Кальпротектин як біомаркер запалення
DOI:
https://doi.org/10.5281/zenodo.17922702Ключові слова:
Calprotectin, S100A8/A9, inflammation, biomarker, neutrophilsАнотація
Despite the fact that Calprotectin (S100A8/A9) has long been recognized as a sensitive marker for inflammatory bowel diseases, current data broaden the understanding of its use as a sensitive indicator in other inflammatory conditions, including systemic ones. The article analyzes data related to the modern perspective on the use of Calprotectin as an effective marker of inflammation. Fecal Calprotectin is considered an important marker of inflammatory bowel diseases and it is currently used in the differential diagnosis of inflammatory and functional bowel disorders. Serum Calprotectin is regarded as a promising laboratory marker with significant clinical relevance in conditions such as rheumatoid arthritis, hypertension in pregnant women, mild and severe preeclampsia, ileitis, inflammatory kidney diseases, allergic airway inflammations, sepsis, and others. Recent studies have demonstrated that the sensitivity and specificity of serum Calprotectin are comparable to those of well-known acute-phase indicators such as Calprotectin and C-reactive protein, and in certain cases, such as neonatal sepsis, it may even be more promising. Calprotectin has emerged as a highly sensitive biomarker of inflammation across a wide spectrum of pathological conditions. Fecal Calprotectin, in particular, is widely recognized as a validated, non-invasive biomarker for the detection and monitoring of intestinal inflammation. Advances in understanding the activation pathways of various cell types under physiological and pathological conditions have shed light on the involvement of Calprotectin in inflammatory response mechanisms. This has led to increased interest in quantifying S100A8/A9 levels in diverse biological fluids. Recent studies have demonstrated the prognostic value of serum Calprotectin in autoimmune diseases, malignancies, pulmonary disorders, sepsis, and other inflammatory states. The assessment of calprotectin concentrations in urine, synovial fluid, bronchoalveolar lavage, and sputum provides clinically relevant information regarding the severity of inflammation and disease progression. Research findings confirm the importance of Calprotectin as an inflammation biomarker in diseases where neutrophils play a key role in pathogenesis, since the neutrophil protein S100A8/A9 is one of the regulators of their activation.
Посилання
Anceriz N, Vandal K, Tessier PA. S100A9 mediates neutrophil adhesion to fibronectin through activation of beta2 integrins. Biochem Biophys Res Commun. 2007 Mar 2;354(1):84-9. doi: 10.1016/j.bbrc.2006.12.203
Argyris PP, Slama ZM, Ross KF, Khammanivong A, Herzberg MC. Calprotectin and the Initiation and Progression of Head and Neck Cancer. J Dent Res. 2018;97(6):674-682. doi: 10.1177/0022034518756330
Bohn MK, Havelka A, Eriksson M, Adeli K. Validation of Serum Calprotectin Relative to Other Biomarkers of Infection in Febrile Infants Presenting to the Emergency Department. Antibiotics (Basel). 2024 May 7;13(5):425. doi: 10.3390/antibiotics13050425
Carnazzo V, Redi S, Basile V, Natali P, Gulli F, Equitani F, Marino M, Basile U. Calprotectin: two sides of the same coin. Rheumatology (Oxford). 2024 Jan 4;63(1):26-33. doi: 10.1093/rheumatology/kead405
Colicchia M, Perrella G, Gant P, Rayes J. Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation. Res Pract Thromb Haemost. 2023;7(2):100-116. doi: 10.1016/j.rpth.2023.100116
