The level of interleukin-6, serum calprotectin, and hypersensitive C-reactive protein in Crohn's disease-related mucosal damage
Serum calprotectin, hypersensitive CRP, and interleukin-6 in gut mucosal damage
Abstract
[Objective] To evaluate calprotectin, hypersensitive C-reactive protein, and interleukin-6 for detecting digestive tract mucosal injury in Crohn's disease (CD) patients.
[Methods] 52 patients diagnosed with CD were selected. Fecal samples from the patients were collected to detect calprotectin (ELISA), and serum samples were collected to detect hs-CRP (Immunoturbidimetry) and IL-6 (Chemiluminescence). All patients with CD underwent colonoscopy or capsule endoscopy. According to the modified endoscopic severity index of CD (SES-CD). Comparisons were made between the two groups' variations in calprotectin, hs-CRP, and IL-6 levels, and ROC curves were drawn to analyze the diagnostic efficacy (AUC) of each index and combined detection for mucosal injury.
[Results] In the Mucosal injury group, the calprotectin, hs-CRP levels were significantly greater than those in the mucosal healing group. Calprotectin had the highest AUC (0.93, 95% CI: 0.88–0.98), sensitivity (88.5%), and specificity (89.2%) when the critical value was greater than 250μg/g, according to ROC analysis. The AUC of the three indicators' combined detection (logistic regression model) rose to 0.96, which was noticeably superior than that of a single indicator (P<0.05).
[Conclusion] Interleukin-6, serum calprotectin, and hypersensitive C-reactive protein levels are significantly correlated with the degree of mucosal injury in patients with CD. Among them, calprotectin has the best diagnostic value. The combined detection of these three factors can significantly improve the recognition of mucosal injury in the active stage of CD.
References
2.Cioffi I, Scialò F, Di Vincenzo O, Gelzo M, Marra M, Testa A, Castiglione F, Vitale M, Pasanisi F, Santarpia L. Serum Interleukin 6, Controlling Nutritional Status (CONUT) Score and Phase Angle in Patients with Crohn's Disease. Nutrients. 2023 Apr 18;15(8):1953. doi: 10.3390/nu15081953. PMID: 37111172; PMCID: PMC10146872.
3.Xiao L, Yang JP, Wang W. [Application of TIGIT combined with interleukin-6 detection in the evaluation of Crohn's disease status]. Zhonghua Yu Fang Yi Xue Za Zhi. 2023 Aug 6;57(8):1253-1258. Chinese. doi: 10.3760/cma.j.cn112150-20230319-00202. PMID: 37574320.
4.Garbers C, Lokau J. Cytokines of the interleukin-6 family as emerging targets in inflammatory bowel disease. Expert Opin Ther Targets. 2024 Jan-Feb;28(1-2):57-65. doi: 10.1080/14728222.2024.2306341. Epub 2024 Jan 23. PMID: 38217849.
5.Shahini A, Shahini A. Role of interleukin-6-mediated inflammation in the pathogenesis of inflammatory bowel disease: focus on the available therapeutic approaches and gut microbiome. J Cell Commun Signal. 2023 Mar;17(1):55-74. doi: 10.1007/s12079-022-00695-x. Epub 2022 Sep 16. PMID: 36112307; PMCID: PMC10030733.
6.Friedberg S, Choi D, Hunold T, Choi NK, Garcia NM, Picker EA, Cohen NA, Cohen RD, Dalal SR, Pekow J, Sakuraba A, Krugliak Cleveland N, Rubin DT. Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1913-1923.e2. doi: 10.1016/j.cgh.2023.03.001. Epub 2023 Mar 8. PMID: 36898598; PMCID: PMC11016252.
7.Yanai H, Levine A, Hirsch A, Boneh RS, Kopylov U, Eran HB, Cohen NA, Ron Y, Goren I, Leibovitzh H, Wardi J, Zittan E, Ziv-Baran T, Abramas L, Fliss-Isakov N, Raykhel B, Gik TP, Dotan I, Maharshak N. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5. Epub 2021 Nov 2. PMID: 34739863.
8.Noor NM, Lee JC, Bond S, Dowling F, Brezina B, Patel KV, Ahmad T, Banim PJ, Berrill JW, Cooney R, De La Revilla Negro J, de Silva S, Din S, Durai D, Gordon JN, Irving PM, Johnson M, Kent AJ, Kok KB, Moran GW, Mowat C, Patel P, Probert CS, Raine T, Saich R, Seward A, Sharpstone D, Smith MA, Subramanian S, Upponi SS, Wiles A, Williams HRT, van den Brink GR, Vermeire S, Jairath V, D'Haens GR, McKinney EF, Lyons PA, Lindsay JO, Kennedy NA, Smith KGC, Parkes M; 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. PMID: 38402895; PMCID: PMC11001594.
