Evaluation of Serum Annexin A1 Values in Patients with Inflammatory Bowel Diseases

Year 2024, Volume: 16 Issue: 1, 11 - 19, 14.03.2024

İrfan Küçük Yusuf Yazgan İdris Yıldırım Tuğba Akbaş Şimşek Başak Çakır Güney Musa Salmanoğlu Mustafa Kaplan

https://doi.org/10.18521/ktd.1373002

Abstract

Objective: Annexin A1(AnxA1) is an anti-inflammatory mediator. In the current study,we aimed to evaluate whether or not serum Annexin A1 levels of inflammatory boweldiseases (IBDs) patients relate to the clinical and laboratory traits of IBDs.
Methods: This case-control study included 67 ulcerative colitis (UC) patients (47 males and 20 females), 53 Crohn’s disease (CD) patients (37 males and 16 females) and 60 healthy controls (36 males and 24 females). The Mayo Clinical scoring system (MCS) was used for UC and the histological activity index (HAI) was determined by Truelove and Richards method. The Crohn's disease activity index (CDAI) was used for CD patients. Montreal classification was used for the localization of IBDs.
Results: The mean serum AnxA1 concentrations were not statistically significant in UC, CD and the control groups (26.36±17.30 ng/ml vs 22.98±12.74 vs 24.45±12.18 ng/ml respectively, p=0.404). The MCS, HAI of UC patients negatively correlated with the serum AnxA1 values (rho=-0.616, p<0.001 vs rho=-0.778, p<0.001 respectively). UC patients with limited disease had higher values than those with extensive disease (19.5 (IQR:14.5–47.8) ng/ml vs.13.4 (IQR:10.8–18.4) ng/ml respectively, p=0.002). In CD patients, CDAI values negatively correlated to the serum AnxA1 values (rho=-0.770, p<0.001).
Conclusions: Serum AnxA1 values might be an auxiliary biomarker for the disease activity in patients with IBDs.

Keywords

Ulcerative colitis, Crohn's disease, Annexin A1, activity

Ethical Statement

The Local Ethics Committee of Sancaktepe Prof. İ. VARANK Training and Research Hospital (11.01.2023/05) approved the study.

Supporting Institution

None

Thanks

Special thanks to all members of Sultan 2. Abdulhamid Han Training and Research Hospital endoscopy, biochemistry and pathology departments who supported and included in the study. Additionally, special acknowledgment is dedicated to the members of the Farmasina Medical Laboratories who carried out the ELISA studies.

İnflamatuvar Bağırsak Hastalıklarında Serum Annexin A1 Düzeylerinin Değerlendirilmesi

Abstract

Amaç: Annexin A1 (AnxA1) anti-inflamatuar bir moleküldür. Çalışmamızda, inflamatuar barsak hastalıklarında (İBH) serum Annexin A1 düzeylerinin hastalıkların klinik ve laboratuvar özellikleri ile ilişkili olup olmadığı araştırılmıştır.
Gereç ve Yöntem: Bu vaka-kontrol çalışmasına 67 ÜK hastası, 53 Crohn hastalığı (CH) hastası ve 60 sağlıklı kontrol dahil edilmiştir. ÜK klinik aktivitesi için Mayo klinik skorlama sistemi (MKS) kullanıldı, histolojik aktivite indeksi (HAİ) Truelove ve Richards yöntemiyle belirlendi. CH için Crohn hastalığı aktivite indeksi (CHAİ) kullanıldı. İBH lokalizasyonu için Montreal sınıflandırması kullanıldı.
Bulgular: ÜK, CH ve kontrol grupları arasinda ortalama serum AnxA1 konsantrasyonları yönünden fark saptanmadı (26,36±17,30 ng/ml vs 22,98±12,74 vs 24,45±12,18 ng/ml, sırasıyla p=0,404). ÜK’de MKS, HAİ ve serum AnxA1 değerleri arasında negatif korelasyon tespit edildi (rho=-0,616, p<0,001 vs rho=-0,778, sırasıyla p<0,001). Sınırlı hastalığı olan ÜK hastalarında, yaygın hastalığı olanlara göre daha yüksek serum AnxA1 değerleri bulundu (19,5 (IQR:14,5–47,8) ng/ml ve 13,4 (IQR:10,8–18,4) ng/ml, sırasıyla p=0,002). CH’da serum AnxA1 değerleri ile CHAİ arasında negatif korelasyon bulundu (rho=-0,770, p<0,001).
Sonuç: Serum AnxA1 düzeyleri İBH’da hastalık aktivite tespiti için yardımcı bir biyobelirteç olabilir.