D'Amico F, Rubin DT, Kotze PG, Magro F, Siegmund B, Kobayashi T, et al. International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases. United European Gastroenterol J. 2021; 9(4):451-460. doi: 10.1002/ueg2.12069. https://onlinelibrary.wiley.com/doi/10.1002/ueg2.12069
Dorosz SA, Ginolhac A, Kähne T, Naumann M, Sauter T, Salsmann A, Bueb JL. Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells. Mediators Inflamm. 2015;2015:737310. doi: 10.1155/2015/737310
Hantouly AT, Salameh M, Toubasi AA, Salman LA, Alzobi O, Ahmed AF, Hameed S, Zikria B, Ahmed G. Synovial fluid calprotectin in diagnosing periprosthetic joint infection: A meta-analysis. Int Orthop. 2022 May;46(5):971-981. doi: 10.1007/s00264-022-05357-6
Hu L, Liu Y, Kong X, Wu R, Peng Q, Zhang Y, et al. Fusobacterium nucleatum Facilitates M2 Macrophage Polarization and Colorectal Carcinoma Progression by Activating TLR4/NF-κB/S100A9 Cascade. Front Immunol. 2021 May 21;12:658681. doi: 10.3389/fimmu.2021.658681
Inciarte-Mundo J, Frade-Sosa B, Sanmartí R. From bench to bedside: Calprotectin (S100A8/S100A9) as a biomarker in rheumatoid arthritis. Front Immunol. 2022 Nov 3;13:1001025. doi: 10.3389/fimmu.2022.1001025
Inoue H, Shirakawa J, Togashi Y, Tajima K, Okuyama T, Kyohara M, et al. Signaling between pancreatic β cells and macrophages via S100 calcium-binding protein A8 exacerbates β-cell apoptosis and islet inflammation. J Biol Chem. 2018 Apr 20;293(16):5934-5946. doi: 10.1074/jbc.M117.809228
Jonsson MK, Sundlisæter NP, Nordal HH, Hammer HB, Aga AB, Olsen IC, et al. Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis. Ann Rheum Dis. 2017 Dec;76(12):2031-2037. doi: 10.1136/annrheumdis-2017-211695
Jukic A, Bakiri L, Wagner EF, Tilg H, Adolph TE. Calprotectin: from biomarker to biological function. Gut. 2021;70(10):1978–1988. doi: 10.1136/gutjnl-2021-324855
Kapel N, Ouni H, Benahmed NA, Barbot-Trystram L. Fecal Calprotectin for the Diagnosis and Management of Inflammatory Bowel Diseases. Clin Transl Gastroenterol. 2023;14(9):e00617. doi: 10.14309/ctg.0000000000000617
Kostas A, Siakavellas SI, Kosmidis C, Takou A, Nikou J, Maropoulos G, et al. Fecal calprotectin measurement is a marker of short-term clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease. World J Gastroenterol. 2017;23(41):7387–7396. doi: 10.3748/wjg.v23.i41.7387
Kostrzewska P, Całkosiński A, Majewski M, Malinowski K. Fecal calprotectin as a diagnostic marker of inflammatory bowel disease. Pol Merkur Lekarski. 2022;50(295):58-61
Kotsiou OS, Papagiannis D, Papadopoulou R, Gourgoulianis KI. Calprotectin in Lung Diseases. Int J Mol Sci. 2021 Feb 8;22(4):1706. doi: 10.3390/ijms22041706
Kumar A, Steinkasserer A, Berchtold S. Interleukin-10 influences the expression of MRP8 and MRP14 in human dendritic cells. Int Arch Allergy Immunol. 2003;132(1):40-47. doi: 10.1159/000073263
Lazzarotto ES, Vasco JFM, Führ F, Riedi CA, Filho NAR. Systematic review on fecal calprotectin in cystic fibrosis. J Pediatr (Rio J). 2023 Jan-Feb;99(1):4-10. doi: 10.1016/j.jped.2022.01.006
Liu C, Xing G, Wu C, Zhu J, Wei M, Liu D, et al. Inhibition of Expression of the S100A8 Gene Encoding the S100 Calcium-Binding Protein A8 Promotes Apoptosis by Suppressing the Phosphorylation of Protein Kinase B (Akt) in Endometrial Carcinoma and HEC-1A Cells. Med Sci Monit. 2018 Mar 29;24:1836-1846. doi: 10.12659/msm.908895
Lopez CA, Beavers WN, Weiss A, Knippel RJ, Zackular JP, Chazin W, Skaar EP. The Immune Protein Calprotectin Impacts Clostridioides difficile Metabolism through Zinc Limitation. mBio. 2019 Nov 19;10(6):e02289-19. doi: 10.1128/mBio.02289-19
