Large-scale gene expression profiling reveals distinct type 2 inflammatory patterns in chronic rhinosinusitis subtypes Matthew A. Tyler, MD, Chris B.

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Presentation transcript:

Large-scale gene expression profiling reveals distinct type 2 inflammatory patterns in chronic rhinosinusitis subtypes Matthew A. Tyler, MD, Chris B. Russell, PhD, Dirk E. Smith, MSc, James B. Rottman, DVM, PhD, Caroline J. Padro Dietz, PhD, Xuguang Hu, PhD, Martin J. Citardi, MD, Samer Fakhri, MD, Shervin Assassi, MD, Amber Luong, MD, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 3, Pages 1061-1064.e4 (March 2017) DOI: 10.1016/j.jaci.2016.09.048 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Expression of canonical type 2 inflammatory markers in CRS subtypes. A, Expression of IgE. Samples from each disease subtype are stratified according to presence or absence of asthma phenotype. B, Relative expression of several canonical upstream regulators of type 1 (IFN-γ) or type 2 inflammation (IL-4, IL-5, IL-13) as measured by droplet digital PCR. C and D, Relative expression of important downstream type 2 inflammatory gene clusters. POSTN, Periostin. †P < .05, *P < .01, **P < .001 for comparisons of HC versus each subtype. When no annotation is indicated, the comparison was not significant. Journal of Allergy and Clinical Immunology 2017 139, 1061-1064.e4DOI: (10.1016/j.jaci.2016.09.048) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 ILRL1 expression and mast cell activity in CRS. A, Box and whisker plot of differential expression of IL1RL1 by microarray analysis. B, Correlation of IL1RL1 and tryptase gene cluster. r2 = 0.46, P < .001. C and D, IL-33 expression and mast cell and eosinophil infiltration in representative CRSwNP tissue. Fig 2, C, Representative photomicrograph illustrating IL-33 expression located in the nasal surface epithelium (black arrow) as well as the stroma (blue arrow) containing inflammatory infiltrate. Fig 2, D, Photomicrographs demonstrating the expression of IL-33 associated with varying levels of eosinophil and mast cell infiltration. MBP, Major basic protein. **P < .001 for comparisons of HC versus each subtype. When no annotation is indicated, the comparison was not significant. Journal of Allergy and Clinical Immunology 2017 139, 1061-1064.e4DOI: (10.1016/j.jaci.2016.09.048) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Hierarchical gene expression cluster analysis in CRS subtypes. Ward's linkage analysis was used to organize the 32,719 sequences into 500 clusters that are represented by the dendrogram with arbitrarily colored columns across the top of the heat map. Changes with log2 (FC) ≥2 are bright red (highly upregulated) and those with log2 (FC) ≤2 are bright green (highly downregulated). The separation of CRS subtypes according to their differential gene cluster expression is illustrated on the right of the heat map. Journal of Allergy and Clinical Immunology 2017 139, 1061-1064.e4DOI: (10.1016/j.jaci.2016.09.048) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions