İrfan KÜÇÜK, Ersin TURAL, Yusuf YAZGAN, Başak ÇAKIR GÜNEY, İdris YILDIRIM, Tuğba AKBAŞ ŞİMŞEK, Musa SALMANOĞLU

Serum-soluble receptor for advanced glycation end-products values might have diagnostic and prognostic significances in ulcerative colitis

Giriş: Serum ileri glikasyon son ürünleri reseptörlerinin (sRAGE) anti-inflamatuar özellik gösterdikleri bilinmektedir. Amaçlar: Çalışmamızda inflamatuvar barsak hastalığı (İBH) vakalarında, serum sRAGE düzeylerinin bu hastalarda farklı klinik ve laboratuvar hastalık aktivite modelleri ile ilişkili bir biyobelirteç olup olamayacağını araştırdık. Yöntemler: Bu vaka kontrol çalışmasına 77 ülseratif kolit (ÜK) hastası (51 erkek ve 26 kadın), 49 Crohn hastalığı (CH) vakası (33 erkek ve 16 kadın) ile 54 sağlıklı kontrol (38 erkek ve 16 kadın) dahil edilmiştir. ÜK’de klinik ve endoskopik aktivite değerendirmesi için Mayo Klinik Skorlama (MKS) sistemi kullanıldı. UK hastalarının histolojik aktivite indeksi (HAİ) Truelove ve Richards yöntemi ile belirlendi. CH klinik aktivitesi için Crohn hastalığı aktivite indeksi (CHAİ) kullanıldı. Bulgular: Medyan sRAGE düzeyleri ÜK hastalarında kontrol grubuna göre düşük bulundu [911.17 ng/L (322.91-1682.19 ve 1420.96 ng/L (816.68-2320.08), sırasıyla, p=0.008)]. CH'li vakalar ile diğer gruplar arasında anlamlı fark yoktu. ÜK hastalarının MKS ve HAİ değerleri ile serum sRAGE konsantrasyonları arasında negatif korelasyon saptandı (rho=-0,610, p<0.001 ve rho=-0,742 sırasıyla, p<0.001). Klinik olarak remisyondaki CH vakaları, aktif hastalığı olanlardan daha yüksek sRAGE değerlerine sahipti [1720.42 ng/L (1005.68-2414.41) ve 923.36 ng/L (601.61-1361.22) sırasıyla, p=0.002]. Tedavi altındaki CH vakalarının sRAGE değerleri, herhangi bir tedavi almayanlardan daha yüksekti [1361.22 ng/L (821.26-1944.2) ve 879.38 ng/L (601.61-1239.41) sırasıyla, p=0.033]. Sonuç: Serum sRAGE, ÜK 'in klinik ve laboratuvar özelliklerinin tespiti için yardımcı bir biyobelirteç olabilir.

Serum-soluble receptor for advanced glycation end-products values might have diagnostic and prognostic significances in ulcerative colitis

Aims: There is evidence of anti-inflammatory qualities associated with a soluble receptor for advanced glycation end products (sRAGE). We aimed to evaluate whether serum sRAGE levels of patients with inflammatory bowel diseases (IBDs) could serve as a biomarker by utilizing several clinical and laboratory models of disease activity for these individuals. Methods: This case-control study included 77 ulcerative colitis (UC) patients (51 males and 26 females), 49 Crohn’s disease (CD) patients (33 males and 16 females) and 54 healthy controls (38 males and 16 females). In UC, the UC Mayo Clinical Scoring system (MCS) was used for the clinical and endoscopic features. The histological activity index (HAI) of UC patients was determined by Truelove and Richards method. The Crohn's disease activity index (CDAI) was utilized for CD patients. Results: In comparison to the control group, the median sRAGE concentrations in UC patients were significantly lower. [911.17 ng/L (322.91-1682.19 vs 1420.96 ng/L (816.68-2320.08), respectively, p=0.008)]. The patients with CD did not significantly differ from the other groups. The MCS and HAI values of UC patients negatively correlated to the serum sRAGE values (rho=-0,610, p<0.001 vs rho=-0,742 respectively, p<0.001). CD patients in remission had higher sRAGE values than patients having active disease [1720.42 ng/L (1005.68-2414.41) vs. 923.36 ng/L (601.61-1361.22 respectively, p=0.002]. CD patients under treatment had higher sRAGE values than patients without any treatment [1361.22 ng/L (821.26-1944.2) vs. 879.38 ng/L (601.61-1239.41) respectively, p=0.033] Conclusion: Serum sRAGE might be an auxiliary biomarker for the clinical and laboratory traits of UC.

