Reduction Of Total IgE Research Articles

Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence.

Already used for the treatment of some allergic and inflammatory diseases, such as asthma or atopic dermatitis, dupilumab has also been approved as add-on therapy for patients with CRSwNP, and it could represent the keystone to reducing the remission time as well as to improve healing and quality of life. On the other hand, the role of miRNAs as potential biomarkers of immune modulation is emerging. We analyzed the effects of a short-time treatment with dupilumab in patients with CRSwNP, analyzing the immune response modification as well as miRNAs modulations. First, in this early observation stage, all patients experienced remarkable improvement and were clinically stable. Indeed, we observed a significant decrease in CD4+ T cells and a significant reduction in total IgE (p < 0.05) and serum IL-8 levels (p < 0.01), indicating a reduction in the general inflammatory condition. In addition, we analyzed a panel of about 200 circulating miRNAs. After treatment, we noted a significant downregulation of hsa-mir-25-3p (p-value = 0.02415) and hsa-mir-185-5p (p-value = 0.04547), two miRNAs involved in the proliferation, inflammation, and dug-resistance, in accordance with the clinical status of patients. All these preliminary data aimed to identify new biomarkers of prognosis, identifiable with non-invasive procedures for patients. Further, these patients are still under observation, and others with different levels of responsiveness to treatment need to be enrolled to increase the statistical data.

Anti-allergic activities of 5,7-dimethoxy-3,4′-dihydroxyflavone via inhalation in rat allergic models

Various studies have shown that flavones have several pharmacological activities including anti-allergy activities. However, the bioavailability of oral flavones is very low, and whether inhaled administration can improve efficacy in respiratory disease models is unclear. In the present study, the anti-allergic activities of inhaling 5,7-dimethoxy-3,4′-dihydroxyflavone (MHF), a synthetic flavonoid, was investigated by comparison with disodium cromoglycate (DSCG) and nedocromil sodium (NS) in rat allergic models. In an anti-DNP-IgE-induced asthmatic model, inhaled MHF dose-dependently inhibited the increase in airway resistance after antigen challenge. In an ovalbumin (OVA)-induced asthmatic model, inhaled MHF showed significant suppression of airway hyperresponsiveness; a decrease in eosinophil and neutrophil counts, IL-4, IL-5 and leukotriene D4 in bronchoalveolar lavage fluid; a reduction in total IgE and OVA-specific IgE levels in serum; and suppression of eosinophil infiltration in lung tissue after antigen challenge. The efficacy of inhaled MHF was comparable to that of NS and DSCG. In conclusion, based on these findings, the report for the first time that that inhaled MHF may be a potential drug for the treatment of allergic asthma.

EVALUATION OF HUMORAL IMMUNITY IN PREGNANT WOMEN WITH ALLERGIC HISTORY

Background. The aim of the study was to evaluate humoral immunity and efficacy of diet therapy in pregnant women with allergic history. Methods. Monitoring group comprised 118 pregnant women. The study group included 83 pregnant women who received dietary correction of the diet with the inclusion of the New Zealand goat milk. The comparison group consisted of 35 pregnant women, dietary recommendations, with the inclusion in the diet of the cow’s milk (CM). The content of total serum IgE was detected using the immunoassay analyzer using monospecific reagent. Allergenspecific IgE antibodies to CM, βLH, casein and soy protein were determined by enzyme immunoassay analyzer using commercial kits «Allergopharma». Contents of immunoglobulins G, A, M in the serum were determined by nephelometry on immunochemical analyzer IMMAGE. Results. Unlike women from the comparison group half of pregnant women had a core group of allergic diseases, the majority of women in both groups were observed burdened obstetric history, indicating a decrease in their reproductive function. Dysfunctions of the gastrointestinal tract were observed in 34,7% of pregnant women in both groups, and the frequency in women with an allergy was 2,3 times higher than in women not suffering from allergic reactions. High levels of total IgE in serum were observed in the patients with allergy, diseases of the gastrointestinal tract, as well as their combination. The concentration of allergen specific IgE antibodies to proteins in cow’s milk was higher in women with IgEmediated allergies. In pregnant women with allergies and diseases of the gastrointestinal tract serum IgG and IgA levels were decreased. Conclusion. Application of hypoallergenic diet with cow’s milk replacement for New Zealand goat milk, as well as the exclusion of cow’s milk or a restriction in the diet of pregnant women caused a reduction of total IgE in the blood compared to previous treatment. Allergenspecific IgE antibodies to milk proteins decreased in the majority of women while dietary treatment.

Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcγRIIb with Fc-engineered antibody

Sequestration of IgE to prevent its binding to high-affinity IgE receptor FcεRI on basophils and mast cells is an effective therapy for allergic asthma. IgE production requires differentiation of activated IgE(+) B cells into plasma cells upon allergen sensitization. B-cell receptor signaling is suppressed by the inhibitory IgG Fc receptor FcγRIIb; therefore, we reasoned that a therapeutic antibody that coengages FcγRIIb and IgE B-cell receptor would not only sequester IgE but also suppress its production by blocking IgE(+) B-cell activation and differentiation to IgE-secreting plasma cells. To explore the effects of IgE sequestration versus IgE suppression by comparing omalizumab to FcγRIIb-optimized anti-IgE antibodies in humanized mouse models of immunoglobulin production. By using a murine anti-IgE antibody as a template, we humanized, increased IgE binding, and modified its Fc domain to increase affinity for FcγRIIb. We next compared effects of this antibody (XmAb7195) versus omalizumab on the secretion of IgE and other isotypes in human PBMC cultures and in PBMC-engrafted severe combined immunodeficiency mice. Relative to omalizumab, XmAb7195 has a 5-fold higher affinity for human IgE and more than 400-fold higher affinity for FcγRIIb. In addition to sequestering soluble IgE, XmAb7195 inhibited plasma cell differentiation and consequent human IgE production through coengagement of IgE B-cell receptor with FcγRIIb. In PBMC-engrafted mice, XmAb7195 reduced total human IgE (but not IgG or IgM) levels by up to 40-fold relative to omalizumab. XmAb7195 acts by IgE sequestration coupled with an FcγRIIb-mediated inhibitory mechanism to suppress the formation of IgE-secreting plasma cells and reduce both free and total IgE levels.

