Mast cell-pain connection in eosinophilic esophagitis

Simin Zhang¹, Tetsuo Shoda¹, Seema S Aceves^{2

3}, Nicoleta C Arva⁴, Mirna Chehade⁵, Margaret H Collins⁶, Evan S Dellon⁷, Gary W Falk⁸, Nirmala Gonsalves⁹, Sandeep K Gupta¹⁰, Ikuo Hirano⁹, Paneez Khoury¹¹, John Leung¹², Amanda K Rudman Spergel¹¹, Jonathan M Spergel¹³, Joshua B Wechsler¹⁴, Guang-Yu Yang¹⁵, Glenn T Furuta¹⁶, Marc E Rothenberg¹; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group

Affiliations

¹ Division of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
² Division of Allergy Immunology, Departments of Pediatrics and Medicine, University of California, San Diego, California, USA.
³ Rady Children's Hospital, San Diego, California, USA.
⁴ Department of Pathology, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
⁵ Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Division of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁷ Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
⁸ Division of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁹ Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁰ Division of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children/Indiana University School of Medicine, and Community Health Network, Indianapolis, Indiana, USA.
¹¹ National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
¹² Division of Gastroenterology, Tufts Medical Center, Boston, Massachusetts, USA.
¹³ Division of Allergy and Immunology, University of Pennsylvania Perelman School of Medicine/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹⁴ Division of Gastroenterology, Hepatology & Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
¹⁵ Department of Pathology, Northwestern University, Chicago, Illinois, USA.
¹⁶ Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA.

PMID: 35175645
PMCID: PMC9167217
DOI: 10.1111/all.15260

Mast cell-pain connection in eosinophilic esophagitis

Simin Zhang et al. Allergy. 2022 Jun.

. 2022 Jun;77(6):1895-1899.

doi: 10.1111/all.15260. Epub 2022 Mar 3.

Authors

Affiliations

¹ Division of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
² Division of Allergy Immunology, Departments of Pediatrics and Medicine, University of California, San Diego, California, USA.
³ Rady Children's Hospital, San Diego, California, USA.
⁴ Department of Pathology, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
⁵ Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Division of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁷ Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
⁸ Division of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁹ Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁰ Division of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children/Indiana University School of Medicine, and Community Health Network, Indianapolis, Indiana, USA.
¹¹ National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
¹² Division of Gastroenterology, Tufts Medical Center, Boston, Massachusetts, USA.
¹³ Division of Allergy and Immunology, University of Pennsylvania Perelman School of Medicine/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹⁴ Division of Gastroenterology, Hepatology & Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
¹⁵ Department of Pathology, Northwestern University, Chicago, Illinois, USA.
¹⁶ Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA.

PMID: 35175645
PMCID: PMC9167217
DOI: 10.1111/all.15260

No abstract available

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Conflict of interest statement

