J Neurogastroenterol Motil  
Degranulated Eosinophils Contain More Fine Nerve Fibers in the Duodenal Mucosa of Patients With Functional Dyspepsia
Min Jin Lee,1 Hye-Kyung Jung,1* Ko Eun Lee,1 Yeung-Chul Mun,2 and Sanghui Park3
1Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea; 2Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea; and 3Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea
Correspondence to: Hye-Kyung Jung, MD, PhD
Department of Internal Medicine, School of Medicine, Ewha Womans University 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea
Tel: +82-2-2650-2874, Fax: +82-2-2650-2874, E-mail: junghk@ewha.ac.kr
Received: October 30, 2018; Revised: December 9, 2018; Accepted: January 8, 2019; Published online: February 18, 2019.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
Functional dyspepsia (FD) is characterized as chronic recurrent upper gastrointestinal symptoms in the absence of any organic disorder. We hypothesized that duodenal low-grade inflammation activates superficial afferent nerve sprouting, thereby contributing to hypersensitivity in patients with FD.
Methods
A prospective case-control study was conducted in a tertiary referral center. FD was defined using the Rome III criteria. Standardized endoscopic biopsies were performed in the stomach and duodenum. Hematoxylin and eosin staining and immunohistochemical staining for major basic proteins were performed to detect granulated eosinophil-derived granules, and S-100 staining was performed to detect fine nerve fibers.
Results
A total of 51 patients with FD (82% female; mean age 35.8 ± 13.4 years) and 35 controls were enrolled. Activated eosinophil counts in the duodenum were significantly higher in patients with FD than in controls (41.4% vs 17.1%, P = 0.005). Microscopic duodenitis was more frequently detected in patients with FD than in controls. Fine nerve fibers were more abundant in patients with FD than in controls (45.1% vs 11.4%, P = 0.029). The abundance of fine nerve fibers highly correlated with the degree of activated eosinophils.
Conclusions
Duodenal low-grade inflammation, such as mucosal eosinophilic accumulation with degranulation, promoted mucosal enteric nerve fiber density and sprouting in patients with FD.
Keywords: Duodenum; Dyspepsia; Eosinophils; Inflammation; Peripheral nervous system


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