The diagnostic value of calcium binding protein S100A8/A9 and S100A12 in acute pancreatitis

Abstract

Background: S100A8/A9 and S100A12 which are the major calcium-binding proinflammatory proteins secreted by granulocytes, has been proposed to be related to distinct disease states of inflammatory origin. This study aims to explore the circulating levels of S100A8/A9 and S100A12 in acute pancreatitis (AP) and reveal their relationship with conventional inflammatory markers. Material and Method: Serum S100A8/A9 and S100A12 were determined in AP patients (male/female: 17/13) by using a specific enzyme-linked immunosorbent assay (ELISA) method at both onset and remission and in 30 healthy controls (male/female: 17/13). Results: Significantly higher S100A8/A9 and S100A12 levels were found in AP patients compared to healthy controls (p<0.001). Circulating levels of S100A8/9, S100A12 and C-reactive protein (CRP) were found to be elevated in AP patients at disease onset compared with remission. The correlation analysis demonstrated a significant association between S100A8/A9 and S100A12 (r=0.366, p=0.047). The cut-off level for S100A8/A9 for detecting AP was ≥54.4 ng/ml with a sensitivity and specificity of 96.7% and 73.3% (AUC: 0.958). The optimum cut-off level for S100A12 for detecting AP was ≥350.25 ng/ml with a sensitivity and specificity of 73.3% and 76.7% (AUC: 0.752) respectively. Conclusion: Circulating S100A8/A9 and S100A12 levels were found to be elevated in AP patients. Both of these markers might serve as an additional tool in the diagnostic workup in AP since S100A8/A9 and S100A12 were significantly correlated with CRP.

Keywords

• Acute pancreatitis
• S100A8/A9
• S100A12
• CRP
• inflammation

Project Number

THD-2020-3255

References

1. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 2013; 144: 1252-61.
2. Gumaste VV. Diagnostic tests for acute pancreatitis. Gastroenterologist. 1994; 2: 119-30.
3. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 2004; 50: 3762-71
4. Manolakis AC, Kapsoritakis AN, Georgoulias P, et al. Moderate performance of serum S100A12, in distinguishing inflammatory bowel disease from irritable bowel syndrome. BMC Gastroenterol 2010; 10: 118.
5. Liu K, Pichichero ME. Clinical significance of serum S100A12 in acute otitis media in young children. Pediatr Infect Dis J 2012; 3: e56-8.
6. Gohar F, Anink J, Moncrieffe H, et al. S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis. J Rheumatol 2018; 45: 547-54
7. Hinze CH, Foell D, Johnson AL, et al. Serum S100A8/A9 and S100A12 Levels in children with polyarticular forms of juvenile idiopathic arthritis: relationship to maintenance of clinically inactive disease during anti-tumor necrosis factor therapy and occurrence of disease flare after discontinuation of therapy. Arthritis Rheumatol 2019; 71: 451-9.
8. Prystupa A, Kiciński P, Luchowska-Kocot D, et al. Analysis of novel serum markers of fibrosis and angiogenesis in patients with alcoholic liver cirrhosis. Ann Agric Environ Med 2020; 27: 568-73.

9. Şumnu Ş, Mehtap Ö, Mersin S, et al. Serum calprotectin (S100A8/A9) levels as a new potential biomarker of treatment response in Hodgkin lymphoma. Int J Lab Hematol 202; 43: 638-44
10. Müller I, Vogl T, Kühl U, et al. Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis. ESC Heart Fail 2020; 7: 1442-51.
11. Banks PA, Bollen TL, Dervenis C, et al. Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013; 62: 102-11.
12. van Dijk SM, Hallensleben NDL, van Santvoort HC, et al. Acute pancreatitis: recent advances through randomised trials. Gut 2017; 66: 2024-32.
13. Vatansever S, Doğru R, Pakoz ZB, Genç H, Ünsal B. Evaluation of laboratory findings and mortality in elderly patients with acute biliary pancreatitis. Sisli Etfal Hastan Tip Bul 2018; 52: 274-8.
14. Ünal Çetin E, Kamiş F, Çetin AU, Beyazit Y, Kekilli M. Serum chitotriosidase and YKL-40 in acute pancreatitis: Reliability as prognostic marker for disease severity and correlation with inflammatory markers. Turk J Med Sci 2021; 51: 3038-46.
15. Gezer NS, Bengi G, Baran A, et al. Comparison of radiological scoring systems, clinical scores, neutrophil-lymphocyte ratio and serum C-reactive protein level for severity and mortality in acute pancreatitis. Rev Assoc Med Bras (1992) 2020; 66: 762-70.
16. Rasslan R, Novo FDCF, Bitran A, Utiyama EM, Rasslan S. Management of infected pancreatic necrosis: state of the art. Rev Col Bras Cir 2017; 44: 521-9.
17. Korkmaz H, Tabur S, Savaş E, et al. Evaluation of serum S100A8/S100A9 levels in patients with autoimmune thyroid diseases. Balkan Med J 2016; 33: 547-51.
18. van Bon L, Cossu M, Loof A, et al. Proteomic analysis of plasma identifies the Toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype. Ann Rheum Dis 2014 A; 73: 1585-9.
19. Kessel C, Lavric M, Weinhage T, et al. Serum biomarkers confirming stable remission in inflammatory bowel disease. Sci Rep 2021; 11: 6690.
20. Türkmenoğlu Y, Güney E, Bezen D, İrdem A, Ertürk B, Dursun H. Evaluation of S100A12 protein levels in children with familial Mediterranean fever. Turk J Med Sci 2021; 51: 1396-1405.
21. van den Bos C, Roth J, Koch HG, Hartmann M, Sorg C. Phosphorylation of MRP14, an S100 protein expressed during monocytic differentiation, modulates Ca(2+)-dependent translocation from cytoplasm to membranes and cytoskeleton. J Immunol. 1996; 156: 1247-54
22. Hu W, Lin C. S100a8 silencing attenuates inflammation, oxidative stress and apoptosis in BV2 cells induced by oxygen glucose deprivation and reoxygenation by upregulating GAB1 expression. Mol Med Rep 2021; 23: 64.
23. El Gammal AT, Sturm JH, Pinnschmidt HO, et al. Protein S100A8/A9: A potential new biomarker for pancreatic diseases. Int J Clin Endocrinol Metab 2017;3: 23-8.
24. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 2004; 50:3762-71.
25. Cai J, Han T, Nie C, et al. Biomarkers of oxidation stress, inflammation, necrosis and apoptosis are associated with hepatitis B-related acute-on-chronic liver failure. Clin Res Hepatol Gastroenterol 2016; 40: 41-50.
26. Aljaberi N, Tronconi E, Schulert G, et al. The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis. Pediatr Rheumatol Online J 2020; 18: 7
27. Feng Z, Yinchu Z, Yinsheng S, et al. Potential effects of calcium binding protein S100A12 on severity evaluation and curative effect of severe acute pancreatitis. Inflammation 2015; 38: 290-7.