Increased estrogen to androgen ratio enhances immunoglobulin levels and impairs B cell function in male mice

Sex steroids, such as estrogens and androgens, are important regulators of the humoral immune response. Studies in female mice have demonstrated that alteration of circulating estrogen concentration regulates antibody-mediated immunity. As males have normally little endogenous estrogen, we hypothesized that in males high estrogens and low androgens affect the immune system and enhance the allergic inflammatory response. Here, we studied transgenic male mice expressing human aromatase (AROM+). These animals have a high circulating estrogen to androgen ratio (E/A), causing female traits such as gynecomastia. We found that AROM+ male mice had significantly higher plasma immunoglobulin levels, particularly IgE. Flow cytometry analyses of splenocytes revealed changes in mature/immature B cell ratio together with a transcriptional upregulation of the Igh locus. Furthermore, higher proliferation rate and increased IgE synthesis after IgE class-switching was found. Subsequently, we utilized an ovalbumin airway challenge model to test the allergic response in AROM+ male mice. In line with above observations, an increase in IgE levels was measured, albeit no impact on immune cell infiltration into the lungs was detected. Together, our findings suggest that high circulating E/A in males significantly alters B cell function without any significant enhancement in allergic inflammation.

Assessment of the cytokine profile in patients with allergic rhinitis caused by sensitization to house dust mite

The aim of the study was to evaluate the serum cytokine profile of patients with allergic rhinitis (AR) sensitized to house dust mites and to establish their role in the regulation of IgE synthesis Materials and Methods. The study included 60 patients with AR at the age of 20-60. According to the level of total IgE (IgE>100 kU/L), patients were divided into two groups with an IgE-dependent and IgE-independent form of AR. In the study, the serum levels of IL-2, g-IFN, IL-4, IL-5, IL-13, IL-10 and TGF-b in the blood serum were determined by ELISA. Results. According to the study, it was found that patients with an IgE-dependent form of AR are characterized by a decrease in the level of Th1 cytokines IL-2 and g-IFN, an increase in the level of Th2 cytokines – IL-4, IL-5 and IL-13 and a decrease in Treg cytokines – IL-10 and TGF- b. At the same time, a significant decrease in the level of inhibiting cytokine IL-10 was established in comparison with the group of patients with an IgE-independent form of AR. For patients with an IgE-independent form, only elevated levels of IL-13 were found. No significant differences were found between other Th1 and Th2 and Treg cytokines. Conclusions. The study showed that in patients with AR sensitization to house dust mites, IL-13 acts as a key cytokine in the IgE-independent form of AR, which can be important in the future for both predicting and treating AR.

Protein crystallization promotes type 2 immunity and is reversible by antibody treatment

Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies.

Potential Beneficial Effects of Wine Flavonoids on Allergic Diseases

Wine, a widely consumed beverage, comprises several biophenols that promote health. Flavonoids, majorly present in red wine, have been shown to have antioxidant, anti-inflammatory, anticancer, and immunomodulatory activities. Regular consumption of red wine (100 mL/day) is estimated to provide an average of 88 mg of flavonoids, whereas recent epidemiological studies indicate that wine is one of the major sources of flavonoid intake amongst wine lovers in European countries (providing an average intake of 291–374 mg/day of flavonoids). In addition to being antioxidants, in vitro studies suggest that flavonoids also have anti-allergic activities that inhibit IgE synthesis, activation of mast cells and basophils or other inflammatory cells, and production of inflammatory mediators, including cytokines. Furthermore, they affect the differentiation of naïve CD4+ T cells into effector T cell subsets. Moreover, several studies have reported the benefits of flavonoids in allergic models such as atopic dermatitis, asthma, anaphylaxis, and food allergy; however, evidence in humans is limited to allergic rhinitis and respiratory allergy. Although further evaluation is required, it is expected that an appropriate intake of flavonoids may be beneficial in preventing, and eventually managing, allergic diseases.

IMPACT OF ENVIRONMENTAL POLLUTION ON THE PREVALENCE OF ALLERGIC DISEASES AMONG THE EMPLOYEES OF INDUSTRIAL SITES LOCATED AT FORMER URANIUM ORES MINES

The article presents the study of prevalence of allergic diseases among the employees of industrial sites located at former uranium ores mines in Lermontov region. The aim of the research was to study the spectrum of etiologically significant allergens, prevalence and clinical features of allergic diseases among the employees of industrial sites located at former uranium ores mines in Lermontov region. Materials and Methods. Analysis of data of screening questioning, clinical laboratory, functional and allergological methods of examination was performed. Results. The high prevalence of allergic diseases among employees of hydrometallurgical plant (OJSC GMP) and electromechanical plant (LLC EMP): 27,1 and 24,7%, respectively was found. Two employees of OJSC GMP and one of LLC EMPin 2014 had latent sensitization to pollen, but in 2015 demonstrated severe clinical symptoms of allergic rhinitis (AR). Conclusion. Respiratory forms of Ig-Emediated allergy - AR, bronchial asthma (BA) prevailed in the structure of allergic diseases among the employees of industrial sites located at former uranium ores mines in Lermontov region. 19,6% of OJSC GMP and 16,4% of LLC EMP employees showed an increased level of total IgE in the blood serum. No correlation between the increased total IgE and the presence of allergic deseases was established. These results can be explained by the weakening of the T-suppressor inhibitory mechanism that promotes IgE synthesis in response to antigenic stimulation (allergens, chemical factors, etc.).

ATOPIC DISEASES WITHOUT SYSTEMIC SENSIBILIZATION

The diagnosis of allergic disease related to the group of immediate hypersensitivity involves confirmation of IgE sensitization: positive skin tests with the suspected allergen and/or detection of allergen-specific IgE. Research over the past decades showed that IgE synthesis may occur exclusively in the tissues of the affected organ and derived allergen-specific antibodies may not enter the systemic circulation. In contrast to «atopy», this concept of local sensitization was termed «entopy». local production of IgE was detected in more then 47% of adults previously diagnosed as having non-allergic rhinitis. besides the nasal mucosa, local sensitization was found in lymphoid tissues of nasopharyngeal ring, bronchial mucosa in some patients with non-atopic asthma, esophageal mucosa in patients with eosinophilic esophagitis. The processes of local immune response is currently studied and probably one day the accumulated data will swing our understanding of atopic sensitization, that will be reflected in classification and therapeutic approaches.