Mast cell‐pain connection in eosinophilic esophagitis

Zhang, Simin; Shoda, Tetsuo; Aceves, Seema S.; Arva, Nicoleta C.; Chehade, Mirna; Collins, Margaret H.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Khoury, Paneez; Leung, John; Spergel, Amanda K. Rudman; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang–Yu; Furuta, Glenn T.; Rothenberg, Marc E.

doi:10.1111/all.15260

Cited by 21 publications

(7 citation statements)

References 7 publications

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“…Of note, mast cells remain activated even during disease remission [ 70 ]. They might contribute to ongoing symptoms and particularly pain, in otherwise well-controlled disease [ 71 , 72 ], although this finding has been inconsistent. Expression of TRPV1 (pain-associated gene) and co-expression of CPA3 and HPGDS (as surrogate markers for mast cells) correlated in active and inactive EoE and were significantly increased in patients with pain regardless of EoE activity, while there was no such relation with eosinophilia [ 72 ].…”

Section: Eoe Beyond Eosinophilsmentioning

confidence: 99%

Eosinophilic Esophagitis beyond Eosinophils – an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023

Nunes¹,

Straumann²,

Nunes³

et al. 2023

Int Arch Allergy Immunol

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Having long been considered the mainstay in eosinophilic esophagitis (EoE) diagnosis and pathogenesis, the role of eosinophils has been questioned and might be less important than previously thought. It is well known now that EoE is a Th2-mediated disease with many more disease features than eosinophilic infiltration. With more knowledge on EoE, less pronounced phenotypes or nuances of the disease have become apparent. In fact, EoE might be only the tip of the iceberg (and the most extreme phenotype) with several variant forms, at least three, lying on a disease spectrum. Although a common (food induced) pathogenesis has yet to be confirmed, gastroenterologists and allergologists should be aware of these new phenomena in order to further characterize these patients. In the following review, we discuss the pathogenesis of EoE, particularly those mechanisms beyond eosinophilic infiltration of the esophageal mucosa, non-eosinophilic inflammatory cell populations, the new disease entity EoE-like disease, variant forms of EoE, and the recently coined term mast cell esophagitis.

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Section: Eoe Beyond Eosinophilsmentioning

confidence: 99%

Eosinophilic Esophagitis beyond Eosinophils – an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023

Nunes¹,

Straumann²,

Nunes³

et al. 2023

Int Arch Allergy Immunol

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“…Martin et al [40] found a correlation between mast cell gene levels and counts with dysphagia scores in children measured by the Pediatric Eosinophilic Esophagitis Symptom Score 2.0 in children that was superior to eosinophils. Zhang et al found increased levels of two mast cell genes: Carboxypeptidase A3 ( CPA3 ) and Hematopoietic Prostaglandin D Synthase among children and adults with EoE who have chest pain; however, did not see a relationship with dysphagia [34 ▪ ]. Interestingly, this gene combination correlated with Transient Receptor Potential Cation Channel Subfamily V Member 1 ( TRPV1 ) gene levels, a nerve pain receptor, and found mast cells nearby TRPV1+ neurons.…”

Section: Mast Cell Hyperplasia As a Biomarker In Eosinophilic Esophag...mentioning

confidence: 99%

“…Mast cells are tissue resident granulocytes that are increased in EoE in density and activation [11,27 ▪▪ ,28–33] yet are largely ignored because of the necessity for special stains to identify their presence. Mast cells have been implicated in a variety of pathogenic functions in EoE [17 ▪▪ ,27 ▪▪ ,29,32,34 ▪ ,35–40]. This review will present what is known from recent research on the involvement of mast cells in EoE, and identify questions requiring further investigation…”

