Objective To investigate the expression of blood basophil activation markers in patients with allergic rhinitis (AR) and the effects of allergens on their expression. Methods The blood samples were collected from the following four groups: healthy control (HC), AR patients with negative skin prick test (nAR), seasonal AR patients (sAR) and perennial AR patients (pAR). Flow cytometry was employed to analyze the expression of basophil activation markers Immunoglobulin E receptor I alpha(FcepsilonRIα), CD63 and CD203c in AR patients. Plasma levels of interleukin 4 (IL-4) and IL-8 were measured by liquid-phase chip technology, and their correlations with the percentages of activated basophils were further analyzed. An ovalbumin-induced AR mouse model was established, and the expression levels of FcepsilonRIα and CD63 on blood basophils were detected. Results The expression of FcepsilonRIα, CD203c and CD63 on basophils were increased in nAR, sAR and pAR patients. Allergens enhanced the mean florescence intensity expression of CD63 and CD203c on basophils of sAR and pAR patients. The plasma levels of IL-4 and IL-8 were elevated in nAR, sAR and pAR patients, showing moderate to high correlations with the expression levels of basophil activation markers. The FcepsilonRIαand CD63 expression on basophils of AR mice were increased. Conclusion Allergens may contribute to AR pathogenesis by upregulating the expression of FcepsilonRIα, CD63 and CD203c, as well as promoting the secretion of IL-4 and IL-8.
Basophils/metabolism* ; Humans ; Allergens/immunology* ; Animals ; Rhinitis, Allergic/blood* ; Female ; Male ; Adult ; Mice ; Biomarkers/blood* ; Tetraspanin 30/blood* ; Interleukin-4/blood* ; Interleukin-8/blood* ; Receptors, IgE/blood* ; Phosphoric Diester Hydrolases ; Young Adult ; Pyrophosphatases ; Middle Aged ; Mice, Inbred BALB C

Objective:To investigate the correlation between FCER2（2206A>G） gene polymorphism and the efficacy of inhaled corticosteroids（ICS） in patients with chronic rhinosinusitis（CRS）. Methods:A total of 208 CRS patients were routinely treated with functional endonasal sinus surgery and postoperative ICS. DNA extraction, PCR amplification and gene sequencing were performed to observe the FCER2（2206A>G） gene polymorphism and calculate the allele frequency. The visual analog scale（VAS） score, Lund-Kennedy score, and computed tomography（CT） Lund-Mackay score were determined 6 months after surgery among patients with different genotypes. Moreover, the polymorphism frequency was compared among different subgroups（chronic rhinosinusitis with nasal polyps versus chronic rhinosinusitis without nasal polyps, eosinophilic chronic rhinosinusitis versus non-eosinophilic chronic rhinosinusitis）. Results:There were FCER2（2206A>G） gene polymorphism in patients with CRS, and the phenotypes included 3 genotypes, AA, AG and GG, with distribution frequencies of 68（32.7%）, 116（55.8%） and 24（11.5%） cases, respectively. No significant differences were found in age, VAS score, nasal endoscopic Lund-Kennedy score and CT imaging Lund-Mackay score among patients with CRS of each genotype before surgery. In patients with the AA genotype, the changes in VAS score（5.74±1.10）, Lund Kennedy score（5.92 ± 1.14）, and CT imaging Lund-Mackay score（13.26±4.26） were significantly higher than in patients with the AG（4.37±0.86, 5.37±1.24, 10.82±3.77） and GG（4.26±0.80, 5.18±1.56, 10.10±3.53） genotype（P<0.05）. However, there were no marked difference between patients with the AG genotype and those with the GG genotype（P>0.05）. Compared with patients with non-eosinophilic sinusitis, Among them, the differences between the GG genotype and AG /AA genes were more significant in eosinophilic sinusitis compared to non-eosinophilic sinusitis（P<0.01）. Conclusion:The FCER2（2206A>G） gene in patients with CRS has genetic polymorphism and is associated with the recovery of CRS patients after surgery, individual corticosteroid sensitivity, and subgroup variability.
Humans ; Nasal Polyps/complications* ; Rhinitis/complications* ; Sinusitis/complications* ; Adrenal Cortex Hormones/therapeutic use* ; Polymorphism, Genetic ; Endoscopy/methods* ; Chronic Disease ; Receptors, IgE ; Lectins, C-Type

