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

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.

P505 DUPILUMAB EFFECT ON TYPE 2 INFLAMMATION BIOMARKERS IN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS AND NSAID-ERD

2020 ◽  
Vol 125 (5) ◽  
pp. S48
Author(s):  
A. White ◽  
S. Fujieda ◽  
T. Takabayashi ◽  
N. Daizadeh ◽  
Y. Deniz ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Type 2 Inflammation

scholarly journals Dupilumab: new opportunities for the treatment of asthma and chronic rhinosinusitis with nasal polyps

2021 ◽  
Vol 18 (1) ◽  
pp. 18-31
Author(s):  
Miramgul E. Dyneva ◽  
Gulyumkhan E. Aminova ◽  
Oksana Kurbacheva ◽  
Natalya I. Il'ina
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Human Monoclonal Antibody ◽  
High Rate ◽  
Cytokine Signaling ◽  
Main Task ◽  
Receptor Complexes ◽  
Target Individual ◽  
Type 2 Inflammation

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.

scholarly journals Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis

2019 ◽  
Vol 20 (21) ◽  
pp. 5461 ◽  
Author(s):  
Martina Mihalj ◽  
Maro Bujak ◽  
Josip Butković ◽  
Željko Zubčić ◽  
Maja Tolušić Levak ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Target Gene ◽  
Nasal Polyposis ◽  
Sinus Surgery ◽  
Mrna Levels ◽  
Nasal Turbinate ◽  
Family Factor ◽  
Nasal Septoplasty ◽  
Type 2 Inflammation

Trefoil family factor (TFF) proteins contribute to antimicrobial defense and the maintenance of sinonasal epithelial barrier integrity. Dysregulation of TFF expression may be involved in the development of chronic inflammation and tissue remodeling characteristically found in chronic rhinosinusitis with nasal polyposis (CRSwNP). Expressions of TFF1 and TFF3 were determined in specimens of middle nasal turbinate (MNT-0), bulla ethmoidalis (BE), and nasal polyps (NP) from CRSwNP patients (n = 29) and inferior nasal turbinate from a group of control patients (underwent nasal septoplasty, n = 25). An additional MNT sample was collected 6 months after functional endoscopic sinus surgery (FESS, MNT-6). TFF1 mRNA levels were significantly reduced in all specimens by approximately three- to five-fold, while TFF3 was increased in MNT-0, as compared with controls. Six months after surgery their levels were reversed to control values. CRSwNP patients with S. epidermidis isolated from sinus swabs showed upregulation of TFF3 in MNT and NP as compared with patients with sterile swabs. Target gene regulation was not affected by the presence of type 2 inflammation in patients with confirmed allergy. Results of this study imply participation of TFFs genes in the development of CRSwNP.

scholarly journals Immunopathology Features of Chronic Rhinosinusitis in High-altitude Dwelling Tibetans

2013 ◽  
Vol 4 (2) ◽  
pp. ar.2013.4.0055 ◽  
Author(s):  
Ba Luo ◽  
Liu Feng ◽  
Du Jintao ◽  
Liu Yafeng ◽  
Liu Shixi ◽  
...  
Keyword(s):  
Mast Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Transforming Growth Factor ◽  
Immunoglobulin E ◽  
Eosinophil Cationic Protein ◽  
Inflammatory Cells ◽  
Cold Weather ◽  
Enzyme Linked Immunosorbent Assay ◽  
Treg Function

Chronic rhinosinusitis (CRS) presents distinct inflammatory and remodeling patterns in different populations and environments. Tibetan ethnic groups live at high altitudes and in cold weather conditions. We sought to examine whether Tibetans exhibit distinct CRS pathology or characteristics. Sinonasal polyps and mucosal tissue were obtained from 14 Tibetan patients with CRS and nasal polyps (CRSwNPs), 13 patients with CRS without nasal polyps (CRSsNPs), and 12 Tibetan controls. Tissue homogenates and serum samples were assayed for several T-helper (TH) cell cytokines and mediators using enzyme linked immunosorbent assay profiles were measured using quantity polymerase chain reaction. Several key inflammatory cells were examined for immunohistochemical markers. CRSwNPs were characterized by increased mediator promoting eosinophilic inflammation (interleukin [IL]-5, eosinophil cationic protein, and total immunoglobulin E) and slight synergism with expression of IL-8, IL-2sRa, IL-1beta, IL-6, and myeloperoxidase, and a predominance of eosinophils, mast cells, and neutrophils. GATA-3 transcription factor was significantly increased and Foxp3 showed a tendency to be impaired in CRSwNPs compared with controls. CRSsNPs were characterized by significantly high levels of transforming growth factor beta1, increased interferon γ, and a significant enhancement of Foxp3 and T-beta compared with CRSwNPs. There were reduced numbers of inflammatory cells but increased levels of macrophages in CRSsNPs. Compared with CRSsNPs, CRSwNPs present a severe inflammatory reaction and show a TH2 milieu with apparently impaired regulatory T cells (Treg) function and increased inflammatory cells infiltration predominated by eosinophilic and mast cells. In contrast, TH1 polarization with enhanced Treg function and increased levels of macrophages appear in CRSsNPs.

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

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

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

2019 ◽  
Vol 13 (1) ◽  
pp. 86-95 ◽  
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

scholarly journals Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation

2021 ◽  
Vol 6 (56) ◽  
pp. eabb7221
Author(s):  
Daniel F. Dwyer ◽  
Jose Ordovas-Montanes ◽  
Samuel J. Allon ◽  
Kathleen M. Buchheit ◽  
Marko Vukovic ◽  
...  
Keyword(s):  
Mast Cells ◽  
Nasal Polyposis ◽  
Inflammatory Diseases ◽  
Severe Disease ◽  
Intermediate Phenotype ◽  
Airway Mucosa ◽  
Fibrotic Diseases ◽  
Type 2 Inflammation

Mast cells (MCs) play a pathobiologic role in type 2 (T2) allergic inflammatory diseases of the airway, including asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Distinct MC subsets infiltrate the airway mucosa in T2 disease, including subepithelial MCs expressing the proteases tryptase and chymase (MCTC) and epithelial MCs expressing tryptase without chymase (MCT). However, mechanisms underlying MC expansion and the transcriptional programs underlying their heterogeneity are poorly understood. Here, we use flow cytometry and single-cell RNA-sequencing (scRNA-seq) to conduct a comprehensive analysis of human MC hyperplasia in CRSwNP, a T2 cytokine–mediated inflammatory disease. We link discrete cell surface phenotypes to the distinct transcriptomes of CRSwNP MCT and MCTC, which represent polarized ends of a transcriptional gradient of nasal polyp MCs. We find a subepithelial population of CD38highCD117high MCs that is markedly expanded during T2 inflammation. These CD38highCD117high MCs exhibit an intermediate phenotype relative to the expanded MCT and MCTC subsets. CD38highCD117high MCs are distinct from circulating MC progenitors and are enriched for proliferation, which is markedly increased in CRSwNP patients with aspirin-exacerbated respiratory disease, a severe disease subset characterized by increased MC burden and elevated MC activation. We observe that MCs expressing a polyp MCT–like effector program are also found within the lung during fibrotic diseases and asthma, and further identify marked differences between MCTC in nasal polyps and skin. These results indicate that MCs display distinct inflammation-associated effector programs and suggest that in situ MC proliferation is a major component of MC hyperplasia in human T2 inflammation.

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

2020 ◽  
Vol 134 (2) ◽  
pp. 123-138 ◽  
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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