Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois Bruce K. Tan, MD, MS, Aiko I. Klingler, PhD,

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Presentation transcript:

Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois Bruce K. Tan, MD, MS, Aiko I. Klingler, PhD, Julie A. Poposki, MS, Whitney W. Stevens, MD, PhD, Anju T. Peters, MD, Lydia A. Suh, BS, James Norton, MS, Roderick G. Carter, BS, Kathryn E. Hulse, PhD, Kathleen E. Harris, BS, Leslie C. Grammer, MD, Robert P. Schleimer, PhD, Kevin C. Welch, MD, Stephanie S. Smith, MD, David B. Conley, MD, Robert C. Kern, MD, Atsushi Kato, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 2, Pages 699-703.e7 (February 2017) DOI: 10.1016/j.jaci.2016.06.063 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Messenger RNAs for markers of type 2 and 3 inflammation were elevated in patients with CRSsNP. Total RNA was extracted from whole tissue of control IT (n = 19), control UT (n = 21), control ET (n = 33), CRSsNP IT (n = 53), CRSsNP UT (n = 44), CRSsNP ET (n = 61), CRSwNP IT (n = 28), CRSwNP UT (n = 29), CRSwNP ET (n = 40), and CRSwNP NP (n = 48). Expression of mRNAs for IFN-γ, CLC, IL-5, IL-13, and IL-17A was analyzed using real-time RT-PCR. Gene expression was normalized to a housekeeping gene, β-glucuronidase (GUSB), and expression levels were shown as % expression of GUSB. Results are shown as medians (25% to 75% interquartile ranges) (A and B) or mean ± SEM (C). Dotted line indicates the threshold based on the 95th percentile expression in control ET (CLC, 96.4; IL-5, 36.5; IL-13, 11.2; IFN-γ, 13.2; IL-17A, 12.1) (Fig 1, C). To display undetectable data, we plotted 0 as 0.01 in log-scaled figures (Fig 1, C). *P < .05, ***P < .001, ****P < .0001, by 1-way ANOVA. Journal of Allergy and Clinical Immunology 2017 139, 699-703.e7DOI: (10.1016/j.jaci.2016.06.063) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Type 2 and 3 cytokines were elevated in CRSsNP tissue protein extracts. Protein extracts were generated from ET of control (n = 34), CRSsNP (n = 83), CRSwNP (n = 45), and NPs (n = 60). Expression of ECP, IL-5, IL-13, IFN-γ, and IL-17A proteins in tissue homogenates was measured using ELISA and Luminex. The protein concentrations were normalized to the concentration of total protein. Dotted line indicates the threshold based on the 95th percentile expression in control ET (ECP, 131.5 ng/mg; IL-5, 0.02 pg/mg [detectable]; IL-13, 5.5 pg/mg; IFN-γ, 8.1 pg/mg; IL-17A, 0.02 pg/mg [detectable]). To display undetectable data, we plotted 0 as 0.01 in log-scaled figures. *P < .05, **P < .01, ***P < .001, ****P < .0001, by 1-way ANOVA. Journal of Allergy and Clinical Immunology 2017 139, 699-703.e7DOI: (10.1016/j.jaci.2016.06.063) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Diagram of nasal and paranasal sinuses. Illustrative computed tomography (CT) images demonstrating the anatomic location of studied tissue from (A) a patient with typical changes of CRSwNP on one side but more normal anatomy on the contralateral side and (B) a patient with radiographic changes typical for CRSsNP. Journal of Allergy and Clinical Immunology 2017 139, 699-703.e7DOI: (10.1016/j.jaci.2016.06.063) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Expression of IL-5, IL-13, and IL-17A in IT, UT, and ET. Total RNA was extracted from whole tissue of control IT (n = 19), control UT (n = 21), control ET (n = 33), CRSsNP IT (n = 53), CRSsNP UT (n = 44), CRSsNP ET (n = 61), CRSwNP IT (n = 28), CRSwNP UT (n = 29), and CRSwNP ET (n = 40). Expression of mRNAs for IL-5, IL-13, and IL-17A was analyzed using real-time RT-PCR. Gene expression was normalized by a housekeeping gene, GUSB, and expression levels were shown as % expression of GUSB. Results are shown as medians (25% to 75% interquartile ranges). *P < .05, **P < .01, and ***P < .001, by 1-way ANOVA. Journal of Allergy and Clinical Immunology 2017 139, 699-703.e7DOI: (10.1016/j.jaci.2016.06.063) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 CRSsNP can be divided into several groups. Total RNA was extracted from whole tissue of control ET (n = 33), CRSsNP ET (n = 61), CRSwNP ET (n = 40), and CRSwNP NP (n = 48). CRSsNP was further divided into type 1 cytokine high group (n = 5), type 2 cytokine high group (n = 17), type 3 cytokine high group (n = 4), type 1 and 2 cytokines high group (type 1/2, n = 4), type 1 and 3 cytokines high group (type 1/3, n = 4), type 1, 2, and 3 cytokines high group (type 1/2/3, n = 1), and type 1, 2, and 3 cytokine all low group (all low, n = 26). Type 1, 2, and 3 high groups were classified on the basis of 95th percentile expression of IFN-γ (13.2), CLC (96.4), and IL-17A (12.1), respectively, in control ET. Expression of mRNAs for CLC, IL-5, IL-13, and IFN-γ was analyzed using real-time RT-PCR. Gene expression was normalized to a housekeeping gene, GUSB, and expression levels were shown as % expression of GUSB. Results are shown as mean ± SEM. To display undetectable data, we plotted 0 as 0.01 in log-scaled figures. Journal of Allergy and Clinical Immunology 2017 139, 699-703.e7DOI: (10.1016/j.jaci.2016.06.063) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Subclassification of CRSsNP by protein levels of type 2 and 3 cytokines. Protein extracts were generated from whole ET tissues of control (n = 34), CRSsNP (n = 83), CRSwNP (n = 45), and NP tissues (n = 60). CRSsNP was further divided into type 2 cytokine high group (n = 31), type 3 cytokine high group (n = 6), type 2 and 3 cytokines high group (type 2/3, n = 7), and type 2 and 3 cytokines all low group (all low, n = 39). Expression of ECP, IL-5, IL-13, IFN-γ, and IL-17A proteins in tissue homogenates was measured using ELISA and Luminex and normalized to the concentration of total protein. Type 2 and 3 high groups were classified on the basis of 95th percentile expression of ECP (131.5 ng/mg) and IL-17A (0.02 pg/mg [detectable]), respectively, in control ET. To display undetectable data, we plotted 0 as 0.01 in log-scaled figures. Journal of Allergy and Clinical Immunology 2017 139, 699-703.e7DOI: (10.1016/j.jaci.2016.06.063) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions