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 ◽  
...  

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.

Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.


2016 ◽  
Vol 7 (1) ◽  
pp. ar.2016.7.0149 ◽  
Author(s):  
Namjil N. Tsybikov ◽  
Elena V. Egorova ◽  
Boris I. Kuznik ◽  
Elena V. Fefelova ◽  
Eli Magen

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.


2020 ◽  
Vol 63 (12) ◽  
pp. 579-585
Author(s):  
Do Hyun Kim ◽  
Boo-Young Kim ◽  
Il Hwan Lee ◽  
Sung Won Kim ◽  
Soo Whan Kim

Background and Objectives We evaluated differences in the pathophysiology of atopic and non-atopic eosinophilic nasal polyps and investigated their distinct inflammatory profiles.Subjects and Method A total of 36 patients were recruited: 10 controls (Group C), 14 with chronic rhinosinusitis with eosinophilic nasal polyps with atopy (Group A), and 12 without atopy (Group NA).Results Serum eosinophil counts, total immunoglobulin E, eosinophil cationic protein levels, and tissue eosinophil counts were elevated in Groups A and NA vs. Group C. Real-time polymerase chain reaction results showed increased GATA-3, interleukin (IL)-4, IL-33 levels, but decreased levels of retinoic acid-related orphan receptor gamma t, IL-17 in Groups A and NA. Related to the regulatory T (T-reg) cell response, forkhead box P3 (Foxp3<sup>+</sup>) (A: <i>p</i><0.001, NA: <i>p</i><0.001) and IL-10 (A: <i>p</i><0.001, NA: <i>p</i><0.001) levels were elevated and transforming growth factor-β levels (A: <i>p</i><0.001, NA: <i>p</i><0.001) were decreased in Group A and Group NA in comparison to those in Group C. The Foxp3<sup>+</sup> (<i>p</i>=0.001) and IL-10 (<i>p</i><0.001) were significantly higher in Group A than in Group NA.Conclusion T-reg cells and IL-10 may be major factors differentiating the pathophysiology of atopic and non-atopic eosinophilic nasal polyps, and the T helper (Th) 2/Th17/T-reg imbalance might be important in the development of eosinophilic nasal polyposis.


2021 ◽  
pp. 194589242110498
Author(s):  
Matteo Gelardi ◽  
Giuseppe Stefano Netti ◽  
Rossana Giancaspro ◽  
Federica Spadaccino ◽  
Antonio Pennella ◽  
...  

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.


2021 ◽  
pp. 000348942199503
Author(s):  
Michael A. Belsky ◽  
Erica Corredera ◽  
Hridesh Banerjee ◽  
John Moore ◽  
Li Wang ◽  
...  

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.


2021 ◽  
Vol 70 (2) ◽  
pp. 109-114
Author(s):  
Zuzana Balatková ◽  
Zdeněk Knížek ◽  
Jan Vodička ◽  
Jan Plzák

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


2020 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Y. Ohki ◽  
Y. Okamoto ◽  
T. Iinuma ◽  
H. Yamamoto ◽  
T. Toyotome ◽  
...  

2017 ◽  
Vol 131 (8) ◽  
pp. 707-713 ◽  
Author(s):  
K-J Cheng ◽  
Y-Y Xu ◽  
M-L Zhou ◽  
S-H Zhou ◽  
S-Q Wang

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.


OTO Open ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 2473974X1987507
Author(s):  
Ashley Lonergan ◽  
Theoharis Theoharides ◽  
Eirini Tsilioni ◽  
Elie Rebeiz

This pilot study was undertaken to isolate and quantify substance P (SP) and hemokinin 1 (HK-1) in the nasal lavage fluid of patients with chronic rhinosinusitis with nasal polyps to better elucidate the pathophysiology underlying this inflammatory process, which remains poorly understood. Mucus samples were collected from this introductory cohort of 10 patients diagnosed with chronic rhinosinusitis with nasal polyps at Tufts Medical Center (Boston, Massachusetts). Relative levels of SP and HK-1 were measured with enzyme-linked immunosorbent assay methods. Both inflammatory neuropeptides were found in detectable and comparable amounts in patient samples and in concentrations up to 100-fold those established in past literature. The presence of SP and HK-1 necessitates further investigation into their role in nasal polyposis and the potentiation of the chronic inflammation inherent to chronic rhinosinusitis. Downregulating these peptides could therefore provide novel treatment targets to manage this disease process.


2019 ◽  
Vol 139 (1) ◽  
pp. 48-51 ◽  
Author(s):  
Giuseppe Brescia ◽  
Paolo Sfriso ◽  
Gino Marioni

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