Mori A, Mitsuyama K, Sakemi R, Yoshioka S, Fukunaga S, Kuwaki K, et al. Evaluation of Serum Calprotectin Levels in Patients with Inflammatory Bowel Disease. Kurume Med J. 2021 Dec 15;66(4):209-215. doi: 10.2739/kurumemedj.MS664009
Nakashige TG, Zhang Bo, Krebs C, Nolan EM. Human calprotectin is an iron-sequestering host-defense protein. Nat Chem Biol. 2015;11(10):765-771. doi: 10.1038/nchembio.1891
Noor NM, Lee JC, Bond S, Dowling F, Brezina B, Patel KV, et al. PROFILE Study Group. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May; 9(5):415-427. doi: 10.1016/S2468-1253(24)00034-7. Epub 2024 Feb 22. Erratum in: Lancet Gastroenterol Hepatol. 2025 Aug;10(8):e10. doi: 10.1016/S2468-1253(25)00203-1
Ometto F, Friso L, Astorri D, Botsio C, Raffeiner B, Punzi L, Doria A. Calprotectin in rheumatic diseases. Exp Biol Med (Maywood). 2016 Nov 28;242(8):859–873. doi: 10.1177/1535370216681551
Palmer LD, Maloney KN, Boyd KL, Goleniewska AK, Toki S, Maxwell CN, et al. The Innate Immune Protein S100A9 Protects from T-Helper Cell Type 2-mediated Allergic Airway Inflammation. Am J Respir Cell Mol Biol. 2019 Oct;61(4):459-468. doi: 10.1165/rcmb.2018-0217OC
Reshadmanesh T, Behnoush AH, Farajollahi M, Khalaji A, Ghondaghsaz E, Ahangar H. Circulating Levels of Calprotectin as a Biomarker in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis. Clin Cardiol. 2024 Jul;47(7):e24315. doi: 10.1002/clc.24315
Rezniczek GA, Förster C, Hilal Z, Westhoff T, Tempfer CB. Calprotectin in pregnancy and pregnancy-associated diseases: a systematic review and prospective cohort study. Arch Gynecol Obstet. 2019 Jun;299(6):1567-1577. doi: 10.1007/s00404-019-05134-8
Saviano A, Migneco A, Brigida M, Petruzziello C, Zanza C, Savioli G, et al. Serum Calprotectin in the Evaluation of Gastrointestinal Diseases: An Ace up Your Sleeve? Medicina (Kaunas). 2024;60(5):762. doi: 10.3390/medicina60050762
Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM. Biomarkers in acute kidney injury - pathophysiological basis and clinical performance. Acta Physiol (Oxf). 2017 Mar;219(3):554-572. doi: 10.1111/apha.12764
Steinbakk M, Naess-Andresen CF, Lingaas E, Dale I, Brandtzaeg P, Fagerhol MK. Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet. 1990;336(8718):763-775. doi: 10.1016/0140-6736(90)93237-j2
Stríz I, Trebichavský I. Calprotectin - A pleiotropic molecule in acute and chronic inflammation. Physiol. Res. 2004;53:245–253. doi: 10.33549/physiolres.930448
Vincent Z, Hornby S, Ball S, Sanders G, Ayling RM. Faecal calprotectin as a marker for oesophago-gastric cancer. Ann Clin Biochem. 2015;52(Pt 6):660-664. doi: 10.1177/0004563215578191
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(13):4260–8. doi: 10.1182/blood-2004-02-0446
Wirtz TH, Buendgens L, Weiskirchen R, Loosen SH, Haehnsen N, Puengel T, et al. Association of Serum Calprotectin Concentrations with Mortality in Critically Ill and Septic Patients. Diagnostics. 2020;10:990. doi: 10.3390/diagnostics10110990
Wu M, Xu L, Wang Y, Zhou N, Zhen F, Zhang Y, et al. S100A8/A9 induces microglia activation and promotes the apoptosis of oligodendrocyte precursor cells by activating the NF-κB signaling pathway. Brain Res Bull. 2018 Oct;143:234-245. doi: 10.1016/j.brainresbull.2018.09.014
Yang J, Wu Z, Long Q, Huang J, Hong T, Liu W, Lin J. Insights into Immunothrombosis: The Interplay among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13. Front. Immunol. 2020;11:610696. doi: 10.3389/fimmu.2020.610696
##submission.downloads##
Опубліковано
Як цитувати
Номер
Розділ
Ліцензія
Авторське право (c) 2025 Анали Мечниковського Інституту

Ця робота ліцензується відповідно до Creative Commons Attribution 4.0 International License.