Childhood minimal change nephrotic syndrome (MCNS) has often been associated with allergic symptoms such as urticaria, bronchial asthma, atopic dermatitis, allergic rhinitis and elevated IgE levels and referred to involve immune dysfunction. Fc epsilon RII is known to be involved in IgE production and response. Interleukin-4 is being recognized as a major cytokine up-regulating IgE production. Hence the present study is aimed at investigating the role of interleukin-4 and Fc epsilon RII in the pathogenesis of MCNS. IgE was measured by ELISA. Fc epsilon RII was analyzed by fluorescence activated cell scanner (FAC-scan) by double antibody staining with anti Leu16-FITC and anti Leu20-PE. Soluble IgE receptor was measured by ELISA using anti CD23 antibody (3-5-14). Interleukin-4 activities were measured by CD23 expression on purified human tonsillar B cells. Serum IgE levels were significantly higher in MCNS (1,507 +/- 680 IU/dl) than in normal controls (123 +/- 99.2 IU/dl). A significantly higher expression of membrane Fc epsilon RII was noted for MCNS (41 +/- 12%) than that in normal controls (18 +/- 6.2%) (p < 0.001). Soluble CD23 levels were also significantly higher in MCNS (198 +/- 39.3%) than in normal controls (153 +/- 13.4) (p < 0.01). Interleukin-4 activity in sera of MCNS (12U/ml) was also significantly higher than normal controls (4.5U/ml). These results indicate that increased production of Fc epsilon RII and interleukin-4 may play an important role in the pathogenesis of MCNS.
B-Lymphocytes/immunology ; Child ; Humans ; Immunoglobulin E/blood ; Interleukin-4/*physiology ; Nephrosis, Lipoid/*etiology/physiopathology ; Receptors, IgE/biosynthesis/*physiology ; Solubility

B-Lymphocytes ; chemistry ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Purpura, Schoenlein-Henoch ; immunology ; Receptors, IgE ; blood

BACKGROUND: Allergen-specific immunotherapy has been shown to be clinically effective in the treatment of patients with atopic asthma, but the mechanisms are still unclear. Some of the immunologic changes include increase of an allergen-specific IgG antibody, decrease of allergen-specific IgE after transient increase, allergen-specific T-cell shift in cytokine expression from Th2 to Th1 cytokines, and decrease of basophil histamine releasability. OBJECTIVE: To investigate the influence of immunotherapy on basophil releasability, we examined the changes of IgE-mediated and non-IgE-mediated basophil histamine releasability during immunotherapy. METHODS: Fourteen Dermatophagoides farinae (D.f) sensitive asthmatic children with conventional immunotherapy were investigated. Basophil histamine releasability was measured prior to immunotherapy and 4 and 9 months after immunotherapy. Basophils were stimulated with D.f and goat antihuman IgE antibody as IgE-mediated stimuli which act on IgE-receptor, and formyl-Met-Leu-Phe (fMLP) as non-IgE-mediated stimuli which acts on non-IgE receptor, and calcium ionophore A23187 as non-IgE-mediated stimuli which does not act on cell surface receptors. Histamine was measured by automated fluorometric technique. RESULTS: Before immunotherapy, there were significant correlations between histamine release by D.f and histamine release by fMLP, and between histamine release by D.f and histamine release by anti-IgE antibody, but no correlation between histamine release by D.f and histamine release by calcium ionophore. Histamine release by D.f and by anti-IgE antibody decreased at and 9 months after immunotherapy compared to those before immunotherapy. Histamine release by fMLP and by calcium ionophore showed no significant changes after immunotherapy. There was no significant change of total histamine release after immunotherapy. CONCLUSION: Conventional immunotherapy has influenced only the IgE-mediated basophil releasability. IgE-mediated and non-IgE-receptor-mediated basophil releasability was correlated before immunotherapy, but only IgE-receptor-mediated basophil releasability decreased after immunotherapy. These findings suggest that a kind of physicochemical change may happen on the IgE receptors of basophil, which may induce decrease of IgE-mediated basophil histamine releasability after immunotherpy.
Asthma ; Basophils* ; Calcimycin ; Calcium ; Child ; Cytokines ; Dermatophagoides farinae ; Goats ; Histamine Release ; Histamine* ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Immunotherapy* ; Receptors, Cell Surface ; Receptors, IgE ; T-Lymphocytes

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

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

OBJECTIVETo investigate the association of the polymorphism of I181L, V183L and E237G in the high affinity immunoglobulin E receptor beta-chain (FcepsilonR1beta) with the susceptibility of childhood asthma and the serum total immunoglobulin E (IgE) level.

METHODSThe coding variants of I181L, V183L and E237G and the serum total IgE level were detected using amplification refractory mutation systemdouble ended arrowpolymerase chain reaction (ARMS-PCR) and double antibody sandwich ELISA respectively in 50 asthmatic children and 40 normal controls from Sichuan Province. The association of gene mutation with the susceptibility of asthma and the serum total IgE level was analyzed.