Reduction of Total IgE by Targeted Coengagement of IgE-BCR and FcgRIIb with Fc-Engineered Antibodies

RATIONALE: An IgE-mediated allergic response requires allergen-specific B-cell differentiation into IgE-producing plasma cells. We created XmAb7195, an omalizumab (Xolair) -related anti-IgE antibody Fc engineered for high affinity to human FcγRIIb, to coengage IgE-BCR and FcγRIIb and prevent activation and terminal differentiation of IgE+ B cells. Our hypothesis is that XmAb7195 will not only sequester free IgE, but will suppress its production and reduce total IgE.

Prenatal and early postnatal environments are significant predictors of total immunoglobulin E concentration in Filipino adolescents.

Recent evidence suggests that atopic disease may in part be mediated by fetal growth, as well as exposure to infectious disease early in life. Few studies have been able to evaluate these associations simultaneously, or to investigate prospectively the long-term effects of early environments while adequately controlling for potentially confounding variables. To examine how prenatal growth and infectious disease in infancy are related to total IgE production in adolescence. Ninety-nine adolescents (aged 14-15 years) were selected from a larger cohort study according to the following criteria: full-term birth, currently healthy, and small-for-gestational age (N=53) or appropriate-for-gestational age (N=46). Plasma total IgE was measured with ELISA, and analysed in relation to anthropometric, nutritional, and environmental quality data collected prospectively beginning in the third trimester prior to birth. Each episode of infectious morbidity recorded at bimonthly intervals in the first 6 months of life was associated with a 0.12 log IU/mL reduction in total IgE in adolescence (P=0.004). Prenatal undernutrition was associated with increased adolescent IgE, but only under conditions of an unsanitary household environment (P=0.002). Each additional kilogram gained per month in the first 6 months of life was associated with an increase in adolescent IgE of 0.74 log IU/mL (P=0.03). Each quartile increase in weekly household income at the time of blood sampling was associated with a 0.10 log IU/mL reduction in total IgE (P=0.02). Infectious disease in infancy, as well as interactions between prenatal and postnatal environments, appear to have long-term effects on adolescent total IgE production. Future research should investigate the mechanisms behind these effects, and their implications for symptoms of atopic disease.

Present and Potential Therapy for Allergic Rhinitis

Allergic rhinitis can affect up to one-fifth of the population and the economic impact is increasing. H(1) receptor antagonists were the first major pharmacologic treatment, but the associated sedation limited their use. The 2 initial second generation less sedating antihistamines, astemizole and terfenadine, were found to prolong the cardiac QT(c) interval, especially when administered with other medications metabolised by the same cytochrome (CYP) P450 isoenzyme, CYP3A4. Other second generation antihistamines, fexofenadine, loratadine and cetirizine, do not cause clinically significant cardiac QT(c) interval prolongation. Two newer agents, ebastine and mizolastine, are also effective in the treatment of allergic rhinitis. Ebastine, however, prolongs the cardiac QT(c) interval in laboratory animals and humans, the clinical significance of which is unknown. Desloratadine and norastemizole, metabolites of loratadine and astemizole, respectively, are 2 other second generation antihistamines found to be effective treatments for seasonal allergic rhinitis. Unlike their parent compounds, they do not prolong the cardiac QT(c) interval. All clinically available intranasal corticosteroids are effective in the treatment of allergic rhinitis, but studies to evaluate possible long term systemic adverse effects are limited. Mometasone furoate and fluticasone propionate have lower oral bioavailability compared with other corticosteroids that are given intranasally. This may be important, since it is likely that some of the intranasal corticosteroid is ingested. Two 1-year growth studies in children indicated that intranasal beclomethasone dipropionate given twice daily reduces growth velocity, whereas intranasal mometasone furoate given once daily in the morning does not. Other studies are needed. Most but not all studies have shown that leukotriene antagonists are effective in the treatment of allergic rhinitis. H(1) receptor antagonists are not very effective in reducing nasal congestion, but leukotriene antagonists do attenuate this symptom. Furthermore, one study demonstrates an additive benefit in treating allergic rhinitis with the combination of a H(1) receptor and leukotriene antagonist. Clinical trials have demonstrated that anti-immunoglobulin (Ig) E is effective in the treatment of seasonal allergic rhinitis when free IgE is reduced to <25 microg/L. The reduction of total IgE is dose dependent and subcutaneous and intravenous administration are both effective. Immunotherapy is also an effective treatment for allergic rhinitis. CpG oligonucleotides is a novel adjuvant for allergen immunotherapy. This adjuvant used in a murine model shifts the immune response away from the allergic or TH2 phenotype. Studies in humans have not been performed.