scholarly journals Immune Imbalance in Nasal Polyps of Caucasian Chronic Rhinosinusitis Patients Is Associated with a Downregulation of E-Selectin

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Michael Könnecke ◽  
Robert Böscke ◽  
Anja Waldmann ◽  
Karl-Ludwig Bruchhage ◽  
Robert Linke ◽  
...  

Chronic rhinosinusitis with nasal polyps (CRSwNP) in Caucasians is a chronic Th2 inflammatory disease of the nasal and paranasal mucosa and the recruitment of leukocytes to the site of inflammation is poorly understood. We studied mRNA and protein expression profiles of adhesion molecules in nasal polyp and associated inferior turbinate tissues using molecular, biochemical, and immunohistological methods. Analysis showed a strongly decreased E-selectin expression in nasal polyps with a significant difference between eosinophil and neutrophil counts in nasal polyps and balanced counts in inferior turbinates. E-selectin expression is known to be downregulated in a Th2 milieu and has an essential role in immunosurveillance by locally activating neutrophil arrest and migratory function. A downregulation of E-selectin may come along with an immune imbalance in Caucasian nasal polyps due to a significant inhibition of neutrophil recruitment. Therefore, we suggest that an upregulation of E-selectin and the associated influx of neutrophils may play a significant role in the resolution of inflammation as well as for the pathophysiology of nasal polyps of Caucasian chronic rhinosinusitis patients.

2018 ◽  
Author(s):  
Kristi Biswas ◽  
Raewyn Cavubati ◽  
Shan Gunaratna ◽  
Michael Hoggard ◽  
Sharon Waldvogel-Thurlow ◽  
...  

Chronic rhinosinusitis (CRS) is a heterogeneous condition characterised by persistent sinus inflammation and microbial dysbiosis. This study aimed to identify clinically relevant sub-groups of CRS patients based on distinct microbial signatures, with a comparison to the commonly used phenotypic subgrouping approach. The underlying drivers of these distinct microbial clusters were also investigated, together with associations with epithelial barrier integrity. Sinus biopsies were collected from CRS patients (n=23), and disease controls (n=8). Expression of 42 tight junction genes was evaluated using quantitative PCR, together with microbiota analysis and immunohistochemistry for measuring mucosal integrity and inflammation. CRS patients clustered into two distinct microbial sub-groups using probabilistic modelling Dirichlet (DC) multinomial mixtures. DC1 exhibited significantly reduced bacterial diversity, increased dispersion, and was dominated by Pseudomonas, Haemophilus, and Achromobacter. DC2 had significantly elevated B-cells, incidence of nasal polyps, and higher numbers of Anaerococcus, Megasphaera, Prevotella, Atopobium, and Propionibacterium. In addition, each DC exhibited distinct tight junction gene and protein expression profiles compared with controls. Stratifying CRS patients based on clinical phenotypic subtypes (absence or presence of nasal polyps (CRSsNP or CRSwNP respectively) or with cystic fibrosis (CRSwCF)) did account for a larger proportion of the variation in the microbial dataset compared with DC groupings. However, no significant differences between CRSsNP and CRSwNP cohorts were observed for inflammatory markers, beta-dispersion and alpha diversity measures. In conclusion, both stratification approaches used had benefits and pitfalls, but DC clustering did provide greater resolution when studying tight junction impairment. Future studies in CRS should give careful consideration into the patient subtyping approach used.


2015 ◽  
Vol 53 (4) ◽  
pp. 345-352
Author(s):  
Y.B. Zheng ◽  
Y. Zhao ◽  
L.Y. Yue ◽  
P. Lin ◽  
Y.F. Liu ◽  
...  

Background: DNA methylation has been implicated in the pathogenesis of allergy and atopy. This study aimed to identify whether DNA methylation also plays an important role in the pathogenesis of nasal polyps (NP). Methodology: NP tissues were obtained from 32 patients with chronic rhinosinusitis with bilateral NP. Biopsies of inferior turbinate mucosa (ITM) were taken from 18 patients who underwent rhinoseptoplasty (control group). The methylated genes, which were detected by DNA methylation microarray, were validated by methylation-specific polymerase chain reaction, bisulphite sequencing, real-time polymerase chain reaction and immunohistochemistry. Results: DNA methylation microarray identified 8,008 CpG islands in 2,848 genes. One hundred and ninety-eight genes were found to have a methylated signal in the promoter region in NP samples compared with ITM samples. The four top genes that changed, COL18A1, EP300, GNAS and SMURF1, were selected for further study. The methylation frequency of COL18A1 was significantly higher in NP samples than in ITM samples. Conclusions: DNA methylation might play an important role in the pathogenesis of NP. Promoter methylation of COL18A1 was found to be significantly increased in NP tissues, further studies are necessary to confirm the significance of these epigenetic factors in the mechanisms underlying the development or persistence of NP.


