Image Analysis of Eosinophil Peroxidase Immunohistochemistry for Diagnosis of Eosinophilic Esophagitis.
Adolescent
Adult
Aged
Aged, 80 and over
Biopsy
Case-Control Studies
Eosinophil Peroxidase
/ analysis
Eosinophilic Esophagitis
/ diagnosis
Eosinophils
/ enzymology
Esophagus
/ pathology
Female
Humans
Image Processing, Computer-Assisted
/ methods
Immunohistochemistry
/ methods
Male
Middle Aged
Prospective Studies
Retrospective Studies
Staining and Labeling
/ methods
Young Adult
Biomarker
Degranulation
Eosinophil peroxidase
Eosinophilic esophagitis
Image analysis
Journal
Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
10
02
2020
accepted:
21
03
2020
pubmed:
6
4
2020
medline:
17
8
2021
entrez:
6
4
2020
Statut:
ppublish
Résumé
Diagnosis of eosinophilic esophagitis (EoE) requires manual quantification of tissue eosinophils. Eosinophil peroxidase (EPX) is an eosinophil-specific, cytoplasmic granule protein released during degranulation. The objective of this study was to evaluate image analysis of EPX immunohistochemistry as an automated method for histologic diagnosis of EoE. We performed a secondary analysis of prospectively collected esophageal biopsies obtained from adult subjects with EoE and controls. Tissue sections were stained with hematoxylin and eosin (H&E) and evaluated for peak eosinophils per high power field (eos/hpf). The same slides were de-stained and re-stained to detect EPX for direct comparison. Slides were digitized, and EPX staining area/mm Thirty-eight EoE cases and 49 controls were analyzed. Among EoE subjects, matched post-treatment biopsies were available for 21 responders and 10 non-responders. Baseline EPX/mm EPX/mm
Sections du résumé
BACKGROUND
Diagnosis of eosinophilic esophagitis (EoE) requires manual quantification of tissue eosinophils. Eosinophil peroxidase (EPX) is an eosinophil-specific, cytoplasmic granule protein released during degranulation.
AIMS
The objective of this study was to evaluate image analysis of EPX immunohistochemistry as an automated method for histologic diagnosis of EoE.
METHODS
We performed a secondary analysis of prospectively collected esophageal biopsies obtained from adult subjects with EoE and controls. Tissue sections were stained with hematoxylin and eosin (H&E) and evaluated for peak eosinophils per high power field (eos/hpf). The same slides were de-stained and re-stained to detect EPX for direct comparison. Slides were digitized, and EPX staining area/mm
RESULTS
Thirty-eight EoE cases and 49 controls were analyzed. Among EoE subjects, matched post-treatment biopsies were available for 21 responders and 10 non-responders. Baseline EPX/mm
CONCLUSIONS
EPX/mm
Identifiants
pubmed: 32248390
doi: 10.1007/s10620-020-06230-5
pii: 10.1007/s10620-020-06230-5
pmc: PMC7541435
mid: NIHMS1589002
doi:
Substances chimiques
Eosinophil Peroxidase
EC 1.11.1.-
Types de publication
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
775-783Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK090073
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034987
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101856
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK101856
Pays : United States
Organisme : Arizona Biomedical Research Commission
ID : ADHS18-198880
Références
Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology. 2018;155:1022–1033e1010.
doi: 10.1053/j.gastro.2018.07.009
Stucke EM, Clarridge KE, Collins MH, Henderson CJ, Martin LJ, Rothenberg ME. Value of an additional review for eosinophil quantification in esophageal biopsies. J Pediatr Gastroenterol Nutr. 2015;61:65–68.
doi: 10.1097/MPG.0000000000000740
Dellon ES, Aderoju A, Woosley JT, Sandler RS, Shaheen NJ. Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review. Am J Gastroenterol. 2007;102:2300–2313.
doi: 10.1111/j.1572-0241.2007.01396.x
Saffari H, Peterson KA, Fang JC, Teman C, Gleich GJ, Pease LF 3rd. Patchy eosinophil distributions in an esophagectomy specimen from a patient with eosinophilic esophagitis: implications for endoscopic biopsy. J Allergy Clin Immunol. 2012;130:798–800.
