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1.

Background

IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS).

Methods

IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course.

Results

IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field.

Conclusions

Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course.  相似文献   
2.

Background

IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS).

Methods

Dispersed nasal polyp (NP) cells and uncinate tissue (UT) cells were prepared from patients with CRS with and without NP, respectively. Cells were incubated with SEB, and then the levels of IL-10 in the cell supernatants were determined. The effect of neutralizing IL-10 on SEB-induced IL-5, IL-13, IFN-γ, and IL-17A production was examined. Expression of IL-10 in NPs was also determined.

Results

IL-10 was expressed in infiltrating inflammatory cells in NPs. NP cells, especially non-adherent NP cells, produced substantial amounts of IL-10 in response to SEB. Although baseline production of IL-10 was significantly higher in NP cells than UT cells, the degree of IL-10 response to SEB was not significantly different between the cell types. The degree of IL-10 production was negatively correlated with the degree of eosinophilia both in tissues and peripheral blood whereas positively correlated with the 1-s forced expiratory volume/forced vital capacity ratio. Patients with severe ECRS displayed a significant decrease in IL-10 production compared with those with non-ECRS. IL-10 neutralization significantly augmented SEB-induced IL-13 and IFN-γ production by NP cells.

Conclusions

Impaired IL-10 production in response to SEB in NP may exacerbate the pathophysiology of ECRS including eosinophilia and lower airway obstruction.  相似文献   
3.
《Immunobiology》2020,225(2):151890
Chronic rhinosinusitis is an inflammatory process of the mucous membrane of the nasal cavity and paranasal sinuses, presenting with two phenotypes that differ in symptoms and inflammatory profiles: either with or without polyps. Natural killer (NK) cells are involved in both the innate and acquired immune response, and their function may be limited under pathological conditions, leading to polyp formation. We determined NK cell involvement and maturity in chronic rhinosinusitis, by determining the percentage of NK cells in polyps, nasal mucosa, and in the peripheral blood. Material was obtained from 49 patients with chronic rhinosinusitis (36 with polyps, 13 without polyps), and 15 control patients. Flow cytometry was used to immunophenotype NK cells, and the expression of selected functional receptors was evaluated. NK cells were found to be increased in polyp tissue versus peripheral blood and nasal mucosa. NK cell maturation differed significantly with predominance of a cytotoxic phenotype (CD11b+/27-) in peripheral blood, compared with a regulatory/tolerogenic phenotype (CD11+/-/ 27+) in tissue material. These findings demonstrate the involvement of NK cells in the inflammatory process of chronic rhinosinusitis. Decreased expression of activating receptors in the analyzed groups may also indicate the presence of modifying agents. Disorders of the maturation process of NK cells may be an important element in the etiopathogenesis of chronic rhinosinusitis with and without polyps.  相似文献   
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目的:探讨血清sIgE、总IgE浓度梯度、嗜酸粒细胞(EOS)与慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)发生的危险因素以及临床指标的筛选。方法:将152例慢性鼻-鼻窦炎患者分为慢性鼻-鼻窦炎不伴鼻息肉(CRSs—NP)组和CRSwNP组,行体外20种过敏原筛查,测定血清sIgE、总IgE、EOS百分比。结果:①CRSsNP患者血清总IgE浓度主要集中在1级,而CRSwNP患者血清总IgE浓度主要集中在2、3级(Z=0.906,P〉0.05)。分别比较两组患者血清sIgE分级.差异无统计学意义(P〉0.05)。②CRSwNP患者EOS百分比明显高于CRSsNP患者(F=4.337,P=0.039;t=3.315,P〈0.01)。且CRSwNP患者E0s百分比95%可信区间为3.90%~5.26%,5%TM值为4.3%,高于CRSsNP组及正常值。CRSwNP组患者EOS百分比,按sIgE值分梯度(分级)后,CRSwNP各组(级)之间比较差异均无统计学意义(P〉0.05)。③CRSwNP患者变应原多为混合型变应原,并且随着变应原浓度梯度的升高,混合型变应原过敏的CRSwNP组患者比例高于CRSsNP患者(χ2=8.595,P〈20.05)。结论:CRSwNP的发牛与EOS、混合变应原的存存有关。且当EOS百分比在3.90%~5.26%范围内CRSwNP更易发生。而血清总IgE、sIgE浓度不能单独作为CRswNP的发生因素。利用过敏原筛查结果结合临床症状,能更早地了解并远离过敏原,利于慢性鼻鼻窦炎围手术期治疗方案的制定。  相似文献   
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10.

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized as a Th2-driven disease.Activated dendritic cells (DCs) are the main T-cell activators; their role in the chronic inflammatory process of nasal polyposis is still unclear.

Methods

The regulation of DC subsets was analyzed in nasal polyp tissue from CRSwNP patients and compared to inferior turbinate tissue from healthy subjects. Tissue localization and expression of both plasmacytoid and myeloid DCs were assayed by means of immunohistochemistry and flow cytometry. Plasmacytoid DCs were also assayed by PCR, and tissue homogenates were assayed for various inflammatory markers.

Results

The number of plasmacytoid (pDCs) and myeloid (mDCs) dendritic cells was significantly increased in nasal polyp tissue when compared to non-inflamed nasal mucosa. The number of pDCs, but not mDCs, was down-regulated in more severe cases (nasal polyps with asthma) and varied with the cytokine milieu. The amount of pDCs was significantly decreased in IL5+IFNγ – nasal polyp tissue compared to tissues with high IFNγ levels (IL5+IFNγ+). Furthermore, levels of indoleamine 2,3-dioxygenase were increased in nasal polyp compared to inferior turbinate tissue and correlated negatively with the number of pDCs.

Conclusions

There is an altered balance of pDC and mDC numbers in nasal polyp tissue. pDCs seem to be more susceptible to an inflammatory cytokine milieu and may play a crucial role in disease severity.  相似文献   
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