Research Article
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Fecal S100A12 as a Biomarker in Behcet’s Disease

Year 2021, , 616 - 624, 01.07.2021
https://doi.org/10.31067/acusaglik.928333

Abstract

Background: Gastroinestinal involvement in Behcet’s disease impacts morbidity and mortality. The diagnosis of gastrointestinal disease requires comprehensive evaluation with endoscopic and radiologic examinations which is costly and impractical. A biomarker is essential for non-invasive detection. Fecal S100A12 is an established biomarker in gastrointestinal inflammatory diseases and its serum levels are known to increase in Behcet’s Disease. In this study, we aimed to tests fecal S100A12 levels in Behcet’s patients, its relation with gastrointestinal symptoms to its potential as a biomarker in gastrointestinal involvement.

Methods: We prospectively enrolled 48 cases of Behcet’s disease patients fulfilling International Study Group criteria from a university hospital. We excluded patients with other autoimmune conditions, active or recent infection, using NSAIDs and antibiotics. Control group was selected from volunteers who had applied to the rheumatology outpatient clinic. Patients with BD were categorized into 5 groups according to organ involvement. Also we evaluated and recorded disease activity with the BDCAF 2006. Fecal S100A12, fecal calprotectin and acute phase reactants were also collected.

Results: Fecal calprotectin levels were six-fold higher in BD than controls (p<0.0001). Fecal S100A12 was also two-fold higher albeit without statistical significance (p=0.132). Fecal calprotectin and fecal S100A12 levels were positively correlated (r:0.530, p<0.0001). Both fecal calprotectin (138.1 μg/g vs 50.1 μg/g, p=0.006).) and fecal S100A12 (48.3 ng/mL vs 19.4 ng/mL, p=0.023) were higher in Behçet's patients with gastrointestinal symptoms compared to those without. Fecal calprotectin and fecal S100A12 levels were not correlated with total BDCAF score, CRP and ESR levels.
Conclusion: Fecal S100A12 is correlated with fecal calprotectin and higher in Behcet’s patients with gastrointestinal involvement. This is the first study of fecal S100A12 in Behcet’s disease and its potential use in Behcet’s disease patients with gastrointestinal symptoms.

Supporting Institution

Hacettepe University Scientific Research Project Fund.

