Allergologia et Immunopathologia

Allergologia et Immunopathologia

Volume 47, Issue 5, September–October 2019, Pages 431-436
Allergologia et Immunopathologia

Original Article
Increased number of regulatory T cells in esophageal tissue of patients with eosinophilic esophagitis in comparison to gastro esophageal reflux disease and control groups

https://doi.org/10.1016/j.aller.2019.02.005Get rights and content

Abstract

Background

Eosinophilic esophagitis (EoE) is a primarily polygenic allergic disorder. Although most patients have IgE sensitization, it seems that non-IgE mediated responses mainly contribute to the pathogenesis of EoE. Regulatory T cells (Tregs) may have an important role in allergies. There are limited data on the association of Tregs and EoE. In this study, we enumerated and compared T lymphocytes and Tregs in esophageal tissue of patients with EoE, gastroesophageal reflux disease (GERD) and normal controls.

Methods

Ten patients with EoE, ten patients with GERD and eight normal controls were included. Immunohistochemistry staining was used to enumerate T lymphocytes and Tregs. CD3+ cells were considered as T cells and FOXP3+, CD3+ cells were considered as Tregs. T cells and Tregs were counted in 10 high power fields (HPF) (×400) for each patient and the average of 10 HPFs was recorded.

Results

The mean ± SEM of Tregs in esophageal tissue of patients with EoE (10.90 ± 2.14 cells/HPF) was significantly higher than the GERD (2.77 ± 0.66 cells/HPF) and control groups (0.37 ± 0.08 cells/HPF) (P < 0.001). Additionally, the mean ± SEM of T lymphocytes in esophageal tissue of patients with EoE (24.39 ± 3.86 cells/HPF) were increased in comparison to the GERD (10.07 ± 2.65 cells/HPF) and control groups (3.17 ± 0.93 cells/HPF) (P < 0.001).

Conclusion

There is an increase in the number of esophageal T lymphocytes and regulatory T cells in patients with EoE compared to the GERD and control groups.

Introduction

Eosinophilic esophagitis (EoE) is one of the eosinophilic gastrointestinal disorders that involve both IgE-mediated and delayed Th2 responses. The normal esophagus tissue does not contain any eosinophils, and finding eosinophils in esophageal epithelium indicates a pathologic disorder.1, 2, 3 Patients typically suffer from vomiting, epigastric or chest pain, dysphagia, and food impactions.4 Symptoms are similar to those of gastroesophageal reflux disease (GERD). Quantitation of eosinophils is helpful to distinguish EoE from GERD. Up to seven eosinophils/HPF (×400) is most indicative of GERD, while more than 15 eosinophils/HPF is characteristic of EoE.5 There has been an increase in the prevalence and incidence of the disease in the last decade.6

Eosinophilic esophagitis is considered as a chronic antigen driven disease, in which food and/or aeroallergens induce an eosinophilic infiltration in the esophagus.7 Although most patients have IgE sensitization, it seems that non-IgE mediated responses mainly contribute to the pathogenesis of EoE.3 Most EoE patients have another allergic disease such as food sensitivity, eczema, allergic rhinitis and asthma.8, 9, 10 Some studies11, 12 suggest that regulatory T cells (Tregs) that express the forkhead box P3 (FoxP3) gene are crucial in protecting against allergic diseases and maintaining self-tolerance. Reduction in the frequency or function of Tregs has been reported to be associated with allergies and eosinophilia.11, 12, 13, 14 It has also been found that total thymic Foxp3 mRNA expression is increased in non-atopic children, whereas Treg cell maturation is significantly delayed in atopic children.15 There are limited data on the association of Tregs and EoE.6, 16, 17, 18

This study was designed to enumerate Tregs in esophageal tissue of pediatric patients with EoE in comparison to patients with GERD and normal controls.

Section snippets

Materials and methods

This prospective study was performed on pediatric patients of Mofid Children's Hospital, Tehran, Iran. Ten patients with EoE, ten patients with GERD and eight normal controls were included. The EoE group consisted of patients with at least 15 eosinophils/HPF in evaluation of H&E slides of esophagus biopsy, normal PH in esophagus and were not responsive to anti-reflux therapy (pantoprazole or esomeprazole) for four to eight weeks. The GERD group had fewer than 15 eosinophils/HPF in esophageal

Results

A total of 28 children were studied. There was no significant difference between the ages of the three groups (P = 0.86) (Table 1). The characteristics of the patient in all three groups are summarized in Table 2.

Regulatory T cells and T lymphocytes were counted on epithelium layer of esophagus tissue (Fig. 1). The mean ± SEM of Tregs in esophageal tissue of patients with EoE (10.90 ± 2.14 cells/HPF) was significantly higher than the GERD (2.77 ± 0.66 cells/HPF) and control groups (0.37 ± 0.08 cells/HPF) (P <

Discussion

Eosinophilic esophagitis is a chronic eosinophilic inflammatory disease of the esophagus. Although most patients have IgE sensitization, it seems that non-IgE mediated responses have a more important role in pathogenesis of EoE.3, 10

There is a strong relation between EoE and atopy.10, 19, 20, 21 In this study almost all the patients had a concomitant allergic disorder along with EoE, such as food allergy, allergic rhinitis and urticaria (Table 2). Atopic sensitization commonly occurs early in

Statement of ethics

The study was ethically approved by the ethical committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran (approval number: IR.SBMU.RAM.REC.1394.118). All parents signed an informed consent.

Funding source

This research was funded by a grant (No. 5869), provided by Pediatric Pathology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Authors’ contribution

Fatemeh Mousavinasab: design of the work, acquisition, analysis, and interpretation of data, drafting and revising the manuscript.

Delara Babaie: design of the work, acquisition, analysis, and interpretation of data, revising the manuscript.

Yalda Nilipour: design of the work, acquisition of data.

Mahboubeh Mansouri: design of the work, acquisition of and interpretation of data.

Farid Imanzadeh: acquisition and interpretation of data.

Naghi Dara: acquisition and interpretation of data.

Pejman Rohani:

Conflict of interest

The authors have no conflict of interest to declare.

Acknowledgement

The authors wish to thank Ms. Zaynab Nasehi for her technical assistance.

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