Non-invasive biomarkers of eosinophilic esophagitis

Non-invasive biomarkers of eosinophilic esophagitis

Authors

  • Martina Votto Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Maria De Filippo Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Riccardo Castagnoli Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy https://orcid.org/0000-0003-0029-9383
  • Francesco Delle Cave Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Francesca Giffoni Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Viola Santi Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Marta Vergani Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Carlo Caffarelli Pediatric Clinic, Department of Medicine and Surgery, Unversity of Parma, Parma, Italy
  • Mara De Amici Immuno-Allergology Laboratory, Clinical Chemistry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Gian Luigi Marseglia Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
  • Amelia Licari Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy https://orcid.org/0000-0002-1773-6482

Keywords:

Eosinophilic esophagitis, Biomarkers, Cytokines, Genes, Atopy

Abstract

Eosinophilic esophagitis (EoE) is an emerging allergen-mediated disease characterized by symptoms of esophageal dysfunction and eosinophilic inflammation. EoE diagnosis requires 15 eosinophils per high power field (eos/HPF) in tissue biopsies endoscopically obtained. The need for several endoscopies to monitoring the disease and the absence of validated non-invasive biomarkers or tools are the main reasons for the significant burden on affected patients and the healthcare system. There is a critical need for non-invasive or minimally invasive biomarkers. In the last years, several efforts have been made to identify potential biomarkers for diagnosing and monitoring the disease that we summarized in this review. The future of EoE is exciting from both a diagnostic and therapeutic standpoint. Further research is required to confirm phenotypes and histological or serological biomarkers to provide a novel endotype classification based on different cytokine or genetic signatures relevant to precision medicine.

References

Licari A, Votto M, D'Auria E, et al. Eosinophilic gastrointestinal diseases in children: a practical review. Curr Pediatr Rev 2020;16:106-114.

Licari A, Votto M, Scudeller L, et al. Epidemiology of nonesophageal eosinophilic gastrointestinal diseases in symptomatic patients: a systematic review and meta-analysis. J Allergy Clin Immunol Pract 2020;8:1994-2003.

Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology 2018;155:1022-1033.

Furuta GT, Katzka DA. Eosinophilic esophagitis. N Engl J Med 2015;373:1640-8.

Dellon ES, Hirano I. Epidemiology and natural history of eosinophilic esophagitis. Gastroenterology 2018;154:319-332.

Votto M, Castagnoli R, De Filippo M, et al. Behavioral issues and quality of life in children with eosinophilic esophagitis. Minerva Pediatr 2020;72:424-432.

FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource. Silver Spring (MD): Food and Drug Administration (US); Bethesda (MD): National Institutes of Health (US), 2016.

Califf RM. Biomarker definitions and their applications. Exp Biol Med (Maywood). 2018;243:213-221.

Rodríguez-Sánchez J, Gómez-Torrijos E, De-la-Santa-Belda E, et al. Effectiveness of serological markers of eosinophil activity in monitoring eosinophilic esophagitis. Rev Esp Enferm Dig 2013;105:462-7.

Wechsler JB, Ackerman SJ, Chehade M, et al. Non-invasive biomarkers identify eosinophilic esophagitis: a prospective longitudinal study in children. Allergy 2021. Epub ahead of print.

Min SB, Nylund CM, Baker TP, et al. Longitudinal evaluation of noninvasive biomarkers for eosinophilic esophagitis. J Clin Gastroenterol 2017;51:127-135.

Nguyen T, Gernez Y, Fuentebella J, et al. Immunophenotyping of peripheral eosinophils demonstrates activation in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2011;53:40-47.

Morris DW, Stucke EM, Martin LJ, et al. Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis. J Allergy Clin Immunol 2016;138:915-918.

Johansson MW, McKernan EM, Fichtinger PS, et al. αIIb-Integrin (CD41) associated with blood eosinophils is a potential biomarker for disease activity in eosinophilic esophagitis. J Allergy Clin Immunol 2020;145:1699-1701.

Schwartz JT, Morris DW, Collins MH, et al. Eosinophil progenitor levels correlate with tissue pathology in pediatric eosinophilic esophagitis. J Allergy Clin Immunol 2019;143:1221-1224.

Henderson A, Magier A, Schwartz JT, et al. Monitoring eosinophilic esophagitis disease activity with blood eosinophil progenitor levels. J Pediatr Gastroenterol Nutr 2020;70:482-488.

