Lower esophageal sphincter muscle of patients with achalasia exhibits profound mast cell degranulation

Melissa Nelson, Xi Zhang, Robert M Genta, Kevin Turner, Eitan Podgaetz, Shere Paris, Jacob Cardenas, Jinghua Gu, Steven Leeds, Marc Ward, Anh D Nguyen, Vani Konda, Glenn T. Furuta, Zui Pan, Rhonda F. Souza, Stuart Jon Spechler

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Eosinophils and mast cells are key effectors of allergy. When they accumulate in the esophagus, their myoactive, pro-inflammatory, and cytotoxic products potentially could cause achalasia-like motility abnormalities and neuronal degeneration. We hypothesized that there is an allergy-mediated form of achalasia. Methods: LES muscle samples obtained during Heller myotomy from patients with achalasia or EGJ outflow obstruction (EGJOO) and from organ donor controls were immunostained for tryptase. Eosinophil and mast cell density, and mast cell degranulation were assessed. LES muscle was evaluated by qPCR for genes mediating smooth muscle Ca2+ handling and contraction. Key Results: There were 13 patients (7 men, median age 59; 10 achalasia, 3 EGJOO) and 7 controls (4 men, median age 42). Eosinophils were infrequent in LES muscle, but mast cells were plentiful. Patients and controls did not differ significantly in LES mast cell density. However, 12 of 13 patients exhibited profound LES mast cell degranulation involving perimysium and myenteric plexus nerves, while only mild degranulation was seen in 2 of 7 controls. Hierarchical clustering analysis of qPCR data revealed two “mototype” LES gene expression patterns, with all type II patients in one mototype, and type I and III patients in the other. Conclusions & Inferences: LES muscle of patients with achalasia or EGJOO exhibits striking mast cell degranulation, and patients with different achalasia manometric phenotypes exhibit different LES patterns of expression for genes mediating Ca2+ handling and muscle contraction. Although these findings are not definitive, they support our hypothesis that achalasia can be allergy-driven.

Original languageEnglish (US)
JournalNeurogastroenterology and Motility
DOIs
StateAccepted/In press - 2020
Externally publishedYes

Keywords

  • allergy
  • eosinophilic esophagitis
  • esophageal motility disorder
  • gene expression
  • smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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