Characterization of immunoglobulin E plasma cells that are elevated in the upper airway mucosa of nonatopic patients with chronic rhinosinusitis without nasal polyps

AbstractEpithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of chronic rhinosinusitis (CRS). However, data of their distribution in upper airway mucosa are sparse. We aimed to provide quantitative, purely informative data on the distribution of these cell lineages and their coexpression patterns, which might help identifying, e.g., cells in the epithelium undergoing through epithelial–mesenchymal transition (EMT). For this purpose, we used immunofluorescence multichannel image cytometry (IMIC). We examined fixed paraffin-embedded tissue samples (FFPE) of six patients with chronic rhinosinusitis (CRS) and of three patients without CRS (controls). The direct-conjugated antibodies pancytokeratin, vimentin and CD45/CD18 were used for coexpression analysis in epithelial layer and lamina propria. Image acquisition and analysis were performed with TissueFAXS and StrataQuest, respectively. To distinguish positive from negative expression, a ratio between cell-specific immunostaining intensity and background was developed. Isotype controls were used as negative controls. Per patient, a 4.5-mm2 tissue area was scanned and a median of 14,875 cells was recognized. The most common cell types were cytokeratin-single-positive (26%), vimentin-single-positive (13%) and CD45/CD18-single-positive with CD45/CD18–vimentin-double-positive cells (29%). In the patients with CRS, CD45/CD18-single-positive cells were 3–6 times higher compared to the control patients. In the epithelial layer, cytokeratin–vimentin-double-positive EMT cells were observed 3–5 times higher in the patients with CRS than in the control patients. This study provided quantitative data for the distribution of crucial cell types in CRS. Future studies may focus on the distribution and coexpression patterns of different immune cells in CRS or even cancer tissue.

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Biological therapy of chronic rhinosinusitis

Otorinolaryngologie a foniatrie ◽

10.48095/ccorl2021109 ◽

2021 ◽

Vol 70 (2) ◽

pp. 109-114

Author(s):

Zuzana Balatková ◽

Zdeněk Knížek ◽

Jan Vodička ◽

Jan Plzák

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Biological Therapy ◽

Immunoglobulin E ◽

Sinus Surgery ◽

Therapeutic Choice ◽

First Choice ◽

Intranasal Steroids

The aim of this paper is to present an up-to-date information about therapeutical options in chronic rhinosinusitis with nasal polyps. First choice therapy is a long term regular application of intranasal steroids in combination with salinic solution douches. If this treatment is not eff ective enough, then the pulses of systemic steroids are indicated. If the sufficient control of the disease is not achieved, then surgery is a therapeutic choice; it means functional endoscopic sinus surgery in the extent corresponding to the extension of the sinus disease. However, there remains a certain group of patients in whom the results with this treatment are not optimal. The type 2 immunopathological response affects relevantly the course of the disease. Nowadays, the research is done in this field. Specific agents, which are able to block circulating inflammatory mediators or bind receptors for these mediators are developed and studied. The results of the studies having been completed by now are promising. Keywords: biological therapy – chronic rhinosinusitis – nasal polyps – dupilumab – immunoglobulin E – interleukin

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Local fungus-specific Immunoglobulin E production in chronic rhinosinusitis with nasal polyps

Rhinology Journal ◽

10.4193/rhin18.225 ◽

2020 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Y. Ohki ◽

Y. Okamoto ◽

T. Iinuma ◽

H. Yamamoto ◽

T. Toyotome ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Immunoglobulin E ◽

Specific Immunoglobulin E ◽

Specific Immunoglobulin

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Role of local allergic inflammation and Staphylococcus aureus enterotoxins in Chinese patients with chronic rhinosinusitis with nasal polyps

The Journal of Laryngology & Otology ◽

10.1017/s0022215117001335 ◽

2017 ◽

Vol 131 (8) ◽

pp. 707-713 ◽

Cited By ~ 5

Author(s):

