Tetsuo Shoda1, Ting Wen1, Julie M Caldwell1, Margaret H Collins2, John A Besse1, Garrett A Osswald1, J Pablo Abonia1, Nicoleta C Arva3, Dan Atkins4, Kelley E Capocelli5, Evan S Dellon6, Gary W Falk7, Nirmala Gonsalves8, Sandeep K Gupta9, Ikuo Hirano8, Vincent A Mukkada10, Philip E Putnam10, Rachel M Sheridan2, Amanda K Rudman Spergel11, Jonathan M Spergel12, Joshua B Wechsler13, Guang-Yu Yang14, Seema S Aceves15, Glenn T Furuta16, Marc E Rothenberg17. 1. Division of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 2. Division of Pathology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 3. Department of Pathology, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Chicago, Ill. 4. Section of Pediatric Allergy and Immunology, Children's Hospital Colorado, Aurora, Colo. 5. Department of Pathology, Children's Hospital Colorado, Aurora, Colo. 6. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC. 7. Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. 8. Division of Gastroenterology & Hepatology, Northwestern University, Feinberg School of Medicine, Chicago. 9. Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine/Children's Hospital of Illinois, Peoria, Ill. 10. Division of Gastroenterology, Hepatology, and Nutrition, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 11. 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. 12. Division of Allergy and Immunology, University of Pennsylvania Perelman School of Medicine/Children's Hospital of Philadelphia, Pa. 13. Gastroenterology, Hepatology & Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill. 14. Department of Pathology and Laboratory Medicine, Northwestern University, Evanston, Ill. 15. Division of Allergy Immunology, University of California-San Diego, and Rady Children's Hospital, San Diego, Calif. 16. Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, Aurora, Colo. 17. Division of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Rothenberg@cchmc.org.
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.
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.
Authors: Julie M Caldwell; Margaret H Collins; Emily M Stucke; Philip E Putnam; James P Franciosi; Jonathan P Kushner; J Pablo Abonia; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2014-09-15 Impact factor: 10.793
Authors: Carine Blanchard; Ning Wang; Keith F Stringer; Anil Mishra; Patricia C Fulkerson; J Pablo Abonia; Sean C Jameson; Cassie Kirby; Michael R Konikoff; Margaret H Collins; Mitchell B Cohen; Rachel Akers; Simon P Hogan; Amal H Assa'ad; Philip E Putnam; Bruce J Aronow; Marc E Rothenberg Journal: J Clin Invest Date: 2006-02 Impact factor: 14.808
Authors: Sandeep K Gupta; Gary W Falk; Seema S Aceves; Mirna Chehade; Margaret H Collins; Evan S Dellon; Nirmala Gonsalves; Ikuo Hirano; Vincent A Mukkuda; Kathryn A Peterson; Jonathan Spergel; Guang-Yu Yang; Glenn T Furuta; Marc E Rothenberg Journal: Gastroenterology Date: 2018-11-17 Impact factor: 22.682
Authors: Andres Matoso; Vincent A Mukkada; Shaolei Lu; Renee Monahan; Kelly Cleveland; Lelia Noble; Shamlal Mangray; Murray B Resnick Journal: Mod Pathol Date: 2013-03-15 Impact factor: 7.842
Authors: K Polzer; T Karonitsch; T Neumann; G Eger; C Haberler; A Soleiman; B Hellmich; E Csernok; J Distler; B Manger; K Redlich; G Schett; J Zwerina Journal: Rheumatology (Oxford) Date: 2008-04-08 Impact factor: 7.580
Authors: K A Peterson; M Yoshigi; M W Hazel; D A Delker; E Lin; C Krishnamurthy; N Consiglio; J Robson; M Yandell; F Clayton Journal: Aliment Pharmacol Ther Date: 2018-06-04 Impact factor: 8.171
Authors: Julia L M Dunn; Tetsuo Shoda; Julie M Caldwell; Ting Wen; Seema S Aceves; Margaret H Collins; Evan S Dellon; Gary W Falk; John Leung; Lisa J Martin; Paul Menard-Katcher; Amanda K Rudman-Spergel; Jonathan M Spergel; Joshua B Wechsler; Guang-Yu Yang; Glenn T Furuta; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2020-03-19 Impact factor: 10.793
Authors: Seema Aceves; Margaret H Collins; Marc E Rothenberg; Glenn T Furuta; Nirmala Gonsalves Journal: J Allergy Clin Immunol Date: 2019-11-20 Impact factor: 10.793
Authors: Evan S Dellon; Nirmala Gonsalves; Marc E Rothenberg; Ikuo Hirano; Mirna Chehade; Kathryn A Peterson; Gary W Falk; Joseph A Murray; Lauren T Gehman; Alan T Chang; Bhupinder Singh; Henrik S Rasmussen; Robert M Genta Journal: Clin Gastroenterol Hepatol Date: 2021-06-02 Impact factor: 11.382
Authors: Elizabeth A Jacobsen; David J Jackson; Enrico Heffler; Sameer K Mathur; Albert J Bredenoord; Ian D Pavord; Praveen Akuthota; Florence Roufosse; Marc E Rothenberg Journal: Annu Rev Immunol Date: 2021-03-01 Impact factor: 28.527
Authors: Marc E Rothenberg; Shawna K B Hottinger; Nirmala Gonsalves; Glenn T Furuta; Margaret H Collins; Nicholas J Talley; Kathryn Peterson; Calies Menard-Katcher; Macie Smith; Ikuo Hirano; Robert M Genta; Mirna Chehade; Sandeep K Gupta; Jonathan M Spergel; Seema S Aceves; Evan S Dellon Journal: J Allergy Clin Immunol Date: 2021-12-22 Impact factor: 10.793
Authors: Erica J Brenner; Sydney B Greenberg; Nicole C Chang; S Ryanne Corder; Ellen L Cowherd; Evan S Dellon Journal: Clin Res Hepatol Gastroenterol Date: 2021-06-25 Impact factor: 3.189