2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Jingyun Li ◽  
Jian Jiao ◽  
Yunbo Gao ◽  
Yuan Zhang ◽  
Luo Zhang

Abstract Background This study was performed to determine whether there was any association between abnormal DNA methylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS). Methods A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and 21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal resistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients and inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human nasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA methylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER. Results A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased methylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false discovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated with olfactory score (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) and unilateral nasal resistance at 75 Pa (r = 0.24, P = 0.04; r = 0.24, P = 0.036) and 150 Pa (r = 0.34, P = 0.004; r = 0.25, P = 0.031). Total nasal resistance at 75 Pa/150 Pa or serum total IgE levels were not correlated with the methylation ratios at either CpG unit. Conclusions Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis; however these findings need to be confirmed in larger multicentre group studies.


2019 ◽  
Vol 16 (2) ◽  
pp. 50-60 ◽  
Author(s):  
E L Savlevich ◽  
M E Dyneva ◽  
L E Gaganov ◽  
V I Egorov ◽  
A N Gerasimov ◽  
...  

Chronic rhinosinusitis with nasal polyps (CRSwNP) may vary in clinical manifestations and can often be associated with a number of comorbid diseases. For a practitioner it is important to forecast the development of the disease, evaluate the risk of relapse and select the most efficient method of treatment in each clinical case. At present, there are no standardized and validated diagnostic biomarkers that could be used as predictors of CRSwNP clinical course. Purpose of the study: to develop diagnostic and treatment algorithm for varies CRSwNP phenotypes based on clinical and laboratory parameters. Materials and methods, CRSwNP patients were split into 3 groups: group 1 - CRSwNP without allergy and asthma; group 2 - CRSwNP with allergic rhinitis and/or allergic asthma; group 3 - CRSwNP with non-allergic asthma. All patients were subjected to nasal cavity endoscopy and nasal polyps biopsy, allergological examination, histological analysis of polyp stroma to detect the leukocytes infiltration and eosinophil-neutrophil index (ENI). Results, CRSwNP phenotypes show significant difference in clinical manifestations of rhinosinusitis (p


2022 ◽  
Vol 20 ◽  
pp. 205873922110529
Author(s):  
Kota Takemoto ◽  
Sachio Takeno ◽  
Takashi Ishino ◽  
Tsutomu Ueda ◽  
Takao Hamamoto ◽  
...  

Introduction Nitric oxide (NO) is synthesized through NO synthase (NOS). The proximal NOS2 gene promoter contains the pentanucleotide CCTTT repeat polymorphism. We examined whether CCTTT repeats are associated with NOS2 expression in the sinonasal tissues and clinical manifestations in patients with chronic rhinosinusitis. Methods Mucosal specimens were obtained from the ethmoid sinus and inferior turbinate of 30 eosinophilic chronic rhinosinusitis (ECRS) and 28 non-ECRS patients. CCTTT repeats were classified into short alleles (S), with less than or equal to 14, and long alleles (L), with more than 14. The subjects were classified into the L/S + L/L and S/S groups. Results In ECRS, the NOS2 mRNA levels of the ethmoid sinus mucosa were significantly higher in the L/S + L/L group than in the S/S group (median, 1.66 and 0.77, respectively). On the ther hand, ECRS patients showed no significant difference in the NOS2 mRNA level of the inferior turbinate between the L/S + L/L group and the S/S group (median, 0.63 and 0.88, respectively). In ECRS, preoperative SNOT-22 were significantly higher in the L/S + L/L group than in the S/S group, whereas the former group showed a lower postoperative recurrence risk. Conclusion CCTTT repeat polymorphism in the NOS2 promotor gene may be a useful indicator to evaluate ECRS severity and prognosis.


2019 ◽  
Vol 33 (5) ◽  
pp. 478-482 ◽  
Author(s):  
Kristin A. Seiberling ◽  
Stephanie C. Kidd ◽  
Grace H. Kim ◽  
Christopher A. Church

