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Review
. 2023 Dec;152(6):1382-1393.
doi: 10.1016/j.jaci.2023.08.021. Epub 2023 Sep 3.

Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma & Immunology Meeting

Mirna Chehade  1 , Benjamin L Wright  2 , Dan Atkins  3 , Seema S Aceves  4 , Steven J Ackerman  5 , Amal H Assa'ad  6 , Maureen Bauer  3 , Margaret H Collins  6 , Scott P Commins  7 , Carla M Davis  8 , Evan S Dellon  9 , Bethan Doerfler  10 , Gerald J Gleich  11 , Sandeep K Gupta  12 , David A Hill  13 , Elizabeth T Jensen  14 , David Katzka  15 , Kara Kliewer  6 , Ellyn Kodroff  16 , Leah C Kottyan  17 , Shay Kyle  16 , Amanda B Muir  13 , Robert D Pesek  18 , Kathryn Peterson  19 , Wayne G Shreffler  20 , Jonathan M Spergel  13 , Mary Jo Strobel  21 , Joshua Wechsler  22 , Nives Zimmermann  6 , Glenn T Furuta  3 , Marc E Rothenberg  6
Affiliations
Review

Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma & Immunology Meeting

Mirna Chehade et al. J Allergy Clin Immunol. 2023 Dec.

Abstract

The Consortium of Eosinophilic Gastrointestinal Diseases and The International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured a review of recent discoveries in the basic biology and pathogenesis of eosinophilic gastrointestinal diseases (EGIDs) in addition to advances in our understanding of the clinical features of EGIDs. Diagnostic and management approaches were reviewed and debated, and clinical trials of emerging therapies were highlighted. Herein, we briefly summarize the breakthrough discoveries in EGIDs.

Keywords: Eosinophilic esophagitis; eosinophil; eosinophilic gastritis; food allergy.

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Conflict of interest statement

MC is a consultant for Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Nexstone Immunology, Allakos, Shire/Takeda, and Phathom, and received research funding from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone, and Bristol Myers Squibb; CMD has received research funding from the National Institutes of Health/National Institute of Allergy and Infectious Disease (Consortium of Food Allergy Research/Consortium of Eosinophilic Gastrointestinal Researchers), DBV Technologies, Aimmune Therapeutics, Regeneron Pharmaceuticals, and Allergenis; ETJ has consulted for Regeneron Pharmaceuticals, Jazz Pharmaceuticals, and TARGET-RWE; MB received consulting fees from Sanofi; NZ served as scientific advisory member at Blueprint Medicines; SPC has received fees from Genentech (advisory), Up-To-Date (honoraria), and Revivicor (research grant); SSA received consultant fees for Regeneron, AstraZeneca, Bristol Meyers Squibb, research funding from Implicit Biosciences, is co-inventor of oral viscous budesonide UCSD patent Takeda license, and received educational speaker fees from Sanofi/Genzyme, and Regeneron; SJA is the CSO and co-founder of EnteroTrack, LLC., the company marketing the Esophageal String Test for use in patients with EoE; ABM received research funding from Morphic, and served on the medical advisory board for Bristol Myers Squib and Nexstone Immunology; DAK received compensation for research with Medtronic and consultant fees from Sanofi; ESD received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda, has received consultant fees from Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio, and received educational grants from Allakos, Holoclara, and Invea; GF serves as CMO for EnteroTrack and received research funding from Arena/Pfizer, Holoclara, and NIH; JMS received grant support from Regeneron/Sanofi, Novartis, NIH, FARE, is a consultant for Regeneron, Sanofi, Alladapt, Readysetfood, and ARS Pharmacy, and received royalties from Uptodate; JBW is a consultant for Allakos, Ellodi, Regeneron, Sanofi/Genzyme, AstraZeneca, and Invea Therapeutics, and received clinical trial/research funding from Allakos, Invea Therapeutics and Sanofi-Regeneron; KP is a consultant or advisory member for AGA, Alladapt, AstraZeneca, Allakos, Bristol Meyers Squibb, Ellodi, Invea, Lucid, Nexstone, WebMD, Peerview, Regeneron, Takeda, and WebMD, has received research funding from AstraZeneca, Allakos, Adare, Regeneron-Sanofi, Revolo, Celldex, and Ellodi, received speaker fees from AGA, Regeneron, Peerview, Takeda, Allakos, and WebMD, received grant support (unrestricted) from Allakos and Chobani, and has equity in Nexeos Bio; MER is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, Santa Ana Bio, Bristol Myers Squibb, Astra Zeneca, Pfizer, GlaxoSmith Kline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first eight listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate, and is an inventor of patents owned by Cincinnati Children’s Hospital; MHC is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc./Alimentiv, Inc. and Shire, a Takeda company; RDP is a consultant for Regeneron, Inc.; SKD has been a consultant, DSMB member, or author for Adare, BMS, QOL, Takeda, MedScape, PVI, GI ReConnect, and UpToDate; WGS received clinical trial funding from Aimmune, ALK, Celgene, DBV, Genentech, Novartis, Regeneron, and Vedanta, served on scientific advisory boards for Aimmune and FARE, received personal consulting fees from Aimmune/Nestle, Harmony, Merk, and Novartis, received royalties from UpToDate, and received grants from NIH, Demarest Lloyd Foundation, Thornhill Foundation, Food Allergy Science Initiative; AHA, BD, DAH, GJG, KK, LCK, MJS, BLW, EK, DA, and SK have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Model of EoE pathophysiology. Allergen penetration resulting from impaired barrier function (IBF) induces the production of thymic stromal lymphopoietin (TSLP) and interleukin-33 (IL-33) by esophageal epithelial cells leading to the production of IL-4 that promotes T helper 2 cell (Th2) differentiation resulting in further release of IL-4 which, in combination with IL-13 induced by Th2 cells, promotes the release of eotaxin-3, a powerful eosinophil chemoattractant. IL-5, generated by Th2 cells, mast cells, and eosinophils, also impacts recruited eosinophils, and together these activated cells produce transforming growth factor beta (TGFβ1) that stimulates fibroblast activation and epithelial-mesenchymal transition which leads to increased subepithelial extracellular matrix deposition. In addition, IL-13 disrupts epithelial integrity by increasing the production of Calpain 14, downregulating desmoglein-1, and causing dysregulation of the epidermal differentiation complex leading to IBF. Recently, IL-13 has been shown to induce loss of tetraspanin 12 (TSPAN 12) in endothelial cells resulting in endothelial dysfunction and changes in gene expression impacting esophageal remodeling.
Figure 2.
Figure 2.
Multidisciplinary Team for EGID. A multidisciplinary team for a patient with EGID often consists of gastroenterologists, allergists/immunologists, pathologists, and dieticians, along with many other potential specialists. A wide range of physicians, health workers, and their primary care provider can play a role to support the quality of life and medical care of a patient with EGID.
Figure 3.
Figure 3.
Empiric Elimination Diets for EoE. The efficacy of the empiric 6-food elimination diet (milk, egg, wheat, soy, peanut/tree nuts, fish/shellfish) approaches 70%. Variations of empiric elimination diets have been used moving from the least to the most restrictive diet (step up) or vice versa (step down). Efficacy ranges from about 44% for the 2-food elimination diet to 60% for the 4-food elimination diet.
See this image and copyright information in PMC

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