Jichao Sha

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.

P-FN12, a novel H4R-based epitope vaccine obtained by screening a phage-display peptide library, regulates the Th1/Th2 balance in a rat model of allergic rhinitis

Allergic rhinitis (AR) involves antigen-specific immune-inflammation of the nasal mucosa. Classical therapy for AR targets the histamine pathway, e.g., histamine receptor blockers. Histamine H4 receptor (H4R) was suggested as a novel therapeutic target due to its wide expression on almost all immune-related cells. A 12-mer random peptide library was used to select the specific epitope of the H4R. The phage clone showing the highest degree of activation was verified and translated to the corresponding peptide. The peptide FNKWMDCLSVTH, designated as P-FN12, was bound by H4R monoclonal antibody (mcAb) with high affinity. Moreover, the P-FN12 + CTB@Lipo-formulated vaccine, used as nasal drops, decreased allergic symptoms such as sneezing and nasal rubbing in a rat model. The level of ovalbumin (OVA)-specific immunoglobulin E (IgE) decreased significantly after vaccine administration. It also elicited increased levels of interferon (IFN)-γ and interleukin-2 (IL-2) but a decreased level of IL-4, and it elevated the T helper type 1 (Th1):T helper type 2 (Th2) cell ratio in peripheral blood mononuclear cell cultures. Our results indicated that the reduction of allergic inflammation by P-FN12-based vaccine was related to a decrease in production of OVA-specific IgE, Th2 immunity, and tissue eosinophilia. P-FN12 + CTB@Lipo is a promising vaccine that could suppress Th2 response and enhance the induction of Th1 cells in an AR model.

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.

New therapeutic strategies in allergic rhinitis

Allergic rhinitis (AR) is a nasal inflammatory, IgE-mediated disease that occurs when some individuals inhales something he or she is allergic to, such as pollen or animal dander. It is also a refractory disease with high prevalence in the field of rhinology. The treatment of AR is really a difficult and challenging task because of the high prevalence, economic burden and the interference to the quality of life. At present, nasal corticosteroid and antihistamines were the mainly therapies, however, there is up to 40% patients not satisfactory to these therapies. So exploring new therapy or target is necessary. This article will review the results of previous studies focused on the new therapies of AR.