9.Bao C, Wu L, Wang D, Chen L, Jin X, Shi Y, Li G, Zhang J, Zeng X, Chen J, Liu H, Wu H. Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial. EClinicalMedicine. 2022 Feb 12;45:101300. doi: 10.1016/j.eclinm.2022.101300. PMID: 35198926; PMCID: PMC8850329.
10.Ananthakrishnan AN, Adler J, Chachu KA, Nguyen NH, Siddique SM, Weiss JM, Sultan S, Velayos FS, Cohen BL, Singh S; AGA Clinical Guidelines Committee. Electronic address: clinicalpractice@gastro.org. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease. Gastroenterology. 2023 Dec;165(6):1367-1399. doi: 10.1053/j.gastro.2023.09.029. PMID: 37981354.
11.Wu L, Zheng Y, Liu J, Luo R, Wu D, Xu P, Wu D, Li X. Comprehensive evaluation of the efficacy and safety of LPV/r drugs in the treatment of SARS and MERS to provide potential treatment options for COVID-19. Aging (Albany NY). 2021 Apr 20;13(8):10833-10852. doi: 10.18632/aging.202860. Epub 2021 Apr 20. PMID: 33879634; PMCID: PMC8109137.
12.Ferrante M, Irving PM, Abreu MT, Axler J, Gao X, Cao Q, Fujii T, Rausch A, Torres J, Neimark E, Song A, Wallace K, Kligys K, Berg S, Liao X, Zhou Q, Kalabic J, Feagan B, Panaccione R. Maintenance Risankizumab Sustains Induction Response in Patients with Crohn's Disease in a Randomized Phase 3 Trial. J Crohns Colitis. 2024 Mar 1;18(3):416-423. doi: 10.1093/ecco-jcc/jjad168. PMID: 37797293; PMCID: PMC10906949.
13.Wu L, Zhong Y, Wu D, Xu P, Ruan X, Yan J, Liu J, Li X. Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis. Biomedicines. 2022 Sep 10;10(9):2248. doi: 10.3390/biomedicines10092248. PMID: 36140350; PMCID: PMC9496572.
14.Akutko K, Iwańczak B. Evaluation of Fecal Calprotectin, Serum C-Reactive Protein, Erythrocyte Sedimentation Rate, Seromucoid and Procalcitonin in the Diagnostics and Monitoring of Crohn's Disease in Children. J Clin Med. 2022 Oct 15;11(20):6086. doi: 10.3390/jcm11206086. PMID: 36294408; PMCID: PMC9604851.
15.Yan W, Meihao W, Zihan S, Lingjie H, Haotian C, Qian C, Lianli S. Correlation Between Crohn's Disease Activity and Serum Selenium Concentration. Clin Ther. 2022 May;44(5):736-743.e3. doi: 10.1016/j.clinthera.2022.03.005. Epub 2022 Apr 1. PMID: 35369995.
16.Wu L, Liu Q, Ruan X, Luan X, Zhong Y, Liu J, Yan J, Li X. Multiple Omics Analysis of the Role of RBM10 Gene Instability in Immune Regulation and Drug Sensitivity in Patients with Lung Adenocarcinoma (LUAD). Biomedicines. 2023 Jun 29;11(7):1861. doi: 10.3390/biomedicines11071861. PMID: 37509501; PMCID: PMC10377220.
17.Guyard C, de Ponthaud C, Frontali A, Monsinjon M, Giacca M, Panis Y. C-reactive protein monitoring after ileocecal resection and stoma closure reduces length of hospital stay: a prospective case-matched study in 410 patients with Crohn's disease. Tech Coloproctol. 2022 Jun;26(6):443-451. doi: 10.1007/s10151-022-02590-4. Epub 2022 Mar 3. PMID: 35239097.
18.Wu L, Zheng Y, Ruan X, Wu D, Xu P, Liu J, Wu D, Li X. Long-chain noncoding ribonucleic acids affect the survival and prognosis of patients with esophageal adenocarcinoma through the autophagy pathway: construction of a prognostic model. Anticancer Drugs. 2022 Jan 1;33(1):e590-e603. doi: 10.1097/CAD.0000000000001189. PMID: 34338240; PMCID: PMC8670349.
19.Takakura WR, Mirocha J, Ovsepyan G, Zaghiyan KN, Syal G, Fleshner P. Magnitude of Preoperative C-Reactive Protein Elevation Is Associated With De Novo Crohn's Disease After Ileal Pouch-Anal Anastomosis in Patients With Severe Colitis. Dis Colon Rectum. 2022 Mar 1;65(3):399-405. doi: 10.1097/DCR.0000000000002148. PMID: 34657077.