Background Topical nasal steroids are commonly prescribed to patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) following endoscopic sinus surgery (ESS). They are found to be effective in improving symptoms and quality of life as well as reducing the incidence of nasal polyps recurrence. Objective We sought to determine whether a higher concentration of topical nasal steroid spray is more effective than the standard nasal steroid spray in controlling symptoms and preventing recurrence of polyps in patients with CRSwNP who underwent ESS. Method A double-blind randomized controlled trial was performed on patients with CRSwNP after ESS. Patients were randomized into 2 treatment groups: one received topical nasal dexamethasone 0.032% and the other, fluticasone proprionate. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy nasal endoscopy scores were measured at the initiation of topical nasal steroid treatment and then at approximately 4-, 8-, and 12-week intervals. Results Thirty-nine patients were enrolled in the study. Eighteen patients continued using the medications prescribed to them for the duration of the study. There were 8 patients in the dexamethasone group and 10 patients in the fluticasone group. Both groups saw significant improvements in postoperative SNOT-22 and Lund-Kenney scores over time. There was no significant difference in improvement between the groups. Conclusion There is no significant increased benefit in using a higher dose nasal steroid spray compared to the standard dose nasal steroid spray after ESS.


2015 ◽  
Vol 129 (9) ◽  
pp. 865-869 ◽  
Author(s):  
D G Ioannidis ◽  
V A Lachanas ◽  
Z Florou ◽  
J G Bizakis ◽  
E Petinaki ◽  
...  

AbstractIntroduction:The role played byMycoplasma pneumoniaeandChlamydophila pneumoniaein the pathogenesis of chronic rhinosinusitis with nasal polyps has been the object of ongoing debate. We used real-time polymerase chain reaction to investigate the prevalence of both microorganisms in the nasal tissue samples of patients and controls.Methods:We extracted DNA from nasal polyp samples obtained during functional endoscopic sinus surgery and the inferior turbinate samples of controls undergoing septoplasty. We used the highly sensitive real-time polymerase chain reaction to detect the presence ofM pneumoniaeandC pneumoniaeDNA.Results:Patients with chronic rhinosinusitis with nasal polyps consisted of 62 individuals (39 men; mean age 51 years); the control group consisted of 24 individuals (13 men; mean age 45 years). All samples from both groups were negative forM pneumoniaeandC pneumoniaeDNA.Conclusion:We have demonstrated that the likelihood ofM pneumoniaeandC pneumoniaeacting as an ongoing inflammatory stimulus in chronic rhinosinusitis with nasal polyps is slim.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Thaís Tibery Espir ◽  
Luanda de Paula Figueira ◽  
Maricleide de Farias Naiff ◽  
Allyson Guimarães da Costa ◽  
Marcelo Ramalho-Ortigão ◽  
...  

The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species ofLeishmaniain Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified asLeishmania guyanensis,L. naiffi, andL. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to theLeishmaniaspecies. Infection caused byL. guyanensisaccounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-γ, IL-4, and IL-17 when compared to infection byL. amazonensis. Patients with infection caused byL. naiffishowed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed.


2019 ◽  
Vol 7 (11) ◽  
pp. 1733-1738 ◽  
Author(s):  
Effy Huriyati ◽  
Eryati Darwin ◽  
Yanwirasti Yanwirasti ◽  
Irza Wahid

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging clinical entity with its propensity for recurrence. This disease decreases the patients’ quality of life and creates a high economic burden. An effort to investigate the aetiology of recurrent polyps have to be more alert. AIM: This study aims to prove the differences in expression of IL-5, IL-8, IL-17A and TGF-β1 in mucosal and polyp tissue between CRSwNP and recurrent CRSwNP and also to determine which expression of cytokines that have the main role in mucosal and polyp tissue in recurrent CRSwNP. MATERIAL AND METHODS: An observational study was conducted with a comparative cross-sectional design of CRS patients with 15 recurrent CRSwNP and CRSwNP who had never undergone surgery for as many as 15 polyps. Mucosal specimens of nasal polyps are taken by brushing, and polyp tissue specimens are taken during surgical removal of nasal polyps. Specimens from the polyp mucosa were examined by ELISA while the polyp tissue specimens were carried out immunohistochemistry (IHC). RESULTS: The result showed that there is a significant difference in IL-5 expression in the polyp mucosal between CRSwNP with recurrent CRSwNP, where expression is higher in recurrent CRSwNP. The expression of IL-8, IL-17 and TGF-β1 were lower in recurrent CRSwNP, but the difference was not significant. In nasal polyp tissue, there is a significant difference in TGF-β1 and IL-8 expression between CRSwNP and recurrent CRSwNP, where the expression of both cytokines is lower in recurrent CRSwNP. Interleukin-5 expression was higher in recurrent CRSwNP than CRSwNP, but the difference was not significant. In the polyps mucosal, IL-5 has the main role in recurrent CRSwNP polyp, whereas TGF-β has the main role in polyp tissue. CONCLUSION: This study concluded that the expression of IL-5 in the mucosa could be examined with simple techniques like brushing before polypectomy or FESS was performed to determine the possibility of polyps recurrencies.


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