Eosinophilic esophagitis versus proton pump inhibitor–responsive esophageal eosinophilia: Transcriptome analysis Tetsuo Shoda, MD, PhD, Akio Matsuda,

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Eosinophilic esophagitis versus proton pump inhibitor–responsive esophageal eosinophilia: Transcriptome analysis Tetsuo Shoda, MD, PhD, Akio Matsuda, PhD, Ichiro Nomura, MD, PhD, Naoko Okada, PhD, Kanami Orihara, PhD, Hironobu Mikami, MD, Norihisa Ishimura, MD, PhD, Shunji Ishihara, MD, PhD, Kenji Matsumoto, MD, PhD, Yoshikazu Kinoshita, MD, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 6, Pages 2010-2013.e4 (June 2017) DOI: 10.1016/j.jaci.2016.11.028 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Expression profiles of esophageal biopsies and microarray analysis. A, Unsupervised principal-component analysis of esophageal eosinophilia (EoE and PPI-REE) and the controls. B, Venn diagrams comparing the number of genes identified as dysregulated in both EoE and PPI-REE, each primarily compared with control. C, Heatmap of 2097 differentially dysregulated genes' expression profiles (P < .05, >2-fold). Clustering analysis within each group; each column represents an individual patient or control. D, Gene ontology analysis of each EoE and PPI-REE transcriptome. Journal of Allergy and Clinical Immunology 2017 139, 2010-2013.e4DOI: (10.1016/j.jaci.2016.11.028) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Comparison between EoE and PPI-REE transcriptome genes identified by microarray analysis. Spearman correlation comparing absolute raw values for all genes subjected to microarray (A), all transcription factor gene expression levels (B), and the 2097 differentially dysregulated genes (C). Black, P < .05, >2-fold; orange, EoE diagnostic panel gene. D, E, and F, Eotaxin-3 (CCL26) mRNA expression, esophageal eosinophil counts, and KCNJ2 mRNA expression in indicated groups are shown (****P < .0001, ***P = .001, and **P < .01). PPI-REE post, Post-PPI treated patients. Journal of Allergy and Clinical Immunology 2017 139, 2010-2013.e4DOI: (10.1016/j.jaci.2016.11.028) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Comparison of esophageal transcriptomes using 2097 genes. A, Heatmap showing 2097 differentially dysregulated gene expression profiles (P < .05, >2-fold). Clustering analysis within each group was performed; each column represents an individual patient or control. B, Correlations between the CCL26 level and eosinophil count for all the samples included in this study (r = 0.91; P < .0001). Journal of Allergy and Clinical Immunology 2017 139, 2010-2013.e4DOI: (10.1016/j.jaci.2016.11.028) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions