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The increased incidence of allergic diseases and food-induced anaphylaxis overtime demands an urgent development of disease-modifying therapies that reverse the synthesis of IgE and the induction of IgE-mediated allergic reactions. Keywords: allergic sensitization; food allergens; germinal center; IgE synthesis EN allergic sensitization food allergens germinal center IgE synthesis 1545 1549 5 05/17/21 20210501 NES 210501 Understanding the biology of IgE in humans has become a matter of interest that remains incompletely understood due to the rarity of peripheral IgE SP + sp cells. Biology of IgE production: IgE cell differentiation and the memory of IgE responses. [Extracted from the article]

Background The production of allergen-specific IgE antibodies is a hallmark of IgE-mediated allergy but the contribution of blood cells to allergen-specific IgE production in allergic patients has not been studied in detail. Objective Aim of this study was the characterization of IgE-producing cells in the blood of allergic patients and the determination of the amount of IgE antibodies which are produced by these cells in relation to total amounts of circulating specific IgE. Methods Peripheral blood mononuclear cells ( PBMCs) were isolated from allergic patients and cell populations were purified or depleted using magnetically labelled antibodies directed against specific cell surface markers ( CD19, CD20, CD22, CD27, CD38, CD126, CD138, CD203c). Allergen-specific IgE was measured in serum samples and cell culture supernatants by quantitative Immuno CAP measurements and by ELISA using purified recombinant allergens. IgE transcripts were detected using RT- PCR with primers specific for human IgE. Results We found that allergen-specific IgE levels in PBMC supernatants correlated strongly with specific serum IgE but represented less than 1% of circulating IgE. Depletion of basophils resulted in substantial reduction of allergen-specific IgE levels in PBMC culture supernatants suggesting that an important source of allergen-specific IgE in PBMC supernatants could be IgE derived from the surface of basophils. Newly synthesized IgE was derived from CD138+ plasma cells, but not from B and B memory cells, and accounted for only approximately 0.2% of circulating IgE in blood. Conclusion and Clinical Relevance Our finding that the majority of allergen-specific IgE in the peripheral blood is not derived from IgE-secreting cells in the blood suggests local IgE production in tissues as a major source for allergen-specific IgE and possible target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Summary Background Kimura's disease (KD) is a chronic inflammatory disorder characterized by tumours in the head and neck region, enlarged lymph nodes, increased eosinophil counts and high serum IgE. Mast cells are known to play a central role in IgE-mediated allergic diseases through the release of inflammatory mediators like IL-4, IL-5 and chemokines. We hypothesized that mast cells may play a role in the pathogenesis of KD by regulating eosinophilic infiltration and IgE synthesis. Objective In order to investigate the role of mast cells in the pathogenesis of KD, we examined the expression of cytokines/chemokines in the lesions of KD. Methods We examined the number of tryptase+ cells, EG2+ cells, CD3+ cells, IL-4+ cells, IL-5+ cells, eotaxin+ cells, RANTES+ cells and CCR3+ cells in five specimens of KD versus normal tissues by immunohistochemistry. The sources of IL-4, IL-5, eotaxin and RANTES and the expression of CCR3 were examined by immunostaining of serial sections with antibodies to IL-4, IL-5, eotaxin, RANTES and CCR3, and antibodies to tryptase, ECP (EG2) and CD3. Results Mast cells, activated eosinophils, T cells, IL-4+ cells, IL-5+ cells, eotaxin+ cells, RANTES+ cells and CCR3+ cells were all increased in the lesions of KD as compared with those in normal tissue. Mast cells and T cells were the major source of IL-4, whereas mast cells, T cells and activated eosinophils were the main source of IL-5. Mast cells, T cells and activated eosinophils were the main source of eotaxin and RANTES. Conclusions The number of IL-4, IL-5, eotaxin and RANTES-expressing mast cells and T cells were increased in the lesions of KD. As mast cells are lesional resident cells, these cells may play an important role in the pathogenesis of KD by regulating IgE synthesis and orchestrating eosinophilic infiltration. [ABSTRACT FROM AUTHOR]