Project Number

THD-2017-13174

References

  • 1. Hatemi G, Yazici Y, Yazici H. Behcet's syndrome. Rheum Dis Clin North Am. 2013;39(2):245-61.
  • 2. Sota J, Vitale A, Rigante D, Orlando I, Lucherini OM, Simpatico A, et al. Correlation of Serum Amyloid-A Levels, Clinical Manifestations, Treatment, and Disease Activity in Patients with Behcet's Disease. Isr Med Assoc J. 2018;20(8):517-21.
  • 3. Melikoglu M, Topkarci Z. Is there a relation between clinical disease activity and acute phase response in Behcet's disease? Int J Dermatol. 2014;53(2):250-4.
  • 4. Lawton G, Bhakta BB, Chamberlain MA, Tennant A. The Behcet's disease activity index. Rheumatology (Oxford). 2004;43(1):73-8.
  • 5. Bhakta BB, Brennan P, James TE, Chamberlain MA, Noble BA, Silman AJ. Behcet's disease: evaluation of a new instrument to measure clinical activity. Rheumatology (Oxford). 1999;38(8):728-33.
  • 6. Hamuryudan V, Fresko I, Direskeneli H, Tenant MJ, Yurdakul S, Akoglu T, et al. Evaluation of the Turkish translation of a disease activity form for Behcet's syndrome. Rheumatology (Oxford). 1999;38(8):734-6.
  • 7. Kopec-Medrek M, Widuchowska M, Kucharz EJ. Calprotectin in rheumatic diseases: a review. Reumatologia. 2016;54(6):306-9.
  • 8. Manolakis AC, Kapsoritakis AN, Tiaka EK, Potamianos SP. Calprotectin, calgranulin C, and other members of the s100 protein family in inflammatory bowel disease. Dig Dis Sci. 2011;56(6):1601-11.
  • 9. Heida A, Van de Vijver E, van Ravenzwaaij D, Van Biervliet S, Hummel TZ, Yuksel Z, et al. Predicting inflammatory bowel disease in children with abdominal pain and diarrhoea: calgranulin-C versus calprotectin stool tests. Arch Dis Child. 2018;103(6):565-71.
  • 10. Johne B, Fagerhol MK, Lyberg T, Prydz H, Brandtzaeg P, Naess-Andresen CF, et al. Functional and clinical aspects of the myelomonocyte protein calprotectin. Mol Pathol. 1997;50(3):113-23.
  • 11. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum. 2004;50(12):3762-71.
  • 12. Pietzsch J, Hoppmann S. Human S100A12: a novel key player in inflammation? Amino Acids. 2009;36(3):381-9.
  • 13. Han EC, Cho SB, Ahn KJ, Oh SH, Kim J, Kim DS, et al. Expression of Pro-inflammatory Protein S100A12 (EN-RAGE) in Behcet's Disease and Its Association with Disease Activity: A Pilot Study. Ann Dermatol. 2011;23(3):313-20.
  • 14. Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet's disease: a review. World J Gastroenterol. 2015;21(13):3801-12.
  • 15. Oktayoglu P, Mete N, Caglayan M, Bozkurt M, Bozan T, Em S, et al. Elevated serum levels of calprotectin (MRP8/MRP14) in patients with Behcet's disease and its association with disease activity and quality of life. Scand J Clin Lab Invest. 2015;75(2):106-12.
  • 16. Kim DH, Park Y, Kim B, Kim SW, Park SJ, Hong SP, et al. Fecal calprotectin as a non-invasive biomarker for intestinal involvement of Behcet's disease. J Gastroenterol Hepatol. 2017;32(3):595-601.
  • 17. Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet. 1990;335(8697):1078-80.
  • 18. Fauny M, D’amico F, Bonovas S, Netter P, Danese S, Loeuille D, et al. Faecal calprotectin for the diagnosis of bowel inflammation in patients with rheumatological diseases: a systematic review. Journal of Crohn's and Colitis. 2020;14(5):688-93.
  • 19. Hamdulay S, Cheent K, Ghosh C, Stocks J, Ghosh S, Haskard D. Wireless capsule endoscopy in the investigation of intestinal Behçet's syndrome. Rheumatology. 2008;47(8):1231-4.
  • 20. Neves FS, Fylyk SN, Lage LV, Ishioka S, Goldenstein-Schainberg C, Sakai P, et al. Behçet’s disease: clinical value of the video capsule endoscopy for small intestine examination. Rheumatology international. 2009;29(5):601-3.
  • 21. Choi CH, Kim TI, Kim BC, Shin SJ, Lee SK, Kim WH, et al. Anti-Saccharomyces cerevisiae antibody in intestinal Behçet’s disease patients: relation to clinical course. Diseases of the colon & rectum. 2006;49(12):1849-59.
  • 22. Shin SJ, Kim BC, Kim TI, Lee SK, Lee KH, Kim WH. Anti-alpha-enolase antibody as a serologic marker and its correlation with disease severity in intestinal Behçet’s disease. Digestive diseases and sciences. 2011;56(3):812-8.
  • 23. Lee HW, Chung SH, Moon CM, Che X, Kim SW, Park SJ, et al. The correlation of serum IL-12B expression with disease activity in patients with inflammatory bowel disease. Medicine. 2016;95(23).
  • 24. Hayasaki N, Ito M, Suzuki T, Ina K, Ando T, Kusugami K, et al. Neutrophilic phlebitis is characteristic of intestinal Behçet's disease and simple ulcer syndrome. Histopathology. 2004;45(4):377-83.
  • 25. Carvalho A, Lu J, Francis JD, Moore RE, Haley KP, Doster RS, et al. S100A12 in Digestive Diseases and Health: A Scoping Review. Gastroenterology Research and Practice. 2020;2020.
Year 2021, , 616 - 624, 01.07.2021
https://doi.org/10.31067/acusaglik.928333