K-J Cheng ◽

Y-Y Xu ◽

M-L Zhou ◽

S-H Zhou ◽

S-Q Wang

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Immunoglobulin E ◽

Allergic Inflammation ◽

Staphylococcal Enterotoxin ◽

Eosinophilic Chronic Rhinosinusitis ◽

Specific Immunoglobulin E ◽

Specific Immunoglobulin ◽

Local Allergy

AbstractObjective:To investigate the role of local allergic inflammation and Staphylococcus aureus enterotoxins in chronic rhinosinusitis with nasal polyps.Methods:This study included 36 patients with chronic rhinosinusitis with nasal polyps and 18 controls. Total immunoglobulin E, eosinophil cationic protein, staphylococcal enterotoxin types A and B specific immunoglobulin E, staphylococcal enterotoxin types A and B, and myeloperoxidase levels were determined.Results:Four patients with chronic rhinosinusitis with nasal polyps had a local allergy. All chronic rhinosinusitis with nasal polyps patients tested negative for staphylococcal enterotoxin types A and B specific immunoglobulin E. The chronic rhinosinusitis with nasal polyps group had significantly elevated staphylococcal enterotoxin types A and B levels in the supernatant. Fourteen patients belonged to the eosinophilic chronic rhinosinusitis with nasal polyps group and the others were characterised as having non-eosinophilic chronic rhinosinusitis with nasal polyps.Conclusion:Local allergy may play a role in chronic rhinosinusitis with nasal polyps, independent of staphylococcal enterotoxin superantigens. Staphylococcal enterotoxins may be important in the pathogenesis of chronic rhinosinusitis with nasal polyps; however, their roles as superantigens were not confirmed in this study. In Chinese subjects, chronic rhinosinusitis with nasal polyps usually manifests as a neutrophilic inflammation.

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Heat Shock Protein 70 and Anti-heat Shock Protein 70 Antibodies in Nasal Secretions of Patients with Chronic Rhinosinusitis

Allergy & Rhinology ◽

10.2500/ar.2016.7.0149 ◽

2016 ◽

Vol 7 (1) ◽

pp. ar.2016.7.0149 ◽

Cited By ~ 2

Author(s):

Namjil N. Tsybikov ◽

Elena V. Egorova ◽

Boris I. Kuznik ◽

Elena V. Fefelova ◽

Eli Magen

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Chronic Rhinosinusitis ◽

Heat Shock Protein 70 ◽

Nasal Polyps ◽

Immunoglobulin E ◽

Clinical Severity ◽

Secretory Iga ◽

Enzyme Linked Immunosorbent Assay ◽

Antibody Levels

Background The issue of heat shock protein (HSP) 70 and anti-HSP70 antibodies in chronic rhinosinusitis (CRS) has never been explored. Objective To determine the nasal secretion (NS) levels of HSP70 and anti-HSP70 antibodies in patients with CRS with nasal polyps (CRSwNP) and patients with CRS without nasal polyps (CRSsNP), and to evaluate their associations with CRS clinical severity and correlation with NS interleukin (IL), IL-5 and interferon λ. Methods CRS severity was determined by Lund-Mackay scores. Levels of immunoglobulin E (IgE), IL-4, IL-5, interferon A, HSP70, and anti-HSP70 antibody levels in NS were measured by enzyme-linked immunosorbent assay. Results Forty-six patients with CRSsNP (25 women [543%] and 21 men [45.7%], mean [standard deviation {SD}]) age, 34.1 ± 123 years; 54 patients with CRSwNP (24 women [44.4%] and 30 men [55.6%], mean [SD] age, 37.9 ± 17.5 years). A group of 40 healthy subjects served as controls. Compared with the controls (with a mean [SD] NS HSP70 level of 0.05 ± 0.03 μg/mL), mean [SD]NS HSP70 levels in both the CRSsNP group (0.16 ± 0.07 ixg/mL) and CRSwNP group (0.21 ± 0.10 μg/mL) were increased (p < 0.001). Similarly, the mean (SD) NS anti-HSP70 antibody levels were significantly higher in patients with CRSwNP (0.25 ± 0.09 optical density value [ODV]) compared with CRSsNP (0.13 ± 0.04 ODV) (p < 0.001) and healthy controls (0.14 ± 0.02 ODV) (p < 0.001). NS HSP70 in subjects with CRSwNP showed a significant positive correlation with the Lund-Mackay score (r = 0.31; p < 0.05). NS levels of either HSP70 or anti-HSP70 antibodies were strongly correlated with NS IL-4 in the CRSwNP group (r = 0.62, p < 0.001; and r = 0.69, p < 0.001, respectively). Conclusion NS concentrations of HSP70 and secretory IgA anti HSP70 antibodies are increased in CRSwNP (but not in CRSsNP) and correlate positively with the Lund-Mackay score, NS IL-4, and NS IL-5.

