Association between dupilumab treatment effect on nasal polyp score and biomarkers of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyps in the phase 3 SINUS‐24 and SINUS‐52 trials

Airway inflammation plays a key role in asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The inflammatory process can vary in intensity thus affecting the clinical picture of the disease and, most importantly, the effectiveness of therapy. Today, there is still a high rate of growth in the incidence of asthma and CRSwNP and dissatisfaction with the effectiveness of existing therapy for severe forms of asthma, especially when asthma is associated with CRSwNP, so the main task is to find new approaches to diagnosis and therapy. The development of biologics is a promising step forward in achieving control of severe and poorly controlled asthma and recurrent CRSwNP that target individual and specific components of inflammation. One of the latest monoclonal antibodies is Dupilumab that has shown significant success in the treatment of asthma and CRSwNP. Dupilumab is a fully human monoclonal antibody directed against the -subunit of the Il-4 interleukin receptor (IL-4R), common to both IL-4 and IL-4/IL-13 receptor complexes. This contributes to the suppression of type 2 cytokine signaling (IL-4 and IL-13), since the IL-4/IL-13/STAT6 signaling pathway plays a crucial role in type 2-inflammation. Currently, Dupilumab is approved for the treatment of severe asthma and CRSwNP, so this article summarizes the main information about Dupilumab and its effectiveness in these diseases, as well as presents the results of clinical observation.

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Type 2 inflammation in chronic rhinosinusitis without nasal polyps: Another relevant endotype

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2020.04.040 ◽

2020 ◽

Vol 146 (2) ◽

pp. 337-343.e6

Author(s):

Tim Delemarre ◽

Gabriele Holtappels ◽

Natalie De Ruyck ◽

Nan Zhang ◽

Hans Nauwynck ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Type 2 Inflammation

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Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps

Mucosal Immunology ◽

10.1038/s41385-019-0215-8 ◽

2019 ◽

Vol 13 (1) ◽

pp. 86-95 ◽

Cited By ~ 5

Author(s):

Noriko Ogasawara ◽

Julie A. Poposki ◽

Aiko I. Klingler ◽

Bruce K. Tan ◽

Kathryn E. Hulse ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Type 2 Inflammation

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Type 2 inflammation-related comorbidities among patients with asthma, chronic rhinosinusitis with nasal polyps, and atopic dermatitis

10.1183/13993003.congress-2020.232 ◽

2020 ◽

Author(s):

Asif Khan ◽

Imène Gouia ◽

Siddhesh Kamat ◽

Benjamin Ortiz ◽

Robert Johnson ◽

...

Keyword(s):

Atopic Dermatitis ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Type 2 Inflammation

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Chronic rhinosinusitis with nasal polyposis (CRSwNP): the correlation between expression of Galectin-10 and Clinical-Cytological Grading (CCG)

American Journal of Rhinology and Allergy ◽

10.1177/19458924211049867 ◽

2021 ◽

pp. 194589242110498

Author(s):

Matteo Gelardi ◽

Giuseppe Stefano Netti ◽

Rossana Giancaspro ◽

Federica Spadaccino ◽

Antonio Pennella ◽

...

Keyword(s):

Mast Cells ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Nasal Polyposis ◽

Inflammatory Cells ◽

Eosinophilic Inflammation ◽

Double Positive ◽

Double Label ◽

Type 2 Inflammation

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is typically characterized by Type 2 inflammation. Several biomarkers of eosinophilic inflammation, including Galectin-10, also known as Charcot-Leyden crystal protein (CLCP), have been identified to establish eosinophilic infiltration of polyps, a reliable predictor of recurrence. Objective: We aimed to evaluate the Galectin-10 expression in nasal polyps of patients with CRSwNP and to assess the correlation of Charcot-Leyden crystals expression to the severity of CRSwNP according to Clinical-Cytological Grading (CCG). Methods A double-label immunofluorescence was performed to evaluate the expression of Gal-10, CD15, Tryptase, and CD63 and their eventual co-localization on histological samples of 18 patients with CRSwNP. Double-positive Gal-10+CD15+ and Galectin-10+Tryptase+ inflammatory cells were counted by confocal microscopy. Results Galectin-10 was detectable in all examined tissues from CRSwNP patients, and its expression increased as low, medium and high CCG tissues were examined, respectively. Galectin-10 was extensively present in inflammatory cells, while limited Galectin-10 deposits were detected around mucosal epithelial cells. Conclusion We showed the strong correlation between CCG and Galectin-10 expression, mainly colocalized with infiltrating eosinophils and mast-cells, in patients affected by CRSwNP.

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Type 2 inflammation suppression by T-regulatory cells attenuates the eosinophil recruitment in mucosa of chronic sinusitis

Clinical Science ◽

10.1042/cs20190388 ◽

2020 ◽

Vol 134 (2) ◽

pp. 123-138 ◽

Cited By ~ 2

Author(s):

Lihong Chang ◽

Zhiyuan Wang ◽

Shuaixiang Li ◽

Xiaohong Chen ◽

Xia Li ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Peripheral Blood ◽

Nasal Polyps ◽

Chronic Sinusitis ◽

Treg Cells ◽

Eosinophilic Infiltration ◽

Eosinophil Recruitment ◽

Pathologic Features ◽

Type 2 Inflammation

Abstract Type 2 inflammation and eosinophilic infiltration are prominent pathologic features of chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of the present study was to determine the roles of Tregs in controlling type 2 inflammation and inhibiting eosinophilic infiltration in CRSwNP. A total of 134 nasal polyps, 67 ostiomeatal complex from chronic rhinosinusitis (CRS) and 62 normal nasal tissues from controls were collected to study the enumeration and function of Tregs cells and the expressions of cytokine profiles via immunofluorescence staining, flow cytometry, qRT-PCR, ELISA, and/or H&E staining. The effects of Tregs on type2 and type3 inflammations were determined in an eosinophilic chronic sinusitis (ECRS) mice model. It was confirmed that the CRSwNP displayed the features of Th2 and Th17 cells-mediated inflammation, accompanying by an increased level of eosinophilic infiltration and the eosinophil cationic protein (ECP), with a decreased frequency of Treg cells. Furthermore, the percentages of CD4+CD25+CD127lowTreg and CD4+CD25+Foxp3+Treg were only decreased in the polyps of CRSwNP but not in the paired peripheral blood. The CRSwNP possessed the decreased Nrp1+Tregs, Helios+Treg, and low TGF-β and interleukin (IL)-10 expressions in Tregs. The ECRS mice showed similar inflammatory characteristics to CRSwNP patients. The adoptive transfer of CD4+CD25+Foxp3+ Treg cells significantly decreased the inflammatory cytokines, eosinophilic chemotactic factors in the mucosa of the ECRS mice without alteration of the immune balance in the peripheral blood and spleen. In conclusion, CRSwNP showed high type 2 and type3 inflammation and defective Tregs. The induced regulatory T cell (iTreg) may correct the imbalance between immune tolerance and effect via limiting the eosinophil recruitment of mucosa in CRSwNP.

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