Aspergillus fumigatus ; Cytokines ; Humans ; Interleukin-1beta ; Keratitis ; Receptors, IgE ; Tumor Necrosis Factor-alpha ; Tumor Necrosis Factors

Chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria, is a common chronic inflammatory skin disorder that has a prevalence of 0.5% to 1% in the general population. It affects daily normal life and work productivity, with significant impacts on quality of life. Generally, the management of CSU uses a step-wise approach. Although second-generation H1 antihistamines are an effective mainstay of CSU, approximately 20% of patients are resistant to conventional antihistamine monotherapy. Evidence-based and expert consensus-based treatment guidelines of CSU can be a useful resource for primary care physicians and specialists. This review presents diverse information to support decision-making for individualized treatment plans in this special population. Several major therapeutic advances have occurred in recent years. Omalizumab, an immunoglobulin G humanized monoclonal anti-immunoglobulin E antibody that prevents binding of immunoglobulin E to the high-affinity immunoglobulin E receptor has shown safety and efficacy in patients with intractable CSU. In well-controlled clinical trials in patients with refractory CSU who received add-on therapy with subcutaneous omalizumab (300 mg every 4 weeks for 12 or 24 weeks), the rates of complete response were significantly higher in the omalizumab group (relative risk, 4.55; P < 0.0001). The introduction of omalizumab as an add-on therapy to H1 antihistamines as a management option has markedly improved the therapeutic possibilities for CSU and the quality of life of CSU patients. Nevertheless, many patients still do not tolerate or benefit from existing therapies, including omalizumab. There are ongoing studies investigating the treatment potential of novel therapeutic targets in CSU.
Efficiency ; Histamine Antagonists ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Omalizumab ; Physicians, Primary Care ; Prevalence ; Quality of Life ; Receptors, IgE ; Skin ; Specialization ; Urticaria

Interleukin (IL) 33, a member of the IL-1 superfamily, is an "alarmin" protein and is secreted in its active form from damaged cells undergoing necrotic cell death. Mast cells are one of the main effector cell types in allergic disorders. They secrete a variety of mediators, including T helper 2 cytokines. As mast cells have high-affinity IgE receptors (FcepsilonRI) on their surface, they can capture circulating IgE. IgE-bound mast cells degranulate large amounts of histamine, heparin, and proteases when they encounter antigens. As IL-33 is an important mediator of innate immunity and mast cells play an important role in adaptive immune responses, interactions between the two could link innate and adaptive immunity. IL-33 promotes the adhesion of mast cells to laminin, fibronectin, and vitronectin. IL-33 increases the expression of adhesion molecules, such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in endothelial cells, thus enhancing mast cell adhesion to blood vessel walls. IL-33 stimulates mast cell proliferation by activating the ST2/Myd88 pathway; increases mast cell survival by the activation of survival proteins such as Bcl-XL; and promotes the growth, development, and maturation of mast cell progenitors. IL-33 is also involved in the activation of mature mast cells and production of different proinflammatory cytokines. The interaction of IL-33 and mast cells could have important clinical implications in the field of clinical urology. Epithelial dysfunction and mast cells could play an important role in the pathogenesis of interstitial cystitis. Urinary levels of IL-33 significantly increase in patients with interstitial cystitis. In addition, the number of mast cells significantly increase in the urinary bladders of patients with interstitial cystitis. Therefore, inhibition of mast cell activation and degranulation in response to increase in IL-33 is a potential therapeutic target in the treatment of interstitial cystitis.
Adaptive Immunity* ; Allergy and Immunology ; Blood Vessels ; Cell Death ; Cystitis, Interstitial ; Cytokines ; Endothelial Cells ; Fibronectins ; Heparin ; Histamine ; Humans ; Immunity, Innate ; Immunoglobulin E ; Interleukin-1 ; Interleukins ; Laminin ; Mast Cells* ; Peptide Hydrolases ; Receptors, IgE ; Urinary Bladder ; Urology ; Vascular Cell Adhesion Molecule-1 ; Vitronectin

