Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting

Benjamin L Wright¹, Juan Pablo Abonia², Edsel M Abud³, Seema S Aceves⁴, Steven J Ackerman⁵, Melinda Braskett⁶, Joy W Chang⁷, Mirna Chehade⁸, Gregory M Constantine⁹, Carla M Davis¹⁰, Evan S Dellon¹¹, Alfred D Doyle¹², Raquel Durban¹³, David A Hill¹⁴, Elizabeth T Jensen¹⁵, Anupama Kewalramani¹⁶, Paneez Khoury⁹, Amy D Klion⁹, Leah Kottyan², Fei Li Kuang¹⁷, Emily C McGowan¹⁸, Melanie A Ruffner¹⁴, Lisa A Spencer¹⁹, Jonathan M Spergel¹⁴, Amiko M Uchida²⁰, Joshua B Wechsler²¹, Robert D Pesek²²

Affiliations

¹ Department of Medicine, Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz; Division of Allergy and Immunology, Phoenix Children's Hospital, Phoenix, Ariz. Electronic address: wright.benjamin@mayo.edu.
² Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
³ Division of Allergy, Asthma, and Immunology, Scripps Clinic, San Diego, Calif; Division of Allergy and Immunology, University of California, San Diego, Rady Children's Hospital, San Diego, Calif.
⁴ Division of Allergy and Immunology, University of California, San Diego, Rady Children's Hospital, San Diego, Calif.
⁵ Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Ill.
⁶ Department of Pediatrics, Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Keck School of Medicine at University of Southern California, Los Angeles, Calif.
⁷ Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Mich.
⁸ Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY.
⁹ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
¹⁰ Department of Pediatrics, Division of Immunology, Allergy, and Retrovirology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.
¹¹ Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC.
¹² Department of Medicine, Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz.
¹³ Carolina Asthma and Allergy Center, Charlotte, NC.
¹⁴ Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pa.
¹⁵ Departments of Epidemiology and Prevention and Internal Medicine, Gastroenterology Section, Wake Forest University School of Medicine, Winston-Salem, NC.
¹⁶ Department of Pediatrics, Division of Pulmonology/Allergy, University of Maryland School of Medicine, Baltimore, Md.
¹⁷ Division of Allergy and Immunology, Northwestern Feinberg School of Medicine, Chicago, Ill.
¹⁸ Departments of Medicine and Pediatrics, Division of Allergy and Clinical Immunology, University of Virginia, Charlottesville, Va.
¹⁹ Department of Pediatrics, Section of Gastroenterology, Hepatology & Nutrition, University of Colorado School of Medicine, Aurora, Colo.
²⁰ Division of Gastroenterology, Hepatology & Nutrition, University of Utah, Salt Lake City, Utah.
²¹ Department of Pediatrics, Division of Gastroenterology, Hepatology & Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill.
²² Division of Allergy and Immunology, Arkansas Children's Hospital, and the University of Arkansas for Medical Sciences, Little Rock, Ark.

PMID: 39111348
PMCID: PMC11456379
DOI: 10.1016/j.jaci.2024.07.022

Review

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting

Benjamin L Wright et al. J Allergy Clin Immunol. 2024 Oct.

. 2024 Oct;154(4):882-892.

doi: 10.1016/j.jaci.2024.07.022. Epub 2024 Aug 5.

Authors

Affiliations

¹ Department of Medicine, Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz; Division of Allergy and Immunology, Phoenix Children's Hospital, Phoenix, Ariz. Electronic address: wright.benjamin@mayo.edu.
² Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
³ Division of Allergy, Asthma, and Immunology, Scripps Clinic, San Diego, Calif; Division of Allergy and Immunology, University of California, San Diego, Rady Children's Hospital, San Diego, Calif.
⁴ Division of Allergy and Immunology, University of California, San Diego, Rady Children's Hospital, San Diego, Calif.
⁵ Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Ill.
⁶ Department of Pediatrics, Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Keck School of Medicine at University of Southern California, Los Angeles, Calif.
⁷ Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Mich.
⁸ Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY.
⁹ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
¹⁰ Department of Pediatrics, Division of Immunology, Allergy, and Retrovirology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.
¹¹ Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC.
¹² Department of Medicine, Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz.
¹³ Carolina Asthma and Allergy Center, Charlotte, NC.
¹⁴ Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pa.
¹⁵ Departments of Epidemiology and Prevention and Internal Medicine, Gastroenterology Section, Wake Forest University School of Medicine, Winston-Salem, NC.
¹⁶ Department of Pediatrics, Division of Pulmonology/Allergy, University of Maryland School of Medicine, Baltimore, Md.
¹⁷ Division of Allergy and Immunology, Northwestern Feinberg School of Medicine, Chicago, Ill.
¹⁸ Departments of Medicine and Pediatrics, Division of Allergy and Clinical Immunology, University of Virginia, Charlottesville, Va.
¹⁹ Department of Pediatrics, Section of Gastroenterology, Hepatology & Nutrition, University of Colorado School of Medicine, Aurora, Colo.
²⁰ Division of Gastroenterology, Hepatology & Nutrition, University of Utah, Salt Lake City, Utah.
²¹ Department of Pediatrics, Division of Gastroenterology, Hepatology & Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill.
²² Division of Allergy and Immunology, Arkansas Children's Hospital, and the University of Arkansas for Medical Sciences, Little Rock, Ark.