Subbarao G, Rosenman MB, Ohnuki L, et al. Exploring potential non-invasive biomarkers in eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr 2011; 53:651–658.

Schlag C, Pfefferkorn S, Brockow K, et al. Serum eosinophil cationic protein is superior to mast cell tryptase as a marker for response to topical corticosteroid therapy in eosinophilic esophagitis. J Clin Gastroenterol 2014;48:600-606.

Doménech Witek J, Jover Cerdà V, Gil Guillén V, et al. Assessing eosinophilic cationic protein as a biomarker for monitoring patients with eosinophilic esophagitis treated with specific exclusion diets. World Allergy Organ J 2017;10:12.

Cengiz C. Serum eosinophilic cationic protein is correlated with food impaction and endoscopic severity in eosinophilic esophagitis. Turk J Gastroenterol 2019;30:345-349.

Wright BL, Ochkur SI, Olson NS, et al. Normalized serum eosinophil peroxidase levels are inversely correlated with esophageal eosinophilia in eosinophilic esophagitis. Dis Esophagus 2018;31:dox139.

Wen T, Stucke EM, Grotjan TM, et al. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology 2013;145:1289-1299.

Lu S, Herzlinger M, Cao W, et al. Utility of 15(S)-HETE as a serological marker for eosinophilic esophagitis. Sci Rep 2018;8:14498.

Dellon ES, Rusin S, Gebhart JH, et al. Utility of a non-invasive serum biomarker panel for diagnosis and monitoring of eosinophilic esophagitis: a prospective study. Am J Gastroenterol 2015;110:821-7.

Dellon ES, Higgins LL, Beitia R, et al. Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis. Aliment Pharmacol Ther 2016;44:189-97.

Capucilli P, Cianferoni A, Grundmeier RW, et al. Comparison of comorbid diagnoses in children with and without eosinophilic esophagitis in a large population. Ann Allergy Asthma Immunol 2018;121:711-716.

Dellon ES, Lin L, Beitia R, et al. Serum autoantibodies against epithelial cell adhesion molecules as disease biomarkers of eosinophilic esophagitis. Clin Exp Allergy 2018;48:343-346.

Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointest Endosc Clin N Am 2008;18:59-71.

Wright BL, Doyle AD, Shim KP, et al. Image analysis of eosinophil peroxidase immunohistochemistry for diagnosis of eosinophilic esophagitis. Dig Dis Sci 2021;66:775-783.

Saffari H, Leiferman KM, Clayton F, et al. Measurement of inflammation in eosinophilic esophagitis using an eosinophil peroxidase assay. Am J Gastroenterol 2016;111:933-939.

Schroeder S, Ochkur SI, Shim KP, et al. Throat-derived eosinophil peroxidase is not a reliable biomarker of pediatric eosinophilic esophagitis. J Allergy Clin Immunol Pract 2017;5:1804-1805.

Peterson KA, Gleich GJ, Limaye NS, et al. Eosinophil granule major basic protein 1 deposition in eosinophilic esophagitis correlates with symptoms independent of eosinophil counts. Dis Esophagus 2019;32:doz055.

Kim GH, Park YS, Jung KW, et al. An increasing trend of eosinophilic esophagitis in Korea and the clinical implication of the biomarkers to determine disease activity and treatment response in eosinophilic esophagitis. J Neurogastroenterol Motil 2019;25:525-533.

Dellon ES, Woosley JT, McGee SJ, et al. Utility of major basic protein, eotaxin-3, and mast cell tryptase staining for prediction of response to topical steroid treatment in eosinophilic esophagitis: analysis of a randomized, double-blind, double dummy clinical trial. Dis Esophagus 2020;33:doaa003.

Dellon ES, Speck O, Woodward K, et al. Markers of eosinophilic inflammation for diagnosis of eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia: a prospective study. Clin Gastroenterol Hepatol 2014;12:2015-2022.

Dellon ES, Chen X, Miller CR, et al. Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. Am J Gastroenterol 2012;107:1503-1511.

Smadi Y, Deb C, Bornstein J, et al. Blind esophageal brushing offers a safe and accurate method to monitor inflammation in children and young adults with eosinophilic esophagitis. Dis Esophagus 2018;31.

Matoso A, Mukkada VA, Lu S, et al. Expression microarray analysis identifies novel epithelial-derived protein markers in eosinophilic esophagitis. Mod Pathol 2013;26:665–676.