doi: 10.1016/j.jaci.2012.03.009
Nielsen JA, Lager DJ, Lewin M, Rendon G, Roberts CA. The optimal number of biopsy fragments to establish a morphologic diagnosis of eosinophilic esophagitis. Am J Gastroenterol. 2014;109:515–520.
doi: 10.1038/ajg.2013.463
Saffari H, Hoffman LH, Peterson KA, et al. Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2014;133:1728–1734e1721.
doi: 10.1016/j.jaci.2013.11.024
Peterson KA, Cobell WJ, Clayton FC, et al. Extracellular eosinophil granule protein deposition in ringed esophagus with sparse eosinophils. Dig Dis Sci. 2015;60:2646–2653. https://doi.org/10.1007/s10620-015-3665-1 .
doi: 10.1007/s10620-015-3665-1
pubmed: 25902747
Ochkur SI, Kim JD, Protheroe CA, et al. A sensitive high throughput ELISA for human eosinophil peroxidase: a specific assay to quantify eosinophil degranulation from patient-derived sources. J Immunol Methods. 2012;384:10–20.
doi: 10.1016/j.jim.2012.06.011
Protheroe C, Woodruff SA, de Petris G, et al. A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2009;7:749–755e711.
doi: 10.1016/j.cgh.2009.03.022
Martin LJ, Franciosi JP, Collins MH et al. Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease. J Allergy Clin Immunol. 2015;135:1519–1528e1518.
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.
Nguyen N, Baumgarten A, Wright BL, et al. Histologic similarities in children with eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. J Allergy Clin Immunol. 2019;143:1237–1240e1232.
Wright BL, Fernandez-Becker NQ, Kambham N, et al. Baseline gastrointestinal eosinophilia is common in oral immunotherapy subjects with IgE-mediated peanut allergy. Front Immunol. 2018;9:2624.
doi: 10.3389/fimmu.2018.02624
Lal D, Wright BL, Shim KP et al. Eosinophil peroxidase, GATA3, and T-bet as tissue biomarkers in chronic rhinosinusitis J Allergy Clin Immunol. 2019;143:2284–2287 e2286.
Wen T, Dellon ES, Moawad FJ, Furuta GT, Aceves SS, Rothenberg ME. Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation. J Allergy Clin Immunol. 2015;135:187–197.
doi: 10.1016/j.jaci.2014.08.043
Dellon ES, Rusin S, Gebhart JH, et al. Utility of a non-invasive serum biomarker panel for diagnosis and monitoring of EoE: a prospective study. Am J Gastroenterol. 2015;110:821–827.
doi: 10.1038/ajg.2015.57
Dellon ES, Cotton CC, Gebhart JH, et al. Accuracy of the eosinophilic esophagitis endoscopic reference score in diagnosis and determining response to treatment. Clin Gastroenterol Hepatol. 2016;14:31–39.
doi: 10.1016/j.cgh.2015.08.040
Eluri S, Selitsky SR, Perjar I, et al. Clinical and molecular factors associated with histologic response to topical steroid treatment in patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2019;17:1081–1088e1082.
doi: 10.1016/j.cgh.2018.09.005
Liacouras CA, Furuta GT, Hirano I et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults J Allergy Clin Immunol. 2011;128:3–20 e26; quiz 21–22.
Wolf WA, Cotton CC, Green DJ, et al. Evaluation of histologic cutpoints for treatment response in eosinophilic esophagitis. J Gastroenterol Hepatol Res. 2015;4:1780–1787.
doi: 10.17554/j.issn.2224-3992.2015.04.562
Reed CC, Wolf WA, Cotton CC, et al. Optimal histologic cutpoints for treatment response in patients with eosinophilic esophagitis: analysis of data from a prospective cohort study. Clin Gastroenterol Hepatol. 2017;16:226–233.
doi: 10.1016/j.cgh.2017.09.046
Dellon ES, Fritchie KJ, Rubinas TC, Woosley JT, Shaheen NJ. Inter- and intraobserver reliability and validation of a new method for determination of eosinophil counts in patients with esophageal eosinophilia. Dig Dis Sci.. 2010;55:1940–1949. https://doi.org/10.1007/s10620-009-1005-z .
