Association of mast cells with clinical, endoscopic, and histologic findings in adults with eosinophilic esophagitis

Tappata, Manaswita; Eluri, Swathi; Perjar, Irina; Hollyfield, Johnathan; Betancourt, Renée; Randall, Cara; Woosley, John T.; Wechsler, Joshua B.; Dellon, Evan S.

doi:10.1111/all.13530

Cited by 25 publications

(10 citation statements)

References 9 publications

(11 reference statements)

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“…Consistent with findings in EG tissue, as well as previously published findings, mast cells and eosinophils were significantly increased to a similar extent compared with nondiseased esophageal tissue ( Figure 1, E and F, and refs. [12][13][14][15][16]. These data demonstrate that both eosinophils and mast cells are markedly and proportionally elevated in both EG and EoE patient tissue and support our flow cytometry-based approach to quantitatively assess immune cells in fresh human tissue.…”

Section: Eg and Eoe Tissues From Patients Have Elevated Numbers Of Bosupporting

confidence: 72%

“…A role for mast cells driving EGID pathogenesis is supported by the association of EGIDs with atopic diseases, the effectiveness of dietary therapy, and induction of immediate-and late-phase allergic reactions upon mast cell activation via high-affinity IgE receptors (12,13,32). Earlier studies in EoE have shown that mast cells are elevated and correlate with clinical symptoms as well as endoscopic and histologic findings (14). To better define the role of mast cells and eosinophils in EG, we used flow cytometry to characterize fresh gastric tissue from EG and nondiseased subjects at the single-cell level and found that both eosinophils and mast cells were selectively and significantly increased in EG gastric tissue.…”

Section: Discussionmentioning

confidence: 99%

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Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis

et al. 2019

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Inc. BSB is a paid consultant on the scientific advisory board of Allakos, Inc., and owns stock in Allakos. He is a coinventor on an existing Siglec-8related patent (US20080213212A1) and thus may be entitled to a share of royalties received by Johns Hopkins University on the potential sales of such products. He is also a cofounder of Allakos, which makes him subject to certain restrictions under university policy. The terms of this arrangement are being managed by the Johns Hopkins University and Northwestern University in accordance with their conflict of interest policies.

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Section: Eg and Eoe Tissues From Patients Have Elevated Numbers Of Bosupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis

et al. 2019

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“…This study was a secondary analysis of data and biospecimens collected during a prospective cohort study and was approved by the UNC IRB (#15-0163). Details of the parent study have been previously described [29][30][31][32][33], and subjects who participated provided informed consent for future use of banked biopsy samples. In brief, adults (age 18-80) who were undergoing a clinically indicated upper endoscopy for upper gastrointestinal (GI) symptoms (dysphagia, heartburn, chest pain or abdominal pain) were enrolled.…”

Section: Methodsmentioning

confidence: 99%

Lack of association of the esophageal microbiome in adults with eosinophilic esophagitis compared with non-EoE controls

Johnson

Dellon

McCoy

et al. 2021

JGLD

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Background and Aims: Changes in the esophageal microbiome have been reported in children with eosinophilic esophagitis (EoE), but few data exist for adults. We aimed to determine whether the esophageal microbiome differs in adults with and without EoE. Methods: In a prospective cohort study, adults undergoing outpatient endoscopy were enrolled as incident EoE cases or non-EoE controls. Clinical, endoscopic, and histologic data were collected. An esophageal biopsy was utilized for microbiome analysis. Bacterial DNA was extracted and the V3-V4 region of the 16S rRNA gene was amplified and sequenced. Analyses were performed comparing microbiome features for cases and controls, and within cases for disease features, with correction for multiple hypothesis testing. Results: A total of 24 incident EoE cases (mean age 40 years; 63% male; 100% white; 97 eos/hpf) and 25 controls (mean age 48, 36% male; 76% white; 1 eos/hpf) were analyzed. Principal coordinate analysis ordination failed to distinguish cases from controls. There were no microbiome differences within EoE cases based on clinical phenotype, presence of atopy, or endoscopic features. Use of proton pump inhibitors (PPIs), however, was significantly associated with 5 taxa including SR1 at the phylum level and Burkholderia at the genus level. Conclusions: There were no significant differences in the esophageal microbiome between newly diagnosed EoE cases and non-EoE controls in adults, or within EoE cases based on clinical features. However, given the strong rationale for the esophageal microbiome in EoE pathogenesis, future studies should explicitly consider the presence of PPIs as a confounding feature.

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“…11 Immunohistochemical staining of esophageal mucosal biopsies from EoE patients for mast cell tryptase regularly reveals increased numbers of intact and degranulated mast cells, often to the point that mast cell density (cells/mm 2 ) exceeds eosinophil density. 12,13 In addition, recent studies in children with EoE suggest that mast cells play an eosinophil-independent role in causing the clinical manifestations of the disease. 14 Like eosinophils, mast cells produce many pro-inflammatory cytokines and toxic molecules capable of damaging neurons.…”

Section: Introductionmentioning

confidence: 99%

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

Nelson

Zhang

Genta

et al. 2020

Neurogastroenterology Motil

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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 Ca 2+ 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 Ca 2+ handling and muscle contraction. Although these findings are not definitive, they support our hypothesis that achalasia can be allergy-driven.

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Association of mast cells with clinical, endoscopic, and histologic findings in adults with eosinophilic esophagitis

Abstract: To the Editor, Eosinophilic esophagitis (EoE) presents with diverse features which can differ between children and adults, as well as among adults, but eosinophils alone do not account for this heterogeneity. 1,2 Mast cells are involved in EoE pathogenesis, are highly increased

Cited by 25 publications

References 9 publications

Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis

Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis

Lack of association of the esophageal microbiome in adults with eosinophilic esophagitis compared with non-EoE controls

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

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