Section: Introductionmentioning

confidence: 99%

Role of mast cells in eosinophilic esophagitis

Janarthanam

Bolton

Wechsler

2022

Current Opinion in Gastroenterology

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Purpose of reviewThis review will present what is known from recent research on the involvement of mast cells in eosinophilic esophagitis and identify questions requiring further investigation.Recent findingsIn the adults and children with eosinophilic esophagitis, there is increasing evidence that mastocytosis can persist, despite resolution of eosinophilia and is associated with persistent mucosal abnormalities and symptoms. Despite, treatment mast cells have an activated transcriptome. Mast cells likely contribute to epithelial barrier dysfunction, smooth muscle hypertrophy and contraction, and subepithelial fibrosis. It remains unclear whether targeting MCs alone has therapeutic efficacy to improve tissue damage.SummaryMast cells appear to play a key role in eosinophilic esophagitis and serve as a biomarker of mucosal healing in conjunction with eosinophils. Excessive mast cell activation likely contributes to tissue damage in eosinophilic esophagitis and need to be considered as a target of therapy along with eosinophils.

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“…Notably, there is concurrent mastocytosis and some evidence of mast cell degranulation in the esophageal epithelium [6][7][8] . Furthermore, the density of mast cells correlates more highly with certain symptoms and histologic features than eosinophils, suggesting that mast cells are clinically relevant and involved in disease pathogenesis, including esophageal epithelial barrier disruption [9][10][11][12][13] . Unlike eosinophils, which do not reside in the esophageal epithelium in healthy states, mast cells exist in small numbers in the esophageal epithelium and in the esophageal lamina propria (LP) during homeostasis 8 .…”

Section: Introductionmentioning

confidence: 99%

Machine Learning Based Identification and Characterization of Mast cells in Eosinophilic Esophagitis

Zhang,

Caldwell,

Rochman

et al. 2023

Preprint

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BackgroundEosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis.ObjectiveUsing machine learning, we localized and characterized esophageal mast cells to decipher their potential role in disease pathology.MethodsEsophageal biopsy samples (EoE, control) were stained for mast cells by anti-tryptase and imaged using immunofluorescence; high-resolution whole tissue images were digitally assembled. Machine learning software was trained to identify, enumerate, and characterize mast cells, designated Mast Cell-Artificial Intelligence (MC-AI).ResultsMC-AI enumerated cell counts with high accuracy. During active EoE, epithelial mast cells increased and lamina propria (LP) mast cells decreased. In controls and EoE remission patients, papillae had the highest mast cell density and negatively correlated with epithelial mast cell density. Mast cell density in the epithelium and papillae correlated with the degree of epithelial eosinophilic inflammation, basal zone hyperplasia, and LP fibrosis. MC-AI detected greater mast cell degranulation in the epithelium, papillae, and LP in EoE patients compared with control individuals. Mast cells were localized further from the basement membrane in active EoE than EoE remission and controls individuals but were closer than eosinophils to the basement membrane in active EoE.ConclusionUsing MC-AI, we identified a distinct population of homeostatic esophageal papillae mast cells; during active EoE, this population decreases, undergoes degranulation, negatively correlates with epithelial mast cell levels, and significantly correlates with distinct histologic features. Overall, MC-AI provides a means to understand the potential involvement of mast cells in EoE and other disorders.Clinical ImplicationWe have developed a methodology for identifying, enumerating, and characterizing mast cells using artificial intelligence; this has been applied to decipher eosinophilic esophagitis and provides a platform approach for other diseases.Capsule SummaryA machine learning protocol for identifying mast cells, designated Mast Cell–Artificial Intelligence, readily identified spatially distinct and dynamic populations of mast cells in EoE, providing a platform to better understand this cell type in EoE and other diseases.

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Mast cell‐pain connection in eosinophilic esophagitis

Cited by 21 publications

References 7 publications

Eosinophilic Esophagitis beyond Eosinophils – an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023

Eosinophilic Esophagitis beyond Eosinophils – an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023

Role of mast cells in eosinophilic esophagitis

Machine Learning Based Identification and Characterization of Mast cells in Eosinophilic Esophagitis

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