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Journal of Allergy and Clinical Immunology

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Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study - 05/01/20

Doi : 10.1016/j.jaci.2019.11.007 
Tetsuo Shoda, MD, PhD a, Ting Wen, PhD a, Julie M. Caldwell, PhD a, Margaret H. Collins, MD b, John A. Besse, BS a, Garrett A. Osswald, BS a, J. Pablo Abonia, MD a, Nicoleta C. Arva, MD, PhD c, Dan Atkins, MD d, Kelley E. Capocelli, MD e, Evan S. Dellon, MD, MPH f, Gary W. Falk, MD, MS g, Nirmala Gonsalves, MD h, Sandeep K. Gupta, MD i, Ikuo Hirano, MD h, Vincent A. Mukkada, MD j, Philip E. Putnam, MD j, Rachel M. Sheridan, MD b, Amanda K. Rudman Spergel, MD k, Jonathan M. Spergel, MD, PhD l, Joshua B. Wechsler, MD, PhD m, Guang-Yu Yang, MD, PhD n, Seema S. Aceves, MD, PhD o, Glenn T. Furuta, MD p, Marc E. Rothenberg, MD, PhD a, ⁎
on behalf of the

Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)∗

  The list of participants is provided in this article’s Online Repository at www.jacionline.org.

a Division of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 
b Division of Pathology, University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 
j Division of Gastroenterology, Hepatology, and Nutrition, University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 
c Department of Pathology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Chicago, Ill 
h Division of Gastroenterology & Hepatology, Northwestern University, Feinberg School of Medicine, Chicago 
n Department of Pathology and Laboratory Medicine, Northwestern University, Evanston, Ill 
d Section of Pediatric Allergy and Immunology, Children’s Hospital Colorado, Aurora, Colo 
e Department of Pathology, Children’s Hospital Colorado, Aurora, Colo 
f Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC 
g Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa 
i Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine/Children's Hospital of Illinois, Peoria, Ill 
k Allergy, Asthma and Airway Biology Branch, Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md 
l Division of Allergy and Immunology, University of Pennsylvania Perelman School of Medicine/Children's Hospital of Philadelphia, Pa 
m Gastroenterology, Hepatology & Nutrition, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Ill 
o Division of Allergy Immunology, University of California–San Diego, and Rady Children’s Hospital, San Diego, Calif 
p Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, Aurora, Colo 

∗Corresponding author: Marc E. Rothenberg, MD, PhD, Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Ave, ML 7028, Cincinnati, OH 45229.Division of Allergy and ImmunologyCincinnati Children’s Hospital Medical CenterDepartment of PediatricsUniversity of Cincinnati College of Medicine3333 Burnet AveML 7028CincinnatiOH45229

Abstract

Background

Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools.

Objective

We aimed to develop tissue- and blood-based diagnostic platforms for EG.

Methods

Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers–associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels.

Results

Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = −0.83, P < .0001), periglandular circumferential collars (r = −0.73, P < .0001), and endoscopic nodularity (r = −0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP18 scores (plasma: r = −0.64, P = .0015; serum: r = −0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001).

Conclusion

We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.

Le texte complet de cet article est disponible en PDF.

Graphical abstract




Le texte complet de cet article est disponible en PDF.

Key words : Biomarker, diagnostic panel, eosinophil, eosinophilic gastritis, transcriptome

Abbreviations used : AUC, CCHMC, CEGIR, CT, EG, EGDP, EGID, EoE, FDR, GAPDH, hpf, IL-4R, ROC, TARC, TSLP


Plan


 This study was supported by Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR; U54 AI117804), which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is cofunded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Center for Advancing Translational Sciences (NCATS). CEGIR is also supported by patient advocacy groups including the American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC).
 Disclosure of potential conflict of interest: M. H. Collins is a consultant for Shire, Regeneron, Receptos, and Esocap and has received research funding from Shire, Regeneron, and Receptos. E. S. Dellon is a consultant for Adare, Alivio, Allakos, AstraZeneca, Banner, Biorasi, Calypso, Enumeral, EsoCap, Gossamer Bio, GlaxoSmithKline, Receptos/Celegene, Regeneron, Salix, and Shire; has received research funding from Adare, Allakos, GlaxoSmithKline, Meritage, Miraca, Nutricia, Receptos/Celgene, Regeneron, and Shire; and has received educational grants from Allakos, Banner, and Holoclara. G. W. Falk has received research support from Celgene/Receptos, Regeneron, Takeda/Shire, and Adare and is a consultant for Adare and Takeda/Shire. N. Gonsalves is a consultant for Allakos. S. K. Gupta is a consultant for Abbott, Adare, Allakos, QOL, and Receptos/Celgene and receives research support from Shire. I. Hirano is a consultant for Regeneron, Receptos, Shire, Allakos, and Adare and has received research funding from Regeneron, Receptos, Shire, and Adare. V. A. Mukkada is a consultant for Shire and has received research funding from Shire. T. Shoda has received research support from JSPS Overseas Research Fellowships and is a co-inventor of patents owned by Cincinnati Children's Hospital Medical Center. J. M. Spergel is a consultant for Regeneron and DBV Technology, and his research is supported by the National Institutes of Health, the Everybody Eats (EATS) Foundation, Aimmune Therapeutics, Food Allergy Research & Education (FARE), and DBV Technology. J. B. Wechsler is a consultant for Allakos. S. S. Aceves is a consultant for Regeneron, Aimmune Therapeutics, and Gossamer; is an inventor of oral viscous budesonide, patented by UCSD and licensed by Shire/Takeda; and has research funding from the Ferring Research Institute. G. T. Furuta is a consultant for Shire and a cofounder of EnteroTrack. M. E. Rothenberg is a consultant for PulmOne, Spoon Guru, Celgene, Shire, Astra Zeneca, GlaxoSmithKline, Allakos, Adare, Regeneron, and Novartis; has an equity interest in PulmOne, ClostaBio, and Spoon Guru; receives royalties from reslizumab (Teva Pharmaceuticals); and is an inventor of patents owned by Cincinnati Children’s. The rest of the authors declare that they have no relevant conflicts of interest.


© 2019  American Academy of Allergy, Asthma & Immunology. Tous droits réservés.
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Vol 145 - N° 1

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