter SW, Heizmann CW. Binding of S100 proteins to RAGE: an update. Biochim Biophys Acta 2009;1793:993-1007.
Robinson MJ, Tessier P, Poulsom R, Hogg N. The S100 family heterodimer, MRP-8/14, binds with high affinity to heparin and heparan sulfate glycosaminoglycans on endothelial cells. J Biol Chem 2002;277:3658-65.
Viemann D, Strey A, Janning A, Jurk K, Klimmek K, Vogl T, et al. Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells. Blood 2005;105:2955-62.
Mumolo MG, Bertani L, Ceccarelli L, Laino G, Di Fluri G, Albano E, et al. From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 2018;24:3681.
Gisbert J, McNicholl A. Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease. Dig Liver Dis 2009;41:56-66.
Heida A, Park K, van Rheenen PF. Clinical utility of fecal calprotectin monitoring in asymptomatic patients with inflammatory bowel disease: a systematic review and practical guide. Inflammat Bowel Dis 2017;23:894-902.
Schoepfer AM, Beglinger C, Straumann A, Trummler M, Vavricka SR, Bruegger LE, et al. Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol 2010;105:162.
D'haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflammat Bowel Dis 2012;18:2218-24.
Costa F, Mumolo M, Ceccarelli L, Bellini M, Romano M, Sterpi C, et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut 2005;54:364-8.
Walsham NE, Sherwood RA. Fecal calprotectin in inflammatory bowel disease. Clin Exp Gastroenterol 2016;9:21.
Kalla R, Kennedy NA, Ventham NT, Boyapati RK, Adams AT, Nimmo ER, et al. Serum calprotectin: a novel diagnostic and prognostic marker in inflammatory bowel diseases. Am J Gastroenterol 2016;111:1796.
Hare N, Kennedy N, Kingstone K, Arnott I, Shand A, Palmer K, et al. PTH-082 Serum Calprotectin: A Novel Biomarker to Predict Outcome in Acute Severe Ulcerative Colitis? Gut 2013;62:A244-5.
Lügering N, Stoll R, Kucharzik T, Schmid KW, Rohlmann G, Burmeister G, et al. Immunohistochemical distribution and serum levels of the Ca2+-binding proteins MRP8, MRP14 and their heterodimeric form MRP8/14 in Crohn’s disease. Dig 1995;56:406-14.
Leach ST, Yang Z, Messina I, Song C, Geczy CL, Cunningham AM, et al. Serum and mucosal S100 proteins, calprotectin (S100A8/S100A9) and S100A12, are elevated at diagnosis in children with inflammatory bowel disease. Scandinavian J gastroenterol 2007;42:1321-31.
Pepper RJ, Hamour S, Chavele KM, Todd SK, Rasmussen N, Flint S, et al. Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis. Kidney Inter 2013;83:1150-8.
McCann RK, Smith K, Gaya DR. A prospective single centre pilot evaluation of a serum calprotectin assay in unselected GI patients. Clin Biochem 2017;50:533-6.
- Abstract Viewed: 135 times
- PDF Downloaded: 85 times