Corticotropin releasing factor, adrenocorticotropic hormone (ACTH) and alpha-melanocyte stimulating hormone either inhibit or enhance in a dose-dependent fashion an interleukin-4 (IL-4) driven human IgE synthesis in vitro. Here, we show that culture conditions strongly influence the earlier observed dose- and donor-dependent effects of adrenocorticotropic hormone. The effect of ACTH on IgE synthesis became only apparent late during culture periods, suggesting an indirect effect via the cellular microenvironment rather than by acting directly at the level of B-cell isotype switching. Thus, we studied other proopiomelanocortin (POMC) derived peptides and neuropeptides known to influence the cellular microenvironment. Indeed, similar modulatory effects on IgE synthesis were also observed by the addition of other proopiomelanocortin-derived peptides such as α-, β-, and γ-endorphins as well as by the opioid binding pentapeptide Leu-enkephalin. Furthermore the neuropeptide substance P accentuated an IL-4 or an IL-4 and anti-CD40 antibody driven class switch to IgE. In contrast to ACTH, substance P interfered not only with IgE synthesis but also with the synthesis of the other immunoglobulin isotypes. Thus, systemically acting neuroendocrine peptides such as ACTH and locally acting neuropeptides such as the enkephalins and substance P can modulate the magnitude of an IL-4 induced lgE response. [ABSTRACT FROM AUTHOR]

Recently, hydrocortisone (HC) has been shown significantly to enhance interleukin-4 (IL-4)-induced in vitro IgE synthesis. For investigation of possible effects of synthetic corticosteroids hut also of effects of other important human hormones, peripheral blood mononuclear cells (PBMC) were incubated with IL-4 and various concentrations of the hormones IgE secreted in the supernatant was determined after a 14-d culture period. Like HC, all synthetic corticosteroids potentiated IgE secretion A minor effect was noted for the mineralocorticoid aldosterone. No modulating effect on IL-4-induced IgE formation was observed for adrenocorticotropic hormone (ACTH), somatotropin (STH), thyroid-stimulating hormone (TSH), triiodothyronine, thyroxine, epinephrine, noradrenaline, insulin, and glucagon. [ABSTRACT FROM AUTHOR]

The effects of indomethacin or macrophage-depletion on the in vitro unstimulated and pokeweed mitogen (PWM)-induced synthesis of IgG and IgE were compared. The effect on the unstimulated synthesis of IgG and IgE was similar, namely, no effect due to indomethacin and enhancement due to macrophage depletion. In contrast, the effect on PWM-induced synthesis was dissimilar. Macrophage depletion enhanced IgG but inhibited IgE production. The effect of indomethacin paralleled that of macrophage depletion suggesting the involvement of prostaglandins. It seems that the regulatory effect of macrophages is different in the IgE system compared with the IgG system. [ABSTRACT FROM AUTHOR]

Peripheral blood lymphocytes from patients with atopy were studied for IgE production in vitro. Addition of a beta-receptor blocking agent (propranolol) to lymphocytes from 9 of 10 patients with low spontaneous IgE production in vitro caused increased IgE production. In 10 tests with lymphocytes from patients, who were undergoing hyposensitization treatment for cat epithelium and/or birch pollen allergy, no spontaneous in vitro production of the relevant antigen-specific IgE antibodies was detected. However, when propranolol was added to the lymphocyte cultures in vitro, production of antigen-specific IgE antibodies was found. No such production was found when lymphocytes from patients who were not allergic to either of these antigens were studied, Szentivanyi's theory of a partial blockade of beta-adrenergic receptors in atopy and a possible linkage between this theory and the hypotheses of disturbed regulatory functions in the immune system of patients with atopy is discussed. [ABSTRACT FROM AUTHOR]