RESULTSThere were 5 cases of I181L mutation, 2 of V183L mutation, and 7 of E237G mutation in the Asthmatic group. There was no mutation in the Normal control group. The frequency of I181L and E237G mutation in the Asthmatic group were statistically higher than in the Normal control group (P < 0.01). The serum total IgE level in the Asthmatic subgroup with I181L mutation (2.837 +/- 0.407) or E237G mutation (3.044 +/- 0.419) was significantly higher than in the Asthmatic subgroup without gene mutation (2.156 +/- 0.638) and the Normal control group (1.348 +/- 1.291) (P < 0.05 or 0.01).

CONCLUSIONSThe polymorphism of Fc epsilonR1betaI181L and E237G is a susceptible gene of childhood asthma and closely associates with the increased serum total IgE level.

Adolescent ; Asthma ; genetics ; immunology ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Humans ; Immunoglobulin E ; blood ; Infant ; Male ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, IgE ; genetics

Antigens, CD19 ; analysis ; Asthma ; blood ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Immunoglobulin E ; blood ; Lymphocytes ; immunology ; Male ; Receptors, IgE ; analysis

OBJECTIVE: To explore the expression of CD23, CD19 on peripheral blood lymphocytes as well as its association with serum total IgE levels and nasal allergic symptoms in patients with allergic rhinitis (AR). METHOD: Symptom scores were evaluated in 46 AR patients, expression of CD23, CD19 on peripheral blood lymphocytes were measured by flow cytometry, and serum total IgE levels were determined by immune chemiluminescence. Thirty two healthy individuals were enrolled as controls. RESULT: The percentage of CD23+, CD19+ and CD23+/ CD19+,on peripheral blood lymphocytes in AR patients were 11.6 +/- 1. , 22.8 +/- 3.3,10.2 +/- 1.7, respectively. Higher frequencies of CD23+, CD19+, and CD23+/CD19+ were found in AR patients compared with controls (P < 0.05). There were positive correlations between expression rates of CD23+, CD19+, CD23+/CD19+ and levels of serum total IgE, nasal allergic symptom scores, respectively. CD23+/CD19+ demonstrated greater correlations with serum total IgE and nasal allergic symptom (r = 0.65 and 0.49, P < 0.05) than CD23+ and CD19+ did. Correlation between CD23+/CD19+ and nasal allergic symptom scores was greater than the corresponding correlations of serum total IgE (r = 0.33, P < 0.05). CONCLUSION CD23 and CD19 are important factors that associated with serum total IgE in the pathogenesis of AR, Analysis on the expression of CD23+/CD19+ on peripheral blood lymphocytes is helpful for evaluating the severity of AR.
Adolescent ; Adult ; Antigens, CD19 ; blood ; Case-Control Studies ; Female ; Humans ; Immunoglobulin E ; blood ; Lymphocyte Count ; Lymphocytes ; metabolism ; Middle Aged ; Receptors, IgE ; blood ; Rhinitis, Allergic, Perennial ; blood ; Young Adult

Japanese hop (Hop J) pollen has been considered as one of the major causative pollen allergens in the autumn season. We developed a new Hop J immunotherapy extract in collaboration with Allergopharma (Reinbeck, Germany) and investigated immunologic mechanisms during 3 yr immunotherapy. Twenty patients (13 asthma with rhinitis and 7 hay fever) were enrolled from Ajou University Hospital. Sera were collected before, 1 yr, and 3 yr after the immunotherapy. Changes of serum specific IgE, IgG1 , and IgG4 levels to Hop J pollen extracts and serum IL-10, IL-12, TGF-beta1 and soluble CD23 levels were monitored by ELISA. Skin reactivity and airway hyper-responsiveness to methacholine were improved during the study period. Specific IgG1 increased at 1 yr then decreased again at 3 yr, and specific IgG4 levels increased progressively (p<0.05, respectively), whereas total and specific IgE levels showed variable responses with no statistical significance. IL-10, TGF-beta1 and soluble CD23 level began to decrease during first year and then further decreased during next two years with statistical significances. (p<0.05, respectively). In con-clusion, these findings suggested the favorable effect of long term immunotherapy with Hop J pollen extracts can be explained by lowered IgE affinity and generation of specific IgG4 , which may be mediated by IL-10 and TGF-beta1.
Transforming Growth Factor beta/blood ; Receptors, IgE/blood ; Pollen/*immunology ; Poaceae/*immunology ; Interleukin-10/blood ; Immunoglobulin G/blood ; Immunoglobulin E/blood ; Humans ; *Desensitization, Immunologic ; Cytokines/*blood ; Bronchial Hyperreactivity/etiology

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