Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome

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Presentation transcript:

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome Julie M. Caldwell, PhD, Margaret H. Collins, MD, Emily M. Stucke, BA, Philip E. Putnam, MD, James P. Franciosi, MD, MS, MSCE, Jonathan P. Kushner, MD, J. Pablo Abonia, MD, Marc E. Rothenberg, MD, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 5, Pages 1114-1124 (November 2014) DOI: 10.1016/j.jaci.2014.07.026 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Gastric tissue of patients with EG displays marked eosinophilic inflammation that correlates with peripheral blood eosinophil counts. A and B, Peripheral eosinophil counts (103/μL; Fig 1, A) and eosinophil percentages (Fig 1, B) within peripheral blood leukocytes (control subjects, n = 9; patients with EG, n = 15). C, Example of gastric nodules in a patient with EG. D, Hematoxylin and eosin–stained gastric antrum biopsy specimen of a patient with EG (patient 19; ×200 magnification). Eosinophils densely populate the lamina propria, forming sheets (arrows). E, Peak gastric antrum tissue eosinophil counts (control subjects, n = 15; patients with EG, n = 15). F, The peak gastric tissue eosinophil count was correlated with the absolute peripheral eosinophil count (103/μL; patients 1-30, if available [n = 9 control subjects, n = 15 patients with EG]). Pearson r2 = 0.8102, P < .0001. For Fig 1, A, B, and E, data are expressed as means ± SEMs and were analyzed by using the unpaired t test. **P < .01 and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Gastric tissue from a patient with EG exhibits increased levels of proliferating cells and FOXP3+ cells. Gastric antrum sections obtained during the index endoscopy (patients 1-5 and 16-20, as defined in Table E1) were stained with antibodies against the indicated protein. Representative photographs (×200 magnification) of MIB-1–stained (A and B) and FOXP3-stained (C and D) gastric tissue from control subjects and patients with EG are shown. Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Gastric tissue of patients with EG exhibits a conserved pattern of gene expression. A, Microarray data (patients 1-5 [control subjects] and 16-20 [patients with EG]) were analyzed by using a volcano plot. Transcripts of interest are denoted (top panel). B, The number of transcripts that exhibit the indicated minimum fold difference in patients with EG versus control subjects is graphed. Transcripts (n = 32) with 5-fold or greater change (ie, ≥5 or ≤0.2) are listed. C, Expression values for individual patients (n = 104 transcripts; P < .01 and ≥2-fold change). Patient numbers correspond to those in Table E1. D, The 41 transcripts common to the EG transcriptome (1709 transcripts) and the EoE transcriptome are shown. E and F, The 30 most upregulated (Fig 3, E) and downregulated (Fig 3, F) transcripts in the EG transcriptome are listed along with the corresponding relative fold change in expression in tissue from patients with EoE versus control tissue. Affy probe ID, Affymetrix probe set ID number; CTL, control. Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Gastric tissue from patients with EG exhibits a conserved pattern of cytokine gene expression. Relative gastric antrum cytokine transcript levels (mean ± SEM; A, IL4; B, IL5; C, IL17; and D, IL33) were determined for patients 6 to 15 (control subjects) and 21 to 30 (patients with EG). *P < .05, **P < .01, and ***P < .001. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Expression of IL13 and CCL26 is increased in gastric tissue from patients with EG. A and B, Relative gastric antrum transcript levels (means ± SEMs) of IL13 (patients 1-5 [control subjects] and 16-20 [patients with EG]; Fig 5, A) and CCL26 (patients 6-15 [control subjects] and 21-30 [patients with EG]; Fig 5, B). C, Normalized CCL26 transcript levels were correlated with normalized IL13 levels (patients 6-15 [control subjects] and 21-30 [patients with EG]). D and E, Normalized CCL26 transcript levels (patients 1-5 [control subjects] and 16-20 [patients with EG]) were correlated with average gastric tissue eosinophil counts (Fig 5, D) and peak gastric tissue eosinophil counts (Fig 5, E). For Fig 5, C-E, Pearson r2 and P values are shown in boldface; Spearman r and P values are in italics. *P < .05 and ***P < .001. NS, Not significant; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 Journal of Allergy and Clinical Immunology 2014 134, 1114-1124DOI: (10.1016/j.jaci.2014.07.026) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions