Dongdong Zhu

The characterization of IL-17A expression in patients with chronic rhinosinusitis with nasal polyps.

Background Interleukin (IL)-17A, mainly produced by Th17 cells, was previously described as an inflammatory cytokine that induces a profile of proinflammatory cytokines, chemokines, and metalloproteinases. Recent studies have revealed that IL-17 is correlated with inflammatory lung disorders by triggering an accumulation of neutrophils. More recently, we have shown that the expression of IL-17 may be involved in the development of nasal polyps (NPs). Here, we describe the characterization of IL-17 expression in patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) from northeast China. Methods Histopathological observations and immunohistochemical (IHC) staining for IL-17, IL-17RD, myeloperoxidase, and CD68 were performed on 52 specimens (42 NPs and 10 specimens of middle turbinate as normal control). Double IHC staining was performed to determine which cells expressed IL-17. The serum expression levels of IL-17 were determined by ELISA and the mRNA expression of IL-17 and Th17 cells transcription factor retinoid acid–related orphan receptor C (RORc) was determined by real-time quantitative polymerase chain reaction. Results 42.9% of CRSwNP specimens presented eosinophilic inflammation; 35.7% of CRSwNP specimens presented neutrophilic inflammation. Relatively higher mRNA expression levels of IL-17 and RORc were seen in CRSwNPs compared with the controls. A marked increase of IL-17 and IL-17RD proteins (p < 0.01) were seen in CRSwNP group. The expression levels of IL-17 and RORc did not differ between eosinophilic and noneosinophilic CRSwNPs (p > 0.05). However, high expression levels of IL-17RD were seen in noneosinophilic CRSwNPs compared with eosinophilic CRSwNPs (p < 0.05). The serum expression of IL-17 in CRSwNP patients was similar to healthy controls. The IL-17 expressing cells mainly were the macrophages as shown by double IHC staining. Conclusion Chinese CRSwNP patients showed an enhanced Th17 response regardless of eosinophilic or noneosinophilic inflammation. IL-17 may be involved in the development of NPs through its local immune modulation.

Correlation analysis of two serum-specific immunoglobulin E test systems and skin-prick test in allergic rhinitis patients from northeast China.

Background Skin-prick testing (SPT) is the most common screening method for allergy evaluation. The detection of serum-specific immunoglobulin E (sIgE) is also commonly used. The sensitivity and specificity of these testing methods may vary due to type of causative allergen and type of allergic manifestation. The purpose of this study was to evaluate the correlation between two methods of measuring sIgE (AllergyScreen [Mediwiss Analytic GmbH, Moers, Germany] and ImmunoCAP [Pharmacia, Uppsala, Sweden]) and SPT for the diagnosis of allergic rhinitis (AR). Methods All 216 patients who were referred to the allergist for suspected AR from June to October 2009 had SPT and the two serological tests. One hundred fifty-eight patients had a positive clinical history and a related positive SPT. The SPT was used as reference standard, and we selected three allergens (Dermatophagoides pteronyssinus, mugwort, and ragweed), which were common in fall in northeast China, to analyze the correlation of the two serum tests and SPT. Results Compared with the SPT, the diagnostic indexes (accuracy, sensitivity and specificity) of the AllergyScreen system and the ImmunoCAP system were 0.819 versus 0.810, 0.780 versus 0.872, and 0.862 versus 0.741, respectively. The accuracy was similar between the two systems (p > 0.05). The ImmunoCAP system method had a higher sensitivity (p < 0.01). The AllergyScreen system had a higher specificity (p < 0.01). Conclusion These data support that the AllergyScreen system and ImmunoCAP system can identify potentially significant allergens in the diagnosis of AR in patients from northeastern China.

Effects of minimal persistent inflammation on nasal mucosa of experimental allergic rhinitis.

Background Minimal persistent inflammation (MPI) is considered another piece of the complex puzzle of allergic inflammation. Although some studies regarding MPI have been reported, no study has evaluated the effects of MPI on the structure changes at the site of allergic reaction. This study investigates whether long-time MPI during allergic rhinitis (AR) results in some features of tissue remodeling in the nasal mucosa. Methods An animal model of MPI was developed by repeated nasal challenge with low concentration of ovalbumin (OVA) in sensitized guinea pigs. The models were assessed by allergic symptom after antigen challenge, eosinophil infiltration in the nasal mucosa, and intercellular adhesion molecule (ICAM) 1 expression on nasal epithelial cells. The histopathological changes in nasal mucosa were determined by Alcian blue—periodic acid–Schiff and Massons trichrome staining. The expression of transforming growth factor (TGF) β1 and matrix metalloproteinase (MMP) 9 was examined by immunofluorescence under a confocal laser scan microscope. Results When sensitized animals were challenged with the low concentration of 0.01% OVA, the symptom of sneezing disappeared, but there were still mild eosinophils infiltration and weak ICAM-1 expression, which indicated the success of MPI models. Moreover, the number of goblet cells and the percentage area of collagen deposition were both mildly increased. The expression of MMP-9 and TGF-β1 was also weakly elevated. Conclusions We have successfully established MPI models and proved long-time MPI may result in mild features of remodeling in the nasal mucosa, which provide new insights into the unexpected potential effects of MPI on the structural changes.