Hui Y, Chen S, Lombardo KA, et al. ALOX15 immunohistochemistry aids in the diagnosis of eosinophilic esophagitis on paucieosinophilic biopsies in children. Pediatr Dev Pathol 2017;20:375–380.

Clayton F, Fang JC, Gleich GJ, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology 2014;147:602–609.

Zukerberg L, Mahadevan K, Selig M, et al. Oesophageal intrasquamous IgG4 deposits: an adjunctive marker to distinguish eosinophilic oesophagitis from reflux oesophagitis. Histopathology 2016;68:968–976.

Rosenberg CE, Mingler MK, Caldwell JM, et al. Esophageal IgG4 levels correlate with histopathologic and transcriptomic features in eosinophilic esophagitis. Allergy 2018;73:1892–1901.

Lu TX, Sherrill JD, Wen T, et al. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol 2019;129:1064-1075.

Bhardwaj N, Sena M, Ghaffari G, Ishmael F. MiR-4668 as a novel potential biomarker for eosinophilic esophagitis. Allergy Rhinol (Providence) 2020;11:2152656720953378.

Strisciuglio C, Payne F, Nayak K, et al. Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with eosinophilic esophagitis. Clin Epigenetics 2021;13:81.

Jensen ET, Langefeld CD, Zimmerman KD, et al. Epigenetic methylation in eosinophilic esophagitis: molecular ageing and novel biomarkers for treatment response. Clin Exp Allergy 2020;50:1372-1380.

Votto M, De Filippo M, Licari A, Marseglia A, De Amici M, Marseglia GL. Biological therapies in children and adolescents with severe uncontrolled asthma: a practical review. Biologics 2021;15:133-142.

Leung J, Nguyen-Traxler A, Lee EM, et al. Assessment of fractionated exhaled nitric oxide as a biomarker for the treatment of eosinophilic esophagitis. Allergy Asthma Proc 2012;33:519-524.

Lanz MJ, Guerrero RA, Gonzalez-Vallina R. Measurement of exhaled nitric oxide in the evaluation for eosinophilic esophagitis in children. Ann Allergy Asthma Immunol 2012;109:81-82.

Moye LM, Liu Y, Coarfa C, et al. Plasma urea cycle metabolites may be useful biomarkers in children with eosinophilic esophagitis. Front Pediatr 2019;6:423.

Cunnion KM, Willis LK, Minto HB, et al. Eosinophil quantitated urine kinetic: a novel assay for assessment of eosinophilic esophagitis. Ann Allergy Asthma Immunol 2016;116:435-439.

Votto M, Marseglia GL, De Filippo M, et al. Early life risk factors in pediatric EoE: could we prevent this modern disease? Front Pediatr 2020;8:263.

O'Shea KM, Aceves SS, Dellon ES, et al. Pathophysiology of eosinophilic esophagitis. Gastroenterology 2018;154:333-345.

Ruffner MA, Cianferoni A. Phenotypes and endotypes in eosinophilic esophagitis. Ann Allergy Asthma Immunol 2020;124:233-239.

Blanchard C, Stucke EM, Burwinkel K, et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol 2010;184:4033-4041.

Aceves SS, Newbury RO, Chen D, et al. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy 2010;65:109-116.

Kitajima M, Lee HC, Nakayama T, et al. TSLP enhances the function of helper type 2 cells. Eur J Immunol 2011;41:1862-1871.

Hui CC, Rusta-Sallehy S, Asher I, et al. The effects of thymic stromal lymphopoietin and IL-3 on human eosinophil-basophil lineage commitment: relevance to atopic sensitization. Immun Inflamm Dis 2014;2:44-55.

Sleiman PM, Wang ML, Cianferoni A, et al. GWAS identifies four novel eosinophilic esophagitis loci. Nat Commun 2014;5:5593.

Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest 2006;116:536-547.

Wen T, Rothenberg ME. Clinical applications of the eosinophilic esophagitis diagnostic panel. Front Med (Lausanne) 2017;4:108.

Downloads

Published

29-11-2021

How to Cite

1.
Non-invasive biomarkers of eosinophilic esophagitis. Acta Biomed [Internet]. 2021 Nov. 29 [cited 2024 Jun. 12];92(S7):e2021530. Available from: https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/12401

Most read articles by the same author(s)

1 2 3 4 5 6 7 > >>