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Background: Eosinophilic esophagitis (EoE) involves a chronic immune‐mediated response to dietary antigens. Recent work identifies T‐cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food‐specific T‐cell repertoire. We sought to confirm T‐cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. Methods: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non‐EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V‐J‐CDR3s were assessed based on specific food triggers. Results: Active EoE biopsies from children but not adults displayed decreased unique TCRα/β clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non‐EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre‐diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). Conclusion: We confirmed relative clonality in children but not adults with active EoE and identified potential food‐specific TCRs, particularly for milk‐triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers. [ABSTRACT FROM AUTHOR]

Abbreviations CCHMC Cincinnati Children's Hospital Medical Center CEGIR Consortium of Eosinophilic Gastrointestinal Disease Researchers EDP eosinophilic esophagitis diagnostic panel EoE eosinophilic esophagitis HPF high-power field MC Mast cells; PRO, Patient-reported outcome EEsAI eosinophilic esophagitis activity index PEESS Pediatric Eosinophilic Esophagitis Symptom Scores HSS EoE Histology Scoring System EREFS EoE endoscopic reference score CONFLICT OF INTEREST M.E.R. is a consultant for Pulm One, Spoon Guru, Allakos, ClostraBio, Serpin Pharm, Celgene, Shire, AstraZeneca, GlaxoSmithKline, Allakos, Adare, Regeneron, and Novartis and has an equity interest in the first five, as well as royalties from reslizumab (Teva Pharmaceuticals) and UpToDate. Mast cells (MCs) are involved in allergy, including EoE,2 and neuromodulation.3 MCs reside in peripheral tissue and communicate with nearby structures, including nerve endings. We divided active EoE into four quartiles by using I CPA3 i + I HPGDS i sum as a MC count surrogate marker; the highest and lowest quartiles represented MC-high and MC-low, respectively. [Extracted from the article]

Keywords: mast cells; COVID; inflammation; innate immunity; long covid EN mast cells COVID inflammation innate immunity long covid 1288 1291 4 03/30/22 20220401 NES 220401 ACKNOWLEDGEMENTS Professional writing and editing support was provided by Jocelyn Hybiske, PhD, an independent consultant, funded by Allakos. (E-G) Levels of cytokines and mast cell-derived proteases in sera from PASC patients (light blue; n = 13), acute COVID-19 patients (red; n = 19), or controls (gray; n = 19-20). Mast cell activation is associated with post-acute COVID-19 syndrome. [Extracted from the article]