Keywords:

Ulcerative colitis, receptor, advanced glycation end-products.,

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Dong H, Zhang Y, Huang Y, Deng H. Pathophysiology of RAGE in inflammatory diseases. Front Immunol. 2022;13:931473. doi: 10.3389/fimmu.2022.931473.
Yue Q, Song Y, Liu Z, Zhang L, Yang L, Li J. Receptor for advanced glycation end products (RAGE): a pivotal hub in immune diseases. Molecules. 2022;27(15):4922. doi: 10.3390/molecules27154922.
Erusalimsky JD. The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes. Redox Biol. 2021;42:101958. doi:10.1016/j.redox.2021.101958.
Vella V, Lappano R, Bonavita E,et al. Insulin/IGF axis and the Receptor for advanced glycation end products: role in meta-inflammation and potential in cancer therapy. Endocr Rev. 2023;44(4):693-723. doi: 10.1210/endrev/bnad005.
Garza-Campos A, Prieto-Correa JR, Domínguez-Rosales JA, Hernández-Nazará ZH. Implications of receptor for advanced glycation end products for progression from obesity to diabetes and from diabetes to cancer. World J Diabetes. 2023;14(7):977-994. doi: 10.4239/wjd. v14.i7.977.
Lou A, Wang L, Lai W, et al. Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway. Bone Joint Res. 2021;10(4):259-268. doi: 10.1302/2046-3758.104.
Meijer B, Hoskin T, Ashcroft A, et al. Total soluble and endogenous secretory receptor for advanced glycation endproducts (RAGE) in IBD. J Crohns Colitis. 2014;8(6):513-520. doi: 10.1016/j. crohns.2013.11.004.
Ciccocioppo R, Imbesi V, Betti E, et al. The circulating level of soluble receptor for advanced glycation end products displays different patterns in ulcerative colitis and Crohn's disease: a cross-sectional study. Dig Dis Sci. 2015;60(8):2327-2337. doi:10.1007/s10620-015-3619-7.
Yilmaz Y, Yonal O, Eren F, Atug O, Hamzaoglu HO. Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity. J Crohns Colitis. 2011;5(5):402-406. doi: 10.1016/j.crohns.2011.03.011.
Bramhall M, Rich K, Chakraborty A, et al. Differential expression of soluble receptor for advanced glycation end-products in mice susceptible or resistant to chronic colitis. Inflamm Bowel Dis. 2020;26(3):360-368. doi:10.1093/ibd/izz311.
Cabrera-García AI, Protschka M, Alber G, et al. Dysregulation of gastrointestinal RAGE (receptor for advanced glycation end products) expression in dogs with chronic inflammatory enteropathy. Vet Immunol Immunopathol. 2021;234:110216. doi: 10.1016/j.vetimm.2021.110216.
Ciccocioppo R, Vanoli A, Klersy C, et al. Role of the advanced glycation end products receptor in Crohn's disease inflammation. World J Gastroenterol. 2013;19(45):8269-8281. doi: 10.3748/wjg. v19.i45.8269.
Body-Malapel M, Djouina M, Waxin C, 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):468-478. doi:10.1038/s41385-018-0119-z.
Steinsbø Ø, Carlsen A, Aasprong OG, et al. Histologic healing and factors associated with complete remission following conventional treatment in ulcerative colitis. Therap Adv Gastroenterol. 2022;15:17562848221140659. doi:10.1177/17562848221140659.
Kozlyuk N, Gilston BA, Salay LE, et al. A fragment-based approach to discovery of receptor for advanced glycation end products inhibitors. Proteins. 2021;89(11):1399-1412. doi: 10.1002/prot.26162.
Koerich S, Parreira GM, de Almeida DL, Vieira RP, de Oliveira ACP. Receptors for advanced glycation end products (RAGE): promising targets aiming at the treatment of neurodegenerative conditions. Curr Neuropharmacol. 2023;21(2):219-234. doi: 10.21 74/1570159X20666220922153903.
Truelove SC, Richards WC. Biopsy studies in ulcerative colitis. Br Med J. 1956;1(4979):1315-1318. doi:10.1136/bmj.1.4979.1315.
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):1625-1629. doi:10.1056/NEJM198712243172603.
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):439-444.
Silverberg MS, Satsangi J, Ahmad T, 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.
Fekete JT, Győrffy B. ROC plot.org: Validating predictive biomarkers of chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,104 breast cancer patients. Int J Cancer. 2019;145(11):3140-3151. doi: 10.1002/ijc.32369.
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. doi:10.3389/fmed.2021.679264.
Küçük İ, Tanoğlu A, Öncü K, et al. Immunohistochemical activity of prohibitin-2 and stomatin-like protein-2 in patients with ulcerative colitis. Turk J Gastroenterol. 2016;27(3):233-238. doi: 10.5152/tjg.2016.15460.
Kekilli M, Tanoğlu A, Karaahmet F, et al. Midkine level may be used as a noninvasive biomarker in Crohn’s disease. Turk J Med Sci. 2020;50(2):324-329. doi: 10.3906/sag-1904-167.
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.
Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut. 1998;43:29-32.
Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ. 1989;298:82-86.
Harvey RF, Bradshaw JM. A simple index of Crohn's-disease activity. Lancet. 1980;1(8167):514.
Daperno MD, Haens G, VanAssche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60:505-512.
D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114(2):262-267. doi: 10.1016/s0016-5085(98)70476-7.
Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Löfberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000;47(3):404-409. doi: 10.1136/gut.47.3.404.
Murray J, Kok KB, Ayling RM. Fecal calprotectin in gastrointestinal disease. Clin Chem. 2023;69(7):699-710. doi: 10.1093/clinchem/hvad051.
Shi JT, Chen N, Xu J, et al. Diagnostic accuracy of fecal calprotectin for predicting relapse in inflammatory bowel disease: a meta-analysis. J Clin Med. 2023;12(3):1206. doi: 10.3390/jcm12031206.