20.Zinger A, Choi D, Choi N, Fear E, Fine Z, Cohen RD, Rubin DT. Long-term Effectiveness and Safety of Risankizumab in Patients with Crohn's Disease. Clin Gastroenterol Hepatol. 2024 Oct 24:S1542-3565(24)00968-6. doi: 10.1016/j.cgh.2024.09.027. Epub ahead of print. PMID: 39461462.
21.Adedokun OJ, Xu Z, Gasink C, Kowalski K, Sandborn WJ, Feagan B. Population Pharmacokinetics and Exposure-Response Analyses of Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease. Clin Ther. 2022 Oct;44(10):1336-1355. doi: 10.1016/j.clinthera.2022.08.010. Epub 2022 Sep 21. PMID: 36150926.
22.Wu L, Zhong Y, Yu X, Wu D, Xu P, Lv L, Ruan X, Liu Q, Feng Y, Liu J, Li X. Selective poly adenylation predicts the efficacy of immunotherapy in patients with lung adenocarcinoma by multiple omics research. Anticancer Drugs. 2022 Oct 1;33(9):943-959. doi: 10.1097/CAD.0000000000001319. Epub 2022 Aug 9. PMID: 35946526; PMCID: PMC9481295.
23.Brodersen JB, Kjeldsen J, Juel MA, Knudsen T, Rafaelsen SR, Jensen MD. Changes in Endoscopic Activity and Classification of Lesions With Panenteric Capsule Endoscopy in Patients Treated for Crohn's Disease-A Prospective Blinded Comparison With Ileocolonoscopy, Fecal Calprotectin, and C-Reactive Protein. J Crohns Colitis. 2025 Jan 11;19(1):jjae124. doi: 10.1093/ecco-jcc/jjae124. PMID: 39126260.
24.Takada Y, Kiyohara H, Mikami Y, Taguri M, Sakakibara R, Aoki Y, Nanki K, Kawaguchi T, Yoshimatsu Y, Sugimoto S, Sujino T, Takabayashi K, Hosoe N, Ogata H, Kato M, Iwao Y, Nakamoto N, Kanai T. Leucine-rich alpha-2 glycoprotein in combination with C-reactive protein for predicting endoscopic activity in Crohn's disease: a single-centre, cross-sectional study. Ann Med. 2025 Dec;57(1):2453083. doi: 10.1080/07853890.2025.2453083. Epub 2025 Jan 17. PMID: 39823192; PMCID: PMC11748989.
25.Moskow J, Thurston T, Saleh A, Shah A, Abraham BP, Glassner K. Postoperative Ustekinumab Drug Levels and Disease Activity in Patients with Crohn's Disease. Dig Dis Sci. 2024 Aug;69(8):2944-2954. doi: 10.1007/s10620-024-08471-0. Epub 2024 May 24. PMID: 38789673.
26.Pierre N, Vieujean S, Peyrin-Biroulet L, Meuwis MA, Louis E. Defining Biological Remission in Crohn's Disease: Interest, Challenges and Future Directions. J Crohns Colitis. 2023 Nov 8;17(10):1698-1702. doi: 10.1093/ecco-jcc/jjad086. PMID: 37208498.
27.Muresan S, Slevin M. C-reactive Protein: An Inflammatory Biomarker and a Predictor of Neurodegenerative Disease in Patients With Inflammatory Bowel Disease? Cureus. 2024 Apr 25;16(4):e59009. doi: 10.7759/cureus.59009. PMID: 38665135; PMCID: PMC11045161.
28.Glapa-Nowak A, Szczepanik M, Banaszkiewicz A, Kwiecień J, Szaflarska-Popławska A, Grzybowska-Chlebowczyk U, Osiecki M, Kierkuś J, Dziekiewicz M, Walkowiak J. C-Reactive Protein/Albumin Ratio at Diagnosis of Pediatric Inflammatory Bowel Disease: A Retrospective Multi-Center Study. Med Sci Monit. 2022 Sep 14;28:e937842. doi: 10.12659/MSM.937842. PMID: 36101481; PMCID: PMC9484282.
29.Santos RCFD, Catapani WR, Takahashi AAR, Waisberg J. C-reactive protein levels and prevalence of leukopenia in patients with inflammatory bowel disease treated with azathioprine and/or mesalazine: a real-life study. Einstein (Sao Paulo). 2022 May 6;20:eAO6500. doi: 10.31744/einstein_journal/2022AO6500. PMID: 35584442; PMCID: PMC9060644.
30.Koifman E, Krasnopolsky M, Ghersin I, Waterman M. Persistently Elevated C-Reactive Protein Levels and Low Body Mass Index Are Associated with a Lack of Improvement in Bone Mineral Density in Crohn's Disease. Nutrients. 2024 Aug 23;16(17):2827. doi: 10.3390/nu16172827. PMID: 39275145; PMCID: PMC11396862.
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