Presentation is loading. Please wait.

Presentation is loading. Please wait.

Griet A. Van Roey, PhD, Christopher C

Published byHengki Kusnadi Modified over 5 years ago

Similar presentations

Presentation on theme: "Griet A. Van Roey, PhD, Christopher C"— Presentation transcript:

1 Classical complement pathway activation in the nasal tissue of patients with chronic rhinosinusitis 
Griet A. Van Roey, PhD, Christopher C. Vanison, MD, Jeffanie Wu, Julia H. Huang, MSc, Lydia A. Suh, BSc, Roderick G. Carter, BSc, James E. Norton, MSc, Stephanie Shintani-Smith, MD, David B. Conley, MD, Kevin C. Welch, MD, Anju T. Peters, MD, Leslie C. Grammer, MD, Kathleen E. Harris, BSc, Kathryn E. Hulse, PhD, Atsushi Kato, PhD, Whitney W. Stevens, MD, PhD, Robert C. Kern, MD, Robert P. Schleimer, PhD, Bruce K. Tan, MD, MSc  Journal of Allergy and Clinical Immunology  Volume 140, Issue 1, Pages e2 (July 2017) DOI: /j.jaci Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 The complement activation pathway. The 3 major pathways of complement activation, classical, lectin, and alternative, all lead to formation of C3 convertases, which lead to generation of the anaphylatoxins C3a and C5a and formation of the lytic membrane attack complex (C5b-9). We evaluated the complement activation neoepitopes highlighted by the boxes. Anaphylatoxin C5a was also evaluated. Dotted arrows indicate enzymatic processes. MASP, MBL-associated serine protease; MBL, mannose-binding lectin.14 Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Levels of complement activation products C5b-9, C4d, and C1rs-C1inh were increased in NPs compared with UT. Tissue homogenates were tested by means of ELISA, and levels were normalized to total protein for C5b-9 (A), C4d (B), and C1rs-C1inh (C). Data represent means ± SEMs. *P < .05, **P < .01, ***P < .001, and ****P < .0001, Kruskal-Wallis test. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Complement components C5b-9 and C4d are deposited linearly along the basement membrane of the nasal epithelium. OCT-embedded tissue sections were stained for C5b-9 in red (A, C, E, and F), C4d in green (B, D, and E), and laminin in green (F and G). Representative image of NP tissue. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Percentage of nasal epithelium lined with complement. Stitched whole-tissue section images were analyzed for positive subepithelial C5b-9 staining with ImageJ software and represented as a percentage of the length of epithelium visualized. Data represent means ± SEMs. *P < .05 and ***P < .001, Kruskal-Wallis test. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Correlations between complement-fixing antibody isotypes and C1rs-C1inh activation product of the classical pathway in NP tissue. A, Correlation between IgM and C1rs-C1inh levels. B, Correlation between IgG3 and C1rs-C1inh levels. C, Correlation between IgG1 and C1rs-C1inh levels. D, Correlation between IgG2 and C1rs-C1inh levels. E, Correlation between IgG4 and C1rs-C1inh levels. F, Correlation between total immunoglobulin and C1rs-C1inh levels. The Spearman coefficient was used for analysis. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 C5a levels in sinonasal tissue and correlations with complement activation products. A, Levels of C5a. B, Correlation between C1rs-C1inh and C5a levels. C, Correlation between C4d and C5a levels. D, Correlation between C5b-9 and C5a levels. E, Correlations between activated C1, C4d, C5b-9, and C5a with ECP and anti-dsDNA IgG levels. The Spearman coefficient was used for analysis. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 7 Increased levels of anti–basement membrane antibodies in NP tissue. Antibodies were purified from NP tissue homogenates and compared with antibodies purified from serum from the same patients with CRSwNP and control subjects. Total extracted antibody (5 μg/mL) were tested on an anti-Matrigel ELISA. Data represent means ± SEMs. ****P < .0001, Kruskal-Wallis test. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E1 Complement component C5b-9, C4d, and C1rs-C1inh levels in sinonasal tissue correlated moderately but significantly. Correlation between C4d and C1rs-C1inh levels (A); correlation between C4d and C5b-9 levels (B); and correlation between C1rs-inh and C5b-9 levels measured in sinonasal tissue homogenates (C). Correlations were assessed by using the nonparametric Spearman rank correlation coefficient. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "Griet A. Van Roey, PhD, Christopher C"

Similar presentations

Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy Yitzhak Katz, MD, Nelly Rajuan, MSc, Michael R. Goldberg,

Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy Yitzhak Katz, MD, Nelly Rajuan, MSc, Michael R. Goldberg,
Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: A double-blind randomized controlled trial Saifudin.

Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: A double-blind randomized controlled trial Saifudin.
Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease  Merja T. Augustin, MD, Jorma Kokkonen, MD,

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease  Merja T. Augustin, MD, Jorma Kokkonen, MD,
Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric.

Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric.
Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B

Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B
Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease  Merja T. Augustin, MD, Jorma Kokkonen, MD,

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease  Merja T. Augustin, MD, Jorma Kokkonen, MD,
High-titer IgE antibody specific for pollen allergens in northern California is associated with both wheezing and total serum IgE  Elizabeth A. Erwin,

High-titer IgE antibody specific for pollen allergens in northern California is associated with both wheezing and total serum IgE  Elizabeth A. Erwin,
Striking deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis  Jens U. Ponikau, MD, David A. Sherris,

Striking deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis  Jens U. Ponikau, MD, David A. Sherris,
Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema  Sabine Zeller, MSc, Claudio Rhyner, PhD, Norbert Meyer, MD, Peter.

Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema  Sabine Zeller, MSc, Claudio Rhyner, PhD, Norbert Meyer, MD, Peter.
Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric.

Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric.
Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois  Bruce K. Tan, MD, MS, Aiko I. Klingler, PhD,

Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois  Bruce K. Tan, MD, MS, Aiko I. Klingler, PhD,
Homozygous C1 inhibitor deficiency: The conclusion of a long search

Homozygous C1 inhibitor deficiency: The conclusion of a long search
Proprotein convertases generate a highly functional heterodimeric form of thymic stromal lymphopoietin in humans  Julie A. Poposki, MS, Aiko I. Klingler,

Proprotein convertases generate a highly functional heterodimeric form of thymic stromal lymphopoietin in humans  Julie A. Poposki, MS, Aiko I. Klingler,
Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps  Bruce K. Tan, MD, Quan-Zhen Li, PhD, Lydia.

Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps  Bruce K. Tan, MD, Quan-Zhen Li, PhD, Lydia.
IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis  Hyun-Woo Shin, MD, PhD, Dong-Kyu Kim, MD, Min-Hyun Park, MD,

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis  Hyun-Woo Shin, MD, PhD, Dong-Kyu Kim, MD, Min-Hyun Park, MD,
Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B

Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B
Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation 

Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation 
Frank Kirstein, PhD, Natalie E

Frank Kirstein, PhD, Natalie E
Is 9 more than 2 also in allergic airway inflammation?

Is 9 more than 2 also in allergic airway inflammation?
Activation of the ficolin-lectin pathway during attacks of hereditary angioedema  Dorottya Csuka, PhD, Lea Munthe-Fog, PhD, Estrid Hein, MSc, Zsuzsanna.

Activation of the ficolin-lectin pathway during attacks of hereditary angioedema  Dorottya Csuka, PhD, Lea Munthe-Fog, PhD, Estrid Hein, MSc, Zsuzsanna.

Similar presentations

Ads by Google