PMID: 39111348
PMCID: PMC11456379
DOI: 10.1016/j.jaci.2024.07.022

Abstract

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

Keywords: Eosinophilic esophagitis; eosinophil; eosinophilic gastritis; eosinophilic gastrointestinal disease.

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Conflict of interest statement

Disclosure statement Supported by U54AI117804 (Consortium of Eosinophilic Gastrointestinal Disease Researchers), which is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Disease Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NCATS, and in part by the Division of Intramural Research, NIAID/NIH. CEGIR is also supported by patient advocacy groups including American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Diseases (CURED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by the NCATS and the National Institute of Neurological Disorders and Stroke (NINDS). B.L.W. was funded by NIH/NIAID (K23AI158813). E.M.A. was funded by the NIH (KL2TR002552, K12TR004410). S.S.A. was funded by NIH/NIDDK (R56AI092135). S.J.A. was funded by NIH/National Heart, Lung, and Blood Institute (NHLBI) (R01HL153170). D.A.H. was directly supported by the Hartwell Foundation, the Food Allergy Fund, and a faculty development award from the American Academy of Allergy, Asthma & Immunology. Allergy research in the Hill laboratory was supported by NIH/NHLBI (R01HL162715) and the Children’s Hospital of Philadelphia Research Institute. J.W.C. was supported by the NIH (K23DK129784). F.L.K. was funded by APFED HOPE Pilot Grant 2023 and NIH/NIAID K23AI171085. M.A.R. was funded by the NIH (K08AI148456). L.A.S. was supported by NIH/NIAID (R01AI168134). The contents are those of the authors and do not necessarily represent the official views or an endorsement by the NIH or other funders. None of the funding sources had a role in the design or conduct of the study. Disclosure of potential conflict of interest: B. L. Wright reports in-kind support from Regeneron in the form of study drug (dupilumab and placebo) for a clinical trial of milk oral immunotherapy. J. P. Abonia reports receipt of payment or honoraria for lectures from Takeda Global Research and Development; participation on a data safety monitoring board for OctaPharma USA; and receipt of grants or contracts from Cures Within Reach and Celgene. E. M. Abud is coinventor of patent WO/2018/160496 (microglia differentiation and use); serves as advisory board member and consulting agreements with StemPharm and Neucyte; and reports advisory board participation for Amgen and AstraZeneca. S. S. Aceves is coinventor of oral viscous budesonide, patented by the University of California, San Diego, and licensed by Takeda (oral budesonide suspension); has acted as speaker for Regeneron/Sanofi; and has received research funding from Bristol Myers Squibb. S. J. Ackerman is chief science officer and executive board member of EnteroTrack; has received patents on the Esophageal String Test (EST); has consulted for Areteia Pharmaceuticals; and has participated on the medical advisory panel of the American Partnership for Eosinophilic Disorders (APFED). M. Braskett reports acting as scientific advisor to Bryn Pharma; and receipt of royalties from UpToDate. J. W. Chang reports consulting for Regeneron/Sanofi, Takeda, and Bristol Myers Squibb. M. Chehade reports consulting for Regeneron/Sanofi, Adare/Ellodi, AstraZeneca, Bristol Myers Squibb, Allakos, Shire/Takeda, Phathom, and Recludix Pharma; and receipt of research funding from Regeneron, Allakos, AstraZeneca, Adare/Ellodi, Bristol Myers Squibb, Danone, and Shire/Takeda. G. M. Constantine reports speaker honoraria from PeerView CME. C. M. Davis reports research funding from NIH/NIAID, DBV, Regeneron, AstraZeneca, Takeda, and Allergenis; and educational funding from Genentech. E. S. Dellon reports research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda; consulting for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Bryn, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; and receipt of educational grants from Allakos, Aqilion, Holoclara, and Invea. R. Durban reports consulting for Sanofi, AstraZeneca, Reckitt/Mead Johnson Nutrition, Abbott Nutrition, and Nutricia North America. D. A. Hill has received a patent related to the utilization of food-specific T-cell responses for the diagnosis and management of EoE. E. T. Jensen reports consulting fees from Regeneron, Jazz Pharmaceuticals, and TARGET-RWE. A. Kewalramani reports sitting on the Sanofi Mid-Atlantic Regional Respiratory Field medical advisory board. P. Khoury and A. D. Klion report royalties from UpToDate. F. L. Kuang reports research funding from AstraZeneca. E. C. McGowan reports funding from NIH/NIAID and American College of Gastroenterology; and consulting for Regeneron/Sanofi and Takeda. J. M. Spergel reports grant support from the NIH, Regeneron/Sanofi, and Novartis; and has consulted for Regeneron/Sanofi, Allakos, Readysetfood, Novartis, and Bristol Myers Squibb. A. M. Uchida reports consulting for Regeneron/Sanofi, Takeda, and AstraZeneca. J. B. Wechslerc reports consulting for Allakos, Ellodi, Regeneron/Sanofi/Genzyme, Bristol Myers Squibb, Invea Therapeutics, CellDex, and AstraZeneca; and clinical trial/research funding from Allakos and Regeneron/Sanofi. R. D. Pesek reports consulting for Regeneron. The rest of the authors declare that they have no relevant conflicts of interest.