doi: 10.1007/s10620-009-1005-z
pubmed: 19830560
Rusin S, Covey S, Perjar I, et al. Determination of esophageal eosinophil counts and other histologic features of eosinophilic esophagitis by pathology trainees is highly accurate. Hum Pathol. 2017;62:50–55.
doi: 10.1016/j.humpath.2016.12.017
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.
doi: 10.1093/dote/doz055
Kephart GM, Alexander JA, Arora AS, et al. Marked deposition of eosinophil-derived neurotoxin in adult patients with eosinophilic esophagitis. Am J Gastroenterol. 2010;105:298–307.
doi: 10.1038/ajg.2009.584
Schoepfer AM, Simko A, Bussmann C, et al. Eosinophilic esophagitis: relationship of subepithelial eosinophilic inflammation with epithelial histology. Endoscopy, blood eosinophils, and symptoms. Am J Gastroenterol. 2018;113:348–357.
doi: 10.1038/ajg.2017.493
Tottrup A, Fredens K, Funch-Jensen P, Aggestrup S, Dahl R. Eosinophil infiltration in primary esophageal achalasia. A possible pathogenic role. Dig Dis Sci. 1989;34:1894–1899. https://doi.org/10.1007/BF01536708 .
doi: 10.1007/BF01536708
pubmed: 2689111
Sridhara S, Ravi K, Smyrk TC, et al. Increased numbers of eosinophils, rather than only etiology, predict histologic changes in patients with esophageal eosinophilia. Clin Gastroenterol Hepatol. 2012;10:735–741.
doi: 10.1016/j.cgh.2012.01.008
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.
doi: 10.1016/j.cgh.2014.06.019
Dellon ES, Chen X, Miller CR, Woosley JT, Shaheen NJ. Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. Am J Gastroenterol. 2012;107:1503–1511.
doi: 10.1038/ajg.2012.202
Mueller S, Aigner T, Neureiter D, Stolte M. Eosinophil infiltration and degranulation in oesophageal mucosa from adult patients with eosinophilic oesophagitis: a retrospective and comparative study on pathological biopsy. J Clin Pathol. 2006;59:1175–1180.
doi: 10.1136/jcp.2005.031922
Strasser DS, Seger S, Bussmann C, et al. Eosinophilic oesophagitis: relevance of mast cell infiltration. Histopathology. 2018;73:454–463.
doi: 10.1111/his.13653
Sur S, Glitz DG, Kita H, et al. Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes. J Leukoc Biol.. 1998;63:715–722.
doi: 10.1002/jlb.63.6.715
Collins MH, Martin LJ, Alexander ES, et al. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus. 2017;30:1–8.
pubmed: 26857345
Whelan KA, Godwin BC, Wilkins B, et al. Persistent basal cell hyperplasia is associated with clinical and endoscopic findings in patients with histologically inactive eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2019. https://doi.org/10.1016/j.cgh.2019.08.055 .
doi: 10.1016/j.cgh.2019.08.055
pubmed: 31499251
Warners MJ, Ambarus CA, Bredenoord AJ, et al. Reliability of histologic assessment in patients with eosinophilic oesophagitis. Aliment Pharmacol Ther. 2018;47:940–950.
doi: 10.1111/apt.14559
Hirano I, Collins MH, Assouline-Dayan Y, et al. A randomized, double-blind, placebo-controlled trial of a novel recombinant, humanized, anti-interleukin-13 monoclonal antibody (RPC4046) in patients with active eosinophilic esophagitis: results of the HEROES study. United Eur Gastroenterol J. 2016;4:OP325.
Schoepfer AM, Straumann A, Panczak R, et al. Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis. Gastroenterology. 2014;147:1255–1266e1221.
doi: 10.1053/j.gastro.2014.08.028
Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut. 2013;62:489–495.
doi: 10.1136/gutjnl-2011-301817
Lin Z, Kahrilas PJ, Xiao Y, et al. Functional luminal imaging probe topography: an improved method for characterizing esophageal distensibility in eosinophilic esophagitis. Therap Adv Gastroenterol. 2013;6:97–107.
doi: 10.1177/1756283X12470017