Esophageal type 2 cytokine expression heterogeneity in eosinophilic esophagitis in a multisite cohort - 08/06/20
on behalf of the
Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)‡
Abstract |
Background |
There is strong evidence for a role of type 2 cytokines in the pathogenesis of eosinophilic esophagitis (EoE); however, heterogeneity in type 2 gene expression has not been examined.
Objective |
We examined type 2 immunity–associated gene expression in esophageal biopsy specimens, aiming to determine the degree of cytokine heterogeneity and its potential clinical significance.
Methods |
Patients (n = 312) were recruited from 10 sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. In addition to histologic and endoscopic assessment, esophageal biopsy specimens were examined for expression of 96 genes within the EoE diagnostic panel.
Results |
Five subgroups of patients with active EoE were identified by unsupervised clustering based on expression of IL4, IL5, IL13, C-C motif chemokine ligand 26 (CCL26), thymic stromal lymphopoietin (TSLP), Charcot-Leyden crystal (CLC), C-C motif chemokine receptor 3 (CCR3), and CPA3. These groups differed in age (P < .02) and EoE diagnostic panel score (P < 1.08E–30) but not in eosinophil levels. The group V patients had the highest expression of IL5, TSLP, and CCL26 and genes associated with tissue remodeling, such as COL8A1, actin γ-2 (ACTG2), and tetraspanin 12 (TSPAN12). IL5 and IL13 were highly expressed in group IV; however, groups IV and V differed in age (34 vs 14 years [P < .05]). Groups II and III, which exhibited intermediate expression of IL5 and CPA3, were differentiated by high TSLP and IL13 in group III.
Conclusion |
We observed heterogeneous type 2 gene expression among patients with active EoE. Type 2 gene overexpression was not directly proportional to disease features; this was especially true for tissue remodeling events. These findings highlight a clinical opportunity for leveraging molecular endotypes to implement personalized medicine in EoE.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Allergy, cytokine, eosinophil, fibrosis, IL-5, IL-13, inflammation, precision medicine, resolution, TH2 cells
Abbreviations used : ACTG2, ALOX15, BZH, CCL26, CCR3, CEGIR, CLC, COL8A2, Ct, ΔCt, DEC, DIS, DSG1, EDP, EI, EoE, EoEe, EREFS, HSS, LRRC31, MMP12, SLC26A4, SPINK7, TGFB1, TNFAIP, TSLP, TSPAN12
Plan
| CEGIR (U54 AI117804) is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences; it is cofunded by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Advancing Translational Sciences. CEGIR is also supported by patient advocacy groups, including the American Partnership for Eosinophilic Disorders and the Campaign Urging Research for Eosinophilic Disease. |
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| Disclosure of potential conflict of interest: M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, Celgene, AstraZeneca, Allakos, and ClostraBio and has an equity interest in Pulm One, Spoon Guru, and ClostraBio and royalties from reslizumab (Teva Pharmaceuticals); he is also an inventor of patents, owned by Cincinnati Children’s. G. W. Falk has received research support from Celgene/Receptos, Regeneron, Shire, and Adare. M. H. Collins is a consultant for Allakos, AstraZeneca, Esocap, Shire/Takeda, Regeneron, and Receptos/Celgene and has received research funding from Shire/Takeda, Regeneron, and Receptos/Celgene. E. S. Dellon is a consultant for Adare, Aimmune, Alivio, Allakos, AstraZeneca, Banner, Calypso, Enumeral, Esocap, Gossamer Bio, GSK, Receptos/Celegene, Regeneron, Robarts, Salix, and Shire/Takeda; the recipient of research funding from Adare, Allakos, Meritage, Miraca, Nutricia, Receptos/Celgene, Regeneron, and Shire/Takeda; and the recipient of educational grants from Allakos, Banner, and Holoclara. S. S. Aceves is a consultant for Regeneron and AImmune; an inventor of oral viscous budesonide, patented by the University of California, San Diego, and licensed by Shire; and the recipient of research funding from Ferring Research Institute. J. M. Spergel is a consultant for Regeneron and DBV Technology; his research is supported by the National Institutes of Health, EATS Foundation, AImmune Therapeutics, FARE, and DBV Technology. G. T. Furuta is a consultant for Shire and a cofounder of EnteroTrack. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 145 - N° 6
P. 1629 - juin 2020 Retour au numéro
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