Abstract

Project Number

THD-2017-13174

References

  • 1. Hatemi G, Yazici Y, Yazici H. Behcet's syndrome. Rheum Dis Clin North Am. 2013;39(2):245-61.
  • 2. Sota J, Vitale A, Rigante D, Orlando I, Lucherini OM, Simpatico A, et al. Correlation of Serum Amyloid-A Levels, Clinical Manifestations, Treatment, and Disease Activity in Patients with Behcet's Disease. Isr Med Assoc J. 2018;20(8):517-21.
  • 3. Melikoglu M, Topkarci Z. Is there a relation between clinical disease activity and acute phase response in Behcet's disease? Int J Dermatol. 2014;53(2):250-4.
  • 4. Lawton G, Bhakta BB, Chamberlain MA, Tennant A. The Behcet's disease activity index. Rheumatology (Oxford). 2004;43(1):73-8.
  • 5. Bhakta BB, Brennan P, James TE, Chamberlain MA, Noble BA, Silman AJ. Behcet's disease: evaluation of a new instrument to measure clinical activity. Rheumatology (Oxford). 1999;38(8):728-33.
  • 6. Hamuryudan V, Fresko I, Direskeneli H, Tenant MJ, Yurdakul S, Akoglu T, et al. Evaluation of the Turkish translation of a disease activity form for Behcet's syndrome. Rheumatology (Oxford). 1999;38(8):734-6.
  • 7. Kopec-Medrek M, Widuchowska M, Kucharz EJ. Calprotectin in rheumatic diseases: a review. Reumatologia. 2016;54(6):306-9.
  • 8. Manolakis AC, Kapsoritakis AN, Tiaka EK, Potamianos SP. Calprotectin, calgranulin C, and other members of the s100 protein family in inflammatory bowel disease. Dig Dis Sci. 2011;56(6):1601-11.
  • 9. Heida A, Van de Vijver E, van Ravenzwaaij D, Van Biervliet S, Hummel TZ, Yuksel Z, et al. Predicting inflammatory bowel disease in children with abdominal pain and diarrhoea: calgranulin-C versus calprotectin stool tests. Arch Dis Child. 2018;103(6):565-71.
  • 10. Johne B, Fagerhol MK, Lyberg T, Prydz H, Brandtzaeg P, Naess-Andresen CF, et al. Functional and clinical aspects of the myelomonocyte protein calprotectin. Mol Pathol. 1997;50(3):113-23.
  • 11. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum. 2004;50(12):3762-71.
  • 12. Pietzsch J, Hoppmann S. Human S100A12: a novel key player in inflammation? Amino Acids. 2009;36(3):381-9.
  • 13. Han EC, Cho SB, Ahn KJ, Oh SH, Kim J, Kim DS, et al. Expression of Pro-inflammatory Protein S100A12 (EN-RAGE) in Behcet's Disease and Its Association with Disease Activity: A Pilot Study. Ann Dermatol. 2011;23(3):313-20.
  • 14. Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet's disease: a review. World J Gastroenterol. 2015;21(13):3801-12.
  • 15. Oktayoglu P, Mete N, Caglayan M, Bozkurt M, Bozan T, Em S, et al. Elevated serum levels of calprotectin (MRP8/MRP14) in patients with Behcet's disease and its association with disease activity and quality of life. Scand J Clin Lab Invest. 2015;75(2):106-12.
  • 16. Kim DH, Park Y, Kim B, Kim SW, Park SJ, Hong SP, et al. Fecal calprotectin as a non-invasive biomarker for intestinal involvement of Behcet's disease. J Gastroenterol Hepatol. 2017;32(3):595-601.
  • 17. Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet. 1990;335(8697):1078-80.
  • 18. Fauny M, D’amico F, Bonovas S, Netter P, Danese S, Loeuille D, et al. Faecal calprotectin for the diagnosis of bowel inflammation in patients with rheumatological diseases: a systematic review. Journal of Crohn's and Colitis. 2020;14(5):688-93.
  • 19. Hamdulay S, Cheent K, Ghosh C, Stocks J, Ghosh S, Haskard D. Wireless capsule endoscopy in the investigation of intestinal Behçet's syndrome. Rheumatology. 2008;47(8):1231-4.
  • 20. Neves FS, Fylyk SN, Lage LV, Ishioka S, Goldenstein-Schainberg C, Sakai P, et al. Behçet’s disease: clinical value of the video capsule endoscopy for small intestine examination. Rheumatology international. 2009;29(5):601-3.
  • 21. Choi CH, Kim TI, Kim BC, Shin SJ, Lee SK, Kim WH, et al. Anti-Saccharomyces cerevisiae antibody in intestinal Behçet’s disease patients: relation to clinical course. Diseases of the colon & rectum. 2006;49(12):1849-59.
  • 22. Shin SJ, Kim BC, Kim TI, Lee SK, Lee KH, Kim WH. Anti-alpha-enolase antibody as a serologic marker and its correlation with disease severity in intestinal Behçet’s disease. Digestive diseases and sciences. 2011;56(3):812-8.
  • 23. Lee HW, Chung SH, Moon CM, Che X, Kim SW, Park SJ, et al. The correlation of serum IL-12B expression with disease activity in patients with inflammatory bowel disease. Medicine. 2016;95(23).
  • 24. Hayasaki N, Ito M, Suzuki T, Ina K, Ando T, Kusugami K, et al. Neutrophilic phlebitis is characteristic of intestinal Behçet's disease and simple ulcer syndrome. Histopathology. 2004;45(4):377-83.
  • 25. Carvalho A, Lu J, Francis JD, Moore RE, Haley KP, Doster RS, et al. S100A12 in Digestive Diseases and Health: A Scoping Review. Gastroenterology Research and Practice. 2020;2020.
There are 25 citations in total.

Details

Primary Language English
Subjects Gastroenterology and Hepatology, Rheumatology and Arthritis
Journal Section Research Articles
Authors

Cem Şimşek 0000-0002-7037-5233

Berkan Armağan 0000-0003-4409-059X

Benazir Hymabaccus 0000-0001-5415-218X

Alper Sarı 0000-0002-3286-0940

Abdulsamet Erden 0000-0001-5415-218X

Levent Kılıç 0000-0003-1064-9690

Ali Akdoğan 0000-0002-8064-0766

Project Number THD-2017-13174
Publication Date July 1, 2021
Submission Date April 26, 2021
Published in Issue Year 2021

Cite

EndNote Şimşek C, Armağan B, Hymabaccus B, Sarı A, Erden A, Kılıç L, Akdoğan A (July 1, 2021) Fecal S100A12 as a Biomarker in Behcet’s Disease. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 12 3 616–624.