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Biofilms and inflammation in patients with chronic rhinosinusitis

Medicine and Pharmacy Reports ◽

10.15386/mpr-1691 ◽

2020 ◽

Author(s):

Lavinia-Gianina Manciula ◽

Ionut Isaia Jeican ◽

Lucian Barbu Tudoran ◽

Silviu Albu

Keyword(s):

Chronic Rhinosinusitis ◽

Plasma Cell ◽

Nasal Polyps ◽

Nasal Polyposis ◽

Inflammatory Cell ◽

Plasma Cells ◽

Strongly Correlated ◽

Cell Counts ◽

Deviated Septum ◽

Nasal Pathology

Introduction. The aim of the present study is to evaluate the presence of biofilms in patients with chronic rhinosinusitis (CRS), with or without nasal polyps, and their relationship to eosinophils and plasma cells. We compared the results with those obtained in nonCRS patients. Methods. A total of 50 patients were included in the study, 30 CRSwNP patients, 10 CRSsNP cases and 10 control patients who were operated for deviated septum. Biofilm detection was performed by means of H&E staining and SEM. Eosinophil and plasma cell values were recorded and compared between groups. Results. Biofilms were identified in 30 patients (60%), 76.6% (23 out of 30) of the CRSwNP patients, 70% (7 out of 10) of the CRSsNP patients and none of the septoplasty patients. Eosinophil and plasma cell values were more elevated in CRS patients, being strongly correlated to biofilm presence and nasal polyposis. Conclusion. Biofilm presence was demonstrated in many of the CRS patients, with no evidence in the control cases. Our study findings indicate that inflammatory cell counts are higher in patients with CRS compared to controls, but also more elevated in patients with polyposis. In biofilm-positive patients, eosinophil and plasma cell counts were greater than those in patients without biofilms, demonstrating the proinflammatory action of the biofilm in the sino-nasal pathology.

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Predictive and Diagnostic Value of Nasal Nitric Oxide in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

International Archives of Allergy and Immunology ◽

10.1159/000509211 ◽

2020 ◽

Vol 181 (11) ◽

pp. 853-861

Author(s):

Hao Lv ◽

Pei-Qiang Liu ◽

Rong Xiang ◽

Wei Zhang ◽

Shi-Ming Chen ◽

...

Keyword(s):

Nitric Oxide ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Upper Airway ◽

Central China ◽

Clinical Parameters ◽

Total Ige ◽

Nasal Nitric Oxide ◽

Eosinophilic Chronic Rhinosinusitis ◽

Plasma Cytokines

Background: A hallmark of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is mucosal eosinophil-predominant inflammation. Nasal nitric oxide (nNO) is a known biomarker of eosinophilic inflammation in the upper airway. However, the utility of nNO measurement in the upper airway remains controversial. The present study aimed to compare the use of other clinical parameters with nNO to prediagnose patients with eCRSwNP from Central China. Methods: From June 2019 to December 2019, 70 patients with CRSwNP undergoing endoscopic sinus surgery and 30 healthy subjects were enrolled. nNO measurements were performed in all of these subjects. Computed tomography scans, full blood count with differential analysis, and determination of total immunoglobulin E (total IgE) and plasma cytokines were performed before surgery. Receiver operating characteristic curves and logistic regression analysis were used to assess the predictive potential of the clinical parameters. Results: We recruited 24 patients with eCRSwNP and 46 with noneosinophilic CRSwNP (non-eCRSwNP). In patients with eCRSwNP, nNO levels were significantly higher than those in patients with non-eCRSwNP (p < 0.0001). Blood eosinophil percentages and counts, total IgE, and CT-derived ethmoid sinus and maxillary sinus ratio (E/M ratio) were all significantly higher compared with those in patients with non-eCRSwNP (p < 0.05). To diagnose eCRSwNP, the highest area under the curve (0.803) was determined for nNO. At a cutoff of >329 parts per billion (ppb), the sensitivity was 83.30% and the specificity was 71.70%. However, the levels of plasma cytokines Th1/Th2 were not significantly different between the histological types of CRSwNP (p > 0.05). Conclusion: Measurement of nNO is useful for the early diagnosis of eCRSwNP.

