Barrier proteins and eosinophilic esophagitis in children: the role of E-cadherin and filaggrin
Main Article Content
Keywords
Barrier, children, E-cadherin, eosinophilic esophagitis, filaggrin, proteins
Abstract
This study aimed to assess the protein expression of E-cadherin and filaggrin (FLG) in the oesophagus of paediatric and adolescent patients diagnosed with eosinophilic esophagitis (EoE). It is a cross-sectional study conducted with 24 patients with EoE and 17 control patients, from June 2015 to June 2018. The histological analyses were performed by a trained pathologist. The protein expression of E-cadherin and FLG in oesophageal biopsy fragments was determined using an immunohistochemical technique. The epidemiological data were retrieved from medical records. There were no statistical differences in age and sex between case-patients and control patients. Food allergy was significantly higher in patients with EoE, as was the number of eosinophils present in the oesophageal biopsy materials. The immunohistochemical studies did not indicate FLG expression in any patient from the two groups. E-cadherin showed significantly reduced expression in patients with EoE. We concluded that FLG did not seem to play an important role in the mucosal alteration in EoE and that E-cadherin under expression could be a promising marker of epithelial damage in these patients.
References
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27. Krishnan U, Lijuan C, Andrew GJ, Rothenberg ME, Wen T. Analysis of eosinophilic esophagitis in children with repaired congenital esophageal atresia. J Allergy Clin Immunol. 2019; 143(4):1455–64. 10.1016/j.jaci.2018.08.040
2. Davis BP. Pathophysiology of Eosinophilic esophagitis. Clin Rev Allergy Immunol. 2018;55(1):9–42. 10.1053/j.gastro.2017.06.065
3. Lucendo AJ, Molina-Infante J, Arias Á, Arnim U, Bredenoord AJ, Bussmann C. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017;5(3):335–58. 10.1177/2050640616689525
4. Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, et al., Updated international consensus diagnostic criteria for Eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology. 2018;155(4):1022–33. 10.1053/j.gastro.2018.07.009
5. Schleimer R, Berdnikovs S. Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases. J Allergy Clin Immunol. 2017;139(6):1752–61. 10.1016/j.jaci.2017.04.010
6. Rochman M, Nurit PA, Rothemberg ME. Epithelial origin of eosinophilic esophagitis. J Allergy Clin Immunol. 2018; 14(1):10–23. 10.1016/j.jaci.2018.05.008
7. Chen Y, Merzdorf C, Paul DL, Goodenough DA. COOH terminus of occludin is required for tight junction barrier function in early Xenopus embryos. J Cell Biol. 1997;138(4):891–99. 10.1083/jcb.138.4.891
8. Palmer CN, Irvine AD, Kwiatkowski AT, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441–46. 10.1038/ng1767
9. Abdulnour SM, Al-Tawil Y, Gyftopoulos AA, Brown KL, Hansen M, Butcher KF. Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis. Clin Immunol. 2013;48(2):265–78. 10.1016/j.clim.2013.05.004
10. Takeichi M. Morphogenetic roles of classic cadherins. Curr Opin Cell Biol. 1995;7: 619–27. 10.1016/0955-0674(95)80102-2
11. Leckband D, Prakasam A. Mechanism and dynamics of cadherin adhesion. Annu Rev Biomed Eng. 2006;8: 259–287. 10.1146/annurev.bioeng.8.061505.095753
12. Hirano I, Chan E, Rank M, Sharaf R, Stollman N, Stukus D, et al. AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Gastroenterology. 2020;158:1776–86. 10.1053/j.gastro.2020.02.038
13. Ferreira CT, Vieira MC, Furuta G, Barros FCLF, Chehade M. Eosinophilic esophagitis-Where are we today? J Pediatr. 2019;95(3):275–81. 10.1016/j.jped.2018.06.012
14. Tan HT, Ellis JA, Koplin JJ, Matheson MC, Gurrin LC, Lowe AJ, et al. Filaggrin loss-of-function mutations do not predict food allergy over and above the risk of food sensitization among infants. J Allergy Clin Immunol. 2012;130(5):1211–13. 10.1016/j.jaci.2012.07.022
15. Palmer CN, Irvine AD, Kwiatkowski AT, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441–46. 10.1038/ng1767
16. Blanchard C, Stucke EM, Burwinkel K, Caldwell JM, Collins MH, Ahrens A, et al. Coordinate interection between IL-13 and epitelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010;184(7):4033–41. 10.4049/jimmunol.0903069
17. Simon D, Radonjic S, Straumann A, Yousefi S, Simon HU. Active Eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation. Allergy. 2015;70(4):443–52. 10.1111/all.12570
18. Osawa R, Akiyama M, Shimizu H. Filaggrin gene defects and the risk of developing allergic disorders. Allergol Int. 2011;60(1):1–9. 10.2332/allergolint.10-RAI-0270
19. Benedetto AD, Qualia CM, Baroody FM, Beck LA. Filaggrin expression in oral, nasal, and Esophageal Mucosa. J Invest Dermatol. 2008;128(6):1594–97. 10.1038/sj.jid.5701208
20. Grunwald GB. The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules. Curr Opin Cell Biol. 1993;5:797–80. 10.1016/0955-0674(93)90028-o
21. Bajpai S, Correia J, Fenf Y, Figueireso J, Sun SX, Longmore GD, et al.{alpha}-Catenin mediates initial E-cadherin dependent cell–cell recognition and subsequent bond strengthening. Proc Natl Acad Sci USA. 2008;105:18331–36. 10.1073/pnas.0806783105
22. Chan AO. E-cadherin in gastric cancer. World J Gastroenterol. 2006;12(2):199–203. 10.3748/wjg.v12.i2.199
23. Jeanes A, Gottardi CJ, Yap AS. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene. 2008;27:6920–29. 10.1038/onc.2008.343
24. Nawijn MC, Hackett TL, Postma DS, van Oosterhout AJ, Heijink IH. E-cadherin: gatekeeper of airway mucosa and allergic sensitization. Trends Immunol. 2011; 32(6):248–55. 10.1016/j.it.2011.03.004
25. Lee HJ, Kim B, Im NR, Lee DY, Kim HK, Lee SH, et al. Decreased expression. Of E-cadherin and ZO-1 in the nasal mucosa of patients with allergic rhinitis. Am J Rhinol Allergy. 2016;30:173–78. 10.2500/ajra.2016.30.4295
26. Nápolis ACN, Alves FA, Rezende ERMA, Segundo GRS. Esophageal eosinophilia in pediatric patients with cerebral palsy. Einstein. 2015;13(2):232–37. 10.1590/S1679-45082015AO3266
27. Krishnan U, Lijuan C, Andrew GJ, Rothenberg ME, Wen T. Analysis of eosinophilic esophagitis in children with repaired congenital esophageal atresia. J Allergy Clin Immunol. 2019; 143(4):1455–64. 10.1016/j.jaci.2018.08.040
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Jul 1, 2022
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