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. 2024 Aug 29;37(9):doae034.
doi: 10.1093/dote/doae034.

Expression of inducible nitric oxide synthase, nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3 in patients with gastroesophageal reflux disease, eosinophilic esophagitis, and in healthy controls: a semiquantitative image analysis of 3,3'-diaminobenzidine-stained esophageal biopsies

John Plate  1   2 , Mogens Bove  1   2 , Helen M Larsson  1   2 , Elisabeth Norder Grusell  3 , Nabanita Chatterjee  4 , Leif E Johansson  5 , Henrik Bergquist  2
Affiliations

Expression of inducible nitric oxide synthase, nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3 in patients with gastroesophageal reflux disease, eosinophilic esophagitis, and in healthy controls: a semiquantitative image analysis of 3,3'-diaminobenzidine-stained esophageal biopsies

John Plate et al. Dis Esophagus. .

Abstract

Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share many histopathological features; therefore, markers for differentiation are of diagnostic interest and may add to the understanding of the underlying mechanisms. The nitrergic system is upregulated in GERD and probably also in EoE. Esophageal biopsies of patients with EoE (n = 20), GERD (n = 20), and healthy volunteers (HVs) (n = 15) were exposed to antibodies against inducible nitric oxide synthase (iNOS), nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3. The stained object glasses were randomized, digitized, and blindly analyzed regarding the expression of DAB (3,3'-diaminobenzidine) by a protocol developed in QuPath software. A statistically significant overexpression of iNOS was observed in patients with any of the two inflammatory diseases compared with that in HVs. Eotaxin-3 could differentiate HVs versus inflammatory states. Gastroesophageal reflux patients displayed the highest levels of nitrotyrosine. Neither iNOS nor nitrotyrosine alone were able to differentiate between the two diseases. For that purpose, eosinophil peroxidase was a better candidate, as the mean levels increased stepwise from HVs via GERD to EoE. iNOS and nitrotyrosine are significantly overexpressed in patients with EoE and GERD compared with healthy controls, but only eosinophil peroxidase could differentiate the two types of esophagitis. The implications of the finding of the highest levels of nitrotyrosine among gastroesophageal reflux patients are discussed.

Keywords: eosinophilic esophagitis; gastroesophageal reflux disease; image analysis; immunohistochemistry.

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Figures

Graphical Abstract
Graphical Abstract
Fig. 1
Fig. 1
EoE patient. Antibody: eosinophilic peroxydase (EPX). The two most affected ROIs marked before (a) and after (b) positive cell detection.
Fig. 2
Fig. 2
GERD patient. Antibody: inducible nitric oxide synthase (iNOS). Brownish DAB-stain of basal layers and adjoining submucosa. Distinct DIS (mainly in middle layers).
See this image and copyright information in PMC

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