Keywords

İnflamatuar bağırsak hastalığı, Annexin A1

References

• 1. Body-Malapel M, Djouina M, Waxin C, Langlois A, Gower-Rousseau C, Zerbib P, et al. The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases. Mucosal Immunol. 2019;12(2):468-78.
• 2. Perretti M, Dalli J. Resolution Pharmacology: Focus on Pro-Resolving Annexin A1 and Lipid Mediators for Therapeutic Innovation in Inflammation. Annu Rev Pharmacol Toxicol. 2023;(63):449-69.
• 3. Serhan CN, Levy BD. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest. 2018;128(7):2657-69.
• 4. Abdolmaleki F, Kovanen PT, Mardani R, Gheibi-Hayat SM, Bo S, Sahebkar A. Resolvins: Emerging Players in Autoimmune and Inflammatory Diseases. Clin Rev Allergy Immunol. 2020;58(1):82-91.
• 5. Nakov R. New markers in ulcerative colitis. Clin Chim Acta. 2019; 497:141-46.
• 6. Leoni G, Alam A, Neumann PA, Lambeth JD, Cheng G, McCoy J, et al. Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair. J Clin Invest. 2013;123(1):443-54.
• 7. Williams SL, Milne IR, Bagley CJ, Gamble JR, Vadas MA, Pitson SM, et al. A proinflammatory role for proteolytically cleaved Annexin A1 in neutrophil transendothelial migration. J Immunol. 2010;(185):3057–63.
• 8. Kelly L, McGrath S, Rodgers L, McCall K, Tulunay Virlan A, Dempsey F, et al. Annexin-A1: The culprit or the solution? Immunology. 2022;166(1):2-16.
• 9. Vong L, Ferraz JG, Dufton N, Panaccione R, Beck PL, Sherman PM, et al. Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis. PLoS One. 2012;7(6):e39244.
• 10. Kourkoulis P, Michalopoulos G, Katifelis H, Giannopoulou I, Lazaris AC, Papaconstantinou I, et al. Leucine-rich alpha-2 glycoprotein 1, high mobility group box 1, matrix metalloproteinase 3 and annexin A1 as biomarkers of ulcerative colitis endoscopic and histological activity. Eur J Gastroenterol Hepatol. 2020;32(9):1106-15.
• 11. Sena A, Grishina I, Thai A, Goulart L, Macal M, Fenton A, et al. Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns Disease. PLoS One. 2013;8(10):e76969.
• 12. Reischl S, Troger J, Jesinghaus M, Kasajima A, Wilhelm DF, Friess H, et al. Annexin A1 Expression Capacity as a Determinant for Disease Severity in Crohn's Disease. Dig Dis. 2020;38(5):398-407.
• 13. de Paula-Silva M, da Rocha GHO, Broering MF, Queiroz ML, Sandri S, Loiola RA, et al. Formyl Peptide Receptors and Annexin A1: Complementary Mechanisms to Infliximab in Murine Experimental Colitis and Crohn's Disease. Front Immunol. 2021 Sep 17;(12):714138.
• 14. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317(26):1625-29.
• 15. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology. 1976;70(3):439-44.
• 16. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol Hepatol 2005; 19: 5A-36A.
• 17. Truelove SC, Richards WCD. Biopsy studies in ulcerative colitis. BMJ. 1956; 1:1315-18.
• 18. Osterman MT, Lichtenstein GR. Ulcerative Colitis. In: Feldman M, Friedman SL. Brandt JL. (Eds). Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Philadelphia: Elselvier Saunders;Volume 2; 2016:2023-61.
• 19. Rhen T, Cidlowski JA. Anti-inflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-23.
• 20. Pineton de Chambrun G, Peyrin-Biroulet L, Lémann M, Colombel JF. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol. 2010;7(1):15-29.
• 21. Coméra C, Brousset P, Moré J, Vergnolle N, Buéno L. Inflammatory neutrophils secrete Annexin A1 during experimentally induced colitis in rats. Dig Dis Sci. 1999;44(7):1448-57.
• 22. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. “Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extraintestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders,” Journal of Crohn's & Colitis, 2017;11(6):649-70.
• 23. Steinsbø Ø, Carlsen A, Aasprong OG, Aabakken L, Tvedt-Gundersen E, Bjørkhaug S, et al. Histologic healing and factors associated with complete remission following conventional treatment in ulcerative colitis. Therap Adv Gastroenterol. 2022;15:17562848221140659.
• 24. Chen F, Hu Y, Fan YH, Lv B. Clinical Value of Fecal Calprotectin in Predicting Mucosal Healing in Patients with Ulcerative Colitis. Front Med (Lausanne). 2021;8: 679264.