Conflicts of Interest

M.E.R. is a consultant for Pulm One, Spoon Guru, Allakos, ClostraBio, Serpin Pharm, Celgene, Shire, Astra Zeneca, GlaxoSmithKline, Allakos, Adare, Regeneron, and Novartis and has an equity interest in the first five, as well as royalties from reslizumab (Teva Pharmaceuticals) and Up-To-Date. M.E.R. is an inventor of patents owned by Cincinnati Children’s Hospital Medical Center. T.S. has funding from the NIH and is a co-inventor of patents owned by Cincinnati Children’s Hospital Medical Center. M.H.C. is a consultant for Alimentiv (formerly Robarts Clinical Trials, Inc), Allakos, Arena, AstraZeneca, Calypso, Esocap, GlaxoSmithKline, Receptos/Celgene/BMC, Regeneron, and Takeda and received research funds from Receptos/Celgene/BMC, Regeneron, and Takeda. J.B.W. is a consultant for Allakos, Regeneron, Sanofi/Genzyme, AstraZeneca, and InveniAI and received clinical trial support from Allakos and Regeneron. S.K.G. is a consultant Abbott, Adare, Allakos, Celgene, Gossamer Bio, QOL, UpToDate, Medscape, and Viaskin and received research support from Shire, Allakos, Adare, and CEGIR (NIH U54 AI117804). J.M.S. has funding from the NIH, Regeneron, Sanofi, Novartis, and FARE; is a consultant for Regeneron, Allakos, Sanofi, Novartis, and Takeda; and is an author for UptoDate. S.A.A. has funding from NIH and is an educational speaker for MedScape and Sanofi-Regeneron, a consultant for AstraZeneca, and an author for UpToDate. M.C. received consulting fees from Regeneron, Allakos, Adare/Ellodi, Shire/Takeda, AstraZeneca, Sanofi, and Bristol Myers Squibb and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, and Danone. E.S.D. received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, and Shire/Takeda; received consulting fees from Abbott, Abbvie, Adare/ Ellodi, Aimmune, Allakos, Amgen, Arena, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, GSK, Gossamer Bio, Landos, Morphic, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, and Shire/Takeda; and received educational grants from Allakos, Banner, and Holoclara. A.K.R.S.’s co-authorship of this publication does not necessarily constitute endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health or any other agency of the United States government. S.Z. has no relevant conflicts of interest. I.H. received research funding from Adare/Ellodi, Allakos, Arena, AstraZeneca, Meritage, Celgene/Receptos/BMS, Regeneron/Sanofi, and Shire/Takeda; received consulting fees from Adare/Ellodi, Allakos, Amgen, Arena, AstraZeneca, Celgene/Receptos/BMS, Eli Lilly, EsoCap, Gossamer Bio, Parexel/Calyx, Phathom, Regeneron, Sanofi, and Shire/Takeda; and is an educational speaker for MedScape and Sanofi-Regeneron.

Figures

**Figure 1.. MC and clinical feature association in EoE.**
A, Study methodology. B, MC count and MC-associated gene correlation (*CPA3*, left; *HPGDS*, middle; *CPA3+HPGDS* sum, right) (Spearman correlation). C, MC-low and MC-high comparison for disease parameters. *P < 0.05 and ****P < 0.0001 (Mann–Whitney U test). D, MC-low and MC-high comparison for two-way frequencies of pain (left) and dysphagia (right). *P < 0.05 (Chi-square test). CCHMC, Cincinnati Children’s Hospital Medical Center; CEGIR, Consortium of Eosinophilic Gastrointestinal Disease Researchers; MC, mast cell; EoE, eosinophilic esophagitis; EDP, EoE Diagnostic Panel; HSS, EoE Histology Scoring System; HPF, high-power field; NS, not significant.

**Figure 2.. MCs and TRPV1 associate with pain in EoE.**
**A-C,** *TRPV1* (A), *CPA3*+*HPGDS* sum (MCs surrogate marker) (B), and eosinophil parameters (C) in EoE by pain. *P < 0.05 and NS (Mann–Whitney U test). D, *TRPV1* correlates with MC-associated (*CPA3*+*HPGDS* sum) and eosinophil-associated genes (*CLC*) (Spearman correlation). E, Immunofluorescence staining of esophageal tissue for tryptase (green), TRPV1 (magenta), and DAPI (blue) (n=2). The MC (arrows)–nerve (arrowheads) distance is 45.70 μm (image 1) and 27.92 μm (image 2). MC, mast cell; EoE, eosinophilic esophagitis; HPF, high-power field; NS, not significant.

See this image and copyright information in PMC

References

1. Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018;155(4):1022–1033. - PMC - PubMed
1. Abonia JP, Blanchard C, Butz BB, et al. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol. 2010;126(1):140–149. - PMC - PubMed
1. Aguilera-Lizarraga J, Florens MV, Viola MF, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature. 2021;590(7844):151–156. - PMC - PubMed
1. Ma C, Schoepfer AM, Dellon ES, et al. Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS). J Allergy Clin Immunol. 2021. in press.
1. Hu Y, Liu Z, Yu X, Pasricha PJ, Undem BJ, Yu S. Increased acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol. 2014;307(2):G149–157. - PMC - PubMed

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Mast cell-pain connection in eosinophilic esophagitis

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Mast cell-pain connection in eosinophilic esophagitis

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