Increased FcepsilonR1alpha expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal controls. The relationship between the percentage of CD203c-expressing basophils and clinical parameters was analyzed. The mean basophil CD203c expression was significantly higher in CU patients than in healthy controls (57.5% vs 11.6%, P < 0.001). The basophil CD203c expression in severe CU patients was significantly higher than in non-severe CU (66.5% +/- 23.3% vs 54.0% +/- 23.3%, P = 0.033). Multiple logistic regression analysis indicated that both > or = 72% basophil CD203c expression and urticaria activity score (UAS)> or = 13 were significant predictors of severe CU (P = 0.005 and P = 0.032, respectively). These findings suggest that the quantification of basophil activation with CD203c at baseline may be used as a potential predictor of severe CU requiring another treatment option beyond antihistamines.
Adult ; Autoantibodies/blood ; Basophils/*immunology ; Female ; Flow Cytometry ; Humans ; Immunoglobulin E/blood/immunology ; Male ; Phosphoric Diester Hydrolases/biosynthesis/*immunology ; Pyrophosphatases/biosynthesis/*immunology ; Receptors, IgE/biosynthesis ; Urticaria/*immunology

This study aims to clarify out the anti-inflammatory mechanism of Qingfei Xiaoyan Wan. Chemical constituents of Qingfei Xiaoyan Wan identified by UPLC Q-TOF, were submit to Molinspiration, PharmMapper and KEGG bioinformatics softwares for predicting their absorption parameters, target proteins and related pathways respectively; and the gene chip and real time-PCR were carried out to investigate the expression of inflammatory genes on lung tissue of guinea pigs or human bronchial epithelial cell lines. The predicted results showed that 19 of the 24 absorbable constituents affected at 9 inflammation-related pathways through 11 protein targets; Qingfei Xiaoyan Wan treatment can significantly reduce the infiltration of cytokines through ERK1 gene and 5 inflammatory pathways (Focal adhesion, Fc epsilon RI, Toll-like receptors, NK cell-mediated cytotoxic, and ERK/MAPK). The results of real time-PCR further confirmed that the anti-inflammatory effects of Qingfei Xiaoyan Wan were due to active ingredients such as arctigenin, cholic acid and sinapic acid intervened focal adhesion, Fc epsilon RI signaling and ERK/MAPK pathways. The novel approach of 'drug-target-pathway' will present an effective strategy for the study of traditional Chinese medicines.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Asthma ; metabolism ; pathology ; Cell Line ; Cholic Acid ; pharmacology ; Coumaric Acids ; pharmacology ; Cytokines ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; Female ; Furans ; pharmacology ; Guinea Pigs ; Humans ; Inflammation ; metabolism ; Lignans ; pharmacology ; Lung ; pathology ; MAP Kinase Signaling System ; Male ; Random Allocation ; Receptors, IgE ; metabolism ; Toll-Like Receptors ; metabolism

OBJECTIVETo identify the immunohistochemical patterns of follicular dendritic cell (FDC) meshwork and Ki-67 labeling index in small B-cell lymphomas (SBLs) and their significance in differential diagnosis.

METHODSSixty-eight cases of SBLs were included collected from November 2008 to June 2012. The patterns of FDCs and Ki-67 expression were studied on paraffin sections by CD21, CD23 and Ki-67 immunohistochemistry. The characteristic staining patterns of FDCs and Ki-67 expression among different SBLs were analyzed statistically.