Figures

**Figure 1.. Lipidomic analysis of esophageal epithelium reveals unique sphingolipid profile in EoE**
Quantitative lipidomics were performed via mass spectroscopy on esophageal brushing samples from 14 controls with normal histology and 7 individuals with EoE (≥ 15 eos/hpf) from a medication-naïve pediatric cohort. The expression of inflammatory mediators and lipid biosynthesis enzymes was examined by RT-qPCR in esophageal biopsy samples. Non-hydroxy fatty acid sphingosine (NS) ceramides and their precursors, non-hydroxy fatty acid dihydrosphingosine (NDS) ceramides were significantly increased in EoE, with a concomitant decrease in non-hydroxy fatty acid phytoceramides (NP), resulting in selectively increased NS/NP ceramide ratios as compared to controls. Individuals with EoE had notably decreased expression of DEGS1 and DEGS2, the enzymes involved in the biosynthesis of NS and NP ceramides. The NS/NP ceramide ratio correlated strongly with IL-5 and IL-13 mRNA expression. These unique alterations in sphingolipid composition and biosynthesis likely contribute to esophageal epithelial barrier dysfunction in EoE. Created with Biorender.com Abbreviations: RT-qPCR - reverse transcription-quantitative polymerase chain reaction; NS ceramide - non-hydroxy fatty acid sphingosine ceramide; NDS ceramide - non-hydroxy fatty acid dihydrosphingosine ceramide; NP ceramide - non-hydroxy fatty acid sphingosine phytoceramide; DEGS1 - Delta 4-desaturase, sphingolipid 1; DEGS2 - Delta 4-desaturase, sphingolipid 2

**Figure 2.. Evaluation of elevated serum tryptase among individuals with eosinophilic gastrointestinal diseases (EGIDs).**
Participants (n=85) with EGID and a measured serum tryptase were examined, genomic DNA was isolated and digital droplet PCR (ddPCR) performed to determine tryptase genotypes (TPSAB1 and TPSB2) and to screen for JAK2 p.V617F and KIT p.D816V variants associated with clonal myeloid disorders. Elevated BST (≥11.4 ng/mL) was observed in 17.6% of individuals with EGID (n=15/85). Of the 15 EGID individuals with elevated BST, two were diagnosed with an underlying myeloid neoplasm responsive to tyrosine kinase inhibition. Of the remaining thirteen individuals, five had increased TPSAB1 copy number, ddPCR detected *JAK2* V617F in four individuals and *KIT* D816V in another. Somatic and mosaic variant calling analysis identified multiple variants of interest that are under further investigation. Additional studies are ongoing to determine the underlying cause for elevated BST in the remaining individuals with EGID. Created with Biorender.com. Abbreviations: EGID – eosinophilic gastrointestinal disease; ddPCR - digital droplet PCR; BST - basal serum tryptase

See this image and copyright information in PMC

References

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1. Papadopoulou A, Amil-Dias J, Auth MK, Chehade M, Collins MH, Gupta SK, et al. Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr 2024; 78:122–52. - PubMed
1. Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology 2018; 154:319–32 e3. - PMC - PubMed
1. Chehade M, Wright BL, Atkins D, Aceves SS, Ackerman SJ, Assa’ad AH, et al. Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma & Immunology Meeting. J Allergy Clin Immunol 2023; 152:1382–93. - PMC - PubMed
1. Doyle AD, Masuda MY, Kita H, Wright BL. Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions. Front Immunol 2020; 11:603295. - PMC - PubMed

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Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting

Affiliations

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting

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Abstract

Conflict of interest statement

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