The expression and significance of immunoglobulin free light chain in the patients with allergic rhinitis and nonallergic rhinitis.

Background Inflammation has been shown to be an integral component of allergic rhinitis (AR). However, there is no n worth debate regarding this fact in nonallergic rhinitis (NAR). Some studies have suggested that exclusion of inflammation is indicative of NAR and other studies have indicated that most of the NAR patients have some degree of inflammation. Recently, it has been shown that the level of immunoglobulin free light chains (IgFLCs) in serum is increased in some autoimmune diseases and airway inflammation. This study was designed to show whether IgFLC is associated with non–IgE-mediated rhinitis to reveal the relationship between the expression of IgFLC and activation of mast cells and eosinophils. Methods Thirty patients with IgE-mediated AR and 30 patients with NAR and 30 healthy persons as control were involved this study. The total IgE, IgFLC, eosinophil cationic protein (ECP) and mast cell tryptase (MCT) in serum, and nasal secretions were assayed, respectively. For identifying the expression cells of IgFLC in nasal mucosa, the immunohistochemical (IHC) staining for kappa-FLC, gamma-FLC, ECP, and MCT were performed on 30 specimens. Meanwhile, the mRNA expression of kappa-FLC, gamma-FLC, and MCT was determined by real-time quantitative polymerase chain reaction. Results IgFLCs (kappa/lambda) levels in serum and nasal secretion were significantly increased in AR patients and NAR patients. The ECP and MCT levels in serum and nasal secretion were significantly enhanced in AR and NAR patients when compared with healthy control subjects (p < 0.01). There was a positive correlation between IgFLC (kappa/lambda) and MCT n nasal secretion of patients with NAR, but only IgFLC (kappa-FLC was associated with MCT in AR. There was no correlation between IgFLC and ECP in nasal secretion. In serum expression level, there was a positive correlation between IgFLC (kappa) and ECP in AR or IgFLCs (lambda) and ECP in NAR. IHC staining showed that FLC+ cells were significantly increased in AR and NAR mucosa, kappa-FLC was mainly expressed in epithelial cells, and lambda-FLC was mainly expressed in subepithelial cells. Double immunofluorescence staining showed that the expression of lambda-FLC was mainly localized in mast cells in NAR nasal mucosa (45%). Conclusion These findings suggest strongly that IgFLC may play an important role in inducing local nasal mucosa inflammation especially those in AR and NAR.

Hypoxia regulates IL-17A secretion from nasal polyp epithelial cells

Hypoxia creates a microenvironment conducive to polypogenesis by regulating immune responses of the nasal polyp (NP) epithelium. We explored the immunocompetence of NP and control epithelial cells in response to hypoxia, to investigate potential relationships with polypogenesis. Three groups of tissue samples were collected: inferior turbinate (IT)and NP from individuals with chronic rhinosinusitis with NPs (CRSwNP), and control IT. A positive relationship was detected between HIF1α, HIF2α protein expression in epithelial cells and endoscope score in NP samples, while there was a negative correlation between HIF1α expression and degree of eosinophil infiltration. Epithelial IL-17A expression was lower in NPs than in IT samples from either controls or patients with CRSwNP. Primary human nasal epithelial cells were cultured under hypoxic or normoxic conditions. Enzyme-linked immunosorbent assays demonstrated decreased IL-17A expression upon prolonged exposure to hypoxia in both IT and NP samples from patients with CRSwNP, while IL-17A increased in control IT epithelial cells; correlation and time-dependency were observed between HIF1α and IL-17A expression in both IT and NP samples from patients with CRSwNP. These observations suggest that hypoxia is involved in the pathogenesis of NPs through regulation of IL-17A secretion and HIF1α and HIF2α expression in the NP epithelium.

Correlation of Serum β-Endorphin and the Quality of Life in Allergic Rhinitis

Background. Allergic rhinitis (AR) significantly impairs the quality of life of the patients; however, a questionnaire alone is an insufficient and subjective measure of this condition. Obtaining an objective clinical assessment of the level of impairment will be valuable for its treatment. β-Endorphin is one of the most important mediators of both mental state and specific immunity. Thus, we investigated the possibility of using β-endorphin as a biomarker for evaluating the impairment level in AR. Methods. This study included 48 patients with AR and 32 healthy volunteers. The serum β-endorphin level was determined by enzyme immunoassay, and the serum-specific IgE and total IgE levels were determined by immunoblot assay. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to assess the impairment level in the symptom duration. Results. The β-endorphin concentration was significantly decreased in AR patients compared to the healthy controls (p = 0.000, p < 0.05). There was significant negative correlation between the impairment level and serum β-endorphin level (correlation coefficient: −0.468; p = 0.001; p < 0.05), but there was no association between the serum β-endorphin and total IgE levels (p = 0.947, p > 0.05). Conclusion. β-Endorphin is a systemic biomarker that has the potential to assess the impairment level in AR and may therefore be a novel therapeutic target for the treatment of AR.