RESULTSThe age of SBL patients ranged from 28 to 85 years with a mean of 55.2 years. The male to female ratio was 1.2:1. Fifty-five cases involved only lymph nodes (80.9%), and the remaining cases involved multiple extra-nodal sites. Histological classification of the cases was made according to the 2008 WHO lymphoma classification criteria: 22 were low-grade follicular lymphomas (FLs, including grade 1 and grade 2), 19 marginal zone lymphomas (MZLs), 17 mantle cell lymphomas (MCLs), and 10 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLLs). FDC meshwork limited to the central part of neoplastic follicles was characteristic for FL (90.9%, 20/22). The germinal center FDC meshwork was destroyed primarily at periphery in MZL (14/19). The absence or scattered FDC clusters were typical of SLL/ CLL. Irregular FDC was seen in 7/17 of MCL, while 7/17 MCL displayed FDC pattern similar to that of CLL/SLLs. The pattern of FDCs was a significantly diagnostic feature in distinguishing the four types of SBLs (P < 0.01). Ki-67 was also a statistically significant parameter (P < 0.05) with decreasing labeling index as the following: MCL, FL, SLL and MZL. Ki-67 showed scattered pattern in germinal centers with loss of polarity in FLs. MZL presented uniformly scattered positive pattern in interfollicullar areas. Ki-67 staining was uniform in MCL, but its labeling index varied from 5% to 90%. The Ki-67 index was higher in the morphological "proliferation centers" of all CLL/SLLs.

CONCLUSIONImmunohistochemical staining patterns of FDC meshworks and Ki-67 labeling index offer a significant discriminatory power in the differential diagnoses among SBLs.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Dendritic Cells, Follicular ; pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Lymphoma, B-Cell ; classification ; metabolism ; pathology ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; pathology ; Lymphoma, Follicular ; metabolism ; pathology ; Lymphoma, Mantle-Cell ; metabolism ; pathology ; Lymphoma, Non-Hodgkin ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, Complement 3d ; metabolism ; Receptors, IgE ; metabolism ; Retrospective Studies

OBJECTIVE: To construct a special luciferase reporter to detect DNA methylation regulatory activity in FCER1G gene promoter regulatory element. METHODS: We constructed special full and mock methylated FCER1G gene promoter regulatory luciferase reporters by patch-methylation, and detected DNA methylation regulatory activity by comparing the luciferase activity of full-methylated luciferase reporters with mock-methylated reporters. RESULTS: We successfully constructed the full and mock methylated FCER1G gene promoter regulatory luciferase reporters. The ratio of luciferase activity between the full methylated and the mock methylated was (0.36±0.07):1 (P<0.001). CONCLUSION FCER1G promoter activity is methylation-sensitive and is regulated by DNA methylation.
Base Sequence ; DNA Methylation ; Gene Expression Regulation ; Genes, Reporter ; Humans ; Luciferases ; genetics ; Molecular Sequence Data ; Promoter Regions, Genetic ; genetics ; Receptors, IgE ; genetics ; metabolism

OBJECTIVETo analyze the frequency distribution of single nucleotide polymorphisms (SNPs) of four asthma-related gene loci (ACE I/D; ADRB2 Arg16Gly; TNF-α G-308A; MS4A2 Glu237Gly) in 198 asthmatic children, and to investigate its association with genetic susceptibility to childhood asthma and some clinical phenotypes of asthma.

METHODSPolymerase chain reaction product electrophoresis identification and real-time quantitative PCR detecting system were used to determine the frequency distributions of the SNPs of the four asthma-related gene loci in 198 asthmatic children and 110 healthy controls. The serum total IgE (TIgE) levels and blood eosinophil proportion (%EOS) of the asthmatic children were measured. Different genotypes at the four asthma-related gene loci were compared in terms of TIgE and %EOS.

RESULTSThe genotype DD of angiotensin-converting enzyme (ACE) had a significantly higher frequency in the asthmatic children than in the healthy controls (χ2= 30.667, P<0.01), and the frequency of D allele was also significantly higher in the asthmatic children than in the healthy controls (χ2=7.151, P<0.01). No correlation was found between the polymorphism of each gene locus and serum TIgE level and %EOS (P>0.05).

CONCLUSIONSGenotype DD of ACE is related to genetic susceptibility to childhood asthma and may be the risk factor for childhood asthma.

Asthma ; etiology ; genetics ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, beta-2 ; genetics ; Receptors, IgE ; genetics ; Tumor Necrosis Factor-alpha ; genetics