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Recent advances in understanding chronic rhinosinusitis endotypes

F1000Research ◽

10.12688/f1000research.16222.1 ◽

2018 ◽

Vol 7 ◽

pp. 1909 ◽

Cited By ~ 5

Author(s):

Eric F. Succar ◽

Justin H. Turner

Keyword(s):

Disease Management ◽

Chronic Rhinosinusitis ◽

Inflammatory Disease ◽

Nasal Polyps ◽

Molecular Biomarkers ◽

Treatment Algorithms ◽

Therapeutic Implications ◽

Personalized Approach

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with an as-yet-undefined etiology. The management of CRS has historically been phenotypically driven, and the presence or absence of nasal polyps has frequently guided diagnosis, prognosis, and treatment algorithms. Research over the last decade has begun to question the role of this distinction in disease management, and renewed attention has been placed on molecular and cellular endotyping and a more personalized approach to care. Current research exploring immunologic mechanisms, inflammatory endotypes, and molecular biomarkers has the potential to more effectively delineate distinct and clinically relevant subgroups of CRS. The focus of this review will be to discuss and summarize the endotypic characterization of CRS and the potential diagnostic and therapeutic implications of this approach to disease management.

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Innate lymphoid cells in the upper airways: importance of CD117 and IL-1RI expression

European Respiratory Journal ◽

10.1183/13993003.00742-2018 ◽

2018 ◽

Vol 52 (6) ◽

pp. 1800742 ◽

Cited By ~ 5

Author(s):

Koen Van Crombruggen ◽

Sylvie Taveirne ◽

Gabriele Holtappels ◽

Georges Leclercq ◽

Claus Bachert

Keyword(s):

Nasal Polyps ◽

Upper Airway ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Type I ◽

Upper Airways ◽

Airway Mucosa

Although type 1, 2 and 3 innate lymphoid cells (ILC1s, ILC2s and ILC3s, respectively) are emerging as important cell populations regulating tissue homeostasis, remodelling and inflammation, a vast majority of our knowledge stems from in vitro and murine experiments, and requires thorough confirmation in human diseases.Relative levels of ILCs were evaluated by means of flow cytometry in freshly resected human upper airways mucosa of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP), taking into account the patient's clinical parameters and disease comorbidities.We report that the CD117 and interleukin-receptor type I (IL-1RI) expression status of human ILC2s depends on the local tissue environment. Only CD117+ IL-1RI+ ILC2s, exclusively present in CRSwNP, possess an interrelationship with type 2 T-helper cell cytokine and eosinophil levels in human upper airway mucosa. In CRSsNP, mainly CD117−IL-1RI− ILC2s are increased, yielding lower eosinophilia in this disease despite the high levels of ILC2s.These data unveil that the CD117− and CD117+ fractions within the native human ILC2 population are not a random phenomenon, in contrast to what could be concluded from in vitro data, and that the IL-1RI expression is not ubiquitous in ILC2s in vivo in humans, which cannot be assessed via in vitro and murine experiments.

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Cellular phenotyping of chronic rhinosinusitis with nasal polyps

Rhinology Journal ◽

10.4193/rhino15.271 ◽

2016 ◽

Vol 54 (2) ◽

pp. 150-159

Author(s):

Hongfei Lou ◽

Yifan Meng ◽

Yingshi Piao ◽

Nan Zhang ◽

Claus Bachert ◽

...

Keyword(s):

Cluster Analysis ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Plasma Cells ◽

Inflammatory Cells ◽

Recurrence Rates ◽

Tissue Eosinophilia ◽

Inflammatory Pattern ◽

Polyp Recurrence ◽

Cellular Phenotypes

Background: Defining the phenotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) with prognosis may lead to delivery of personalized treatment. This study aimed to identify cellular phenotypes of CRSwNP using cluster analysis and define an algorithm for different clusters associated with polyp recurrence. Methods: Overall, 366 patients with CRSwNP were enrolled in this retrospective analysis. Eighteen variables, including clinical characteristics and tissue/peripheral inflammatory cells assessments, were selected for factor analysis. Unsupervised cluster analysis was performed after variables reduction and standardization and differences in polyp recurrence during follow-up for a minimum of 24 months were analysed among clusters. Discriminant analysis was further used to develop a clinically useful algorithm for predicting clustering. Results: Five phenotypic clusters were identified. Clusters 1 and 2 were plasma cell-dominant and lymphocyte-dominant phenotypes, respectively. Cluster 3 revealed a mixed inflammatory pattern. Cluster 4 was characterized by infiltration of predominantly neutrophils. Cluster 5 was characterized by a marked tissue eosinophilia and highest recurrence rate of 98.5%. The clinical algorithm predicted clustering with 93.7% accuracy. Conclusions: Chinese CRSwNP patients may be classified into five phenotypes with different polyp recurrence rates, based on the presence of predominantly plasma cells, lymphocytes, neutrophils, eosinophils or mixed inflammatory cells in polyps.

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