University of Oulu

Zand Irani, M., Talley, N. J., Ronkainen, J., Aro, P., Andreasson, A., Agreus, L., Vieth, M., Jones, M. P., & Walker, M. M. (2021). Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms. Human Pathology, 115, 112–122.

Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms

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Author: Irani, Mudar Zand1,2; Talley, Nicholas J.1,2,3; Ronkainen, Jukka4,5;
Organizations: 1University of Newcastle, Newcastle, Australia
2Hunter Medical Research Institute, New Lambton Heights, Australia
3NHMRC Centre of Research Excellence in Digestive Health
4Center for Life Course Health Research, University of Oulu, Finland
5Primary Health Care Centre, Tornio, Finland
6Arokero OY, Tornio, Finland
7Department of Psychology, Macquarie University, North Ryde, Australia
8Stress Research Institute, Department of Psychology, Stockholm University, Stockholm, Sweden
9Department of Medicine Solna, Karolinska Institutet, Sweden
10Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
11Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2022-06-25


Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32–37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13–2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.

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Series: Human pathology
ISSN: 0046-8177
ISSN-E: 1532-8392
ISSN-L: 0046-8177
Volume: 115
Pages: 112 - 122
DOI: 10.1016/j.humpath.2021.06.004
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: Supported in part by the Swedish Research Council; the Swedish. Society of Medicine; Mag-tarm sjukas förbund, Norrbotten County. Council, Sweden; AstraZeneca R&D, Sweden.
Copyright information: © 2021 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license