Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils

Medical Division, Zieglerspital, Bern, Switzerland.
Clinical & Experimental Allergy (Impact Factor: 4.77). 11/1996; 26(10):1112-8. DOI: 10.1046/j.1365-2222.1996.d01-259.x
Source: PubMed


Rapid clinical tolerance can be induced over several hours by very fast bee venom immunotherapy (VIT) protocols.
To investigate the mechanisms underlying VIT we examined the changes of blood basophil responsiveness during VIT.
Seven bee venom allergic patients with a history of severe systemic reactions after a bee sting were investigated. A cumulative dose of 111.1 micrograms bee venom (BV) was administered sc over 3.5 h under intensive care conditions according to an ultra-rush protocol. The release of histamine and the formation of leukotrienes in response to BV, major BV allergen Phospholipase A2 (PLA), IgE receptor cross-linking with the use of monoclonal antibodies against IgE and IgE receptor, as well as IgE independent activation in response to C5a were determined in vitro before and after ultra-rush VIT.
We demonstrated a decrease of total histamine in peripheral blood leucocytes just after VIT. Histamine release in response to all the stimuli used is not affected by ultra-rush VIT, if expressed as per cent release of total histamine. However, the absolute amount product released in response to stimulation was decreased, particularly with allergen (BV, PLA). We also found a significant reduction of LTC4 formation after VIT in samples stimulated with specific allergen (BV, PLA).
Blood basophils are a target for VIT, which induces impaired release of both preformed and newly generated mediators. However, we believe the basic mechanisms of rapid clinical tolerance induced by ultra-rush VIT remain to be investigated.

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    • "Since no association was found between the frequency of PB basophils and therapy, this seems to indicate, that the beneficial effects of SCIT on histamine-related symptoms could be due not to a variation in the number of circulating basophils but as a result of histamine lower production. In line with this, previous studies have also reported increased expression of histidine decarboxylase in AR patients nasal mucosa, a key enzyme for the production of histamine [46], and a decreased histamine release as a result of specific immunotherapy to hymenoptera venom [47]. A relevant finding in our study was a negative correlation between time under SCIT and HNMT gene expression and since the immunotherapy could modify the histamine metabolism, the decrease of HNMT gene expression seems to be an effect of SCIT. "
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    ABSTRACT: Background Basophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E – mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known. Methods Peripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/β1 (TPSAB1) gene expression was assessed by real-time PCR. Results Higher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4. Conclusion PB basophils from patients with AR show altered functional features, which seems to be influenced by SCIT, suggesting that these cells could be useful to clarify the SCIT triggered mechanisms at a systemic level.
    Allergy Asthma and Clinical Immunology 10/2013; 9(1). DOI:10.1186/1710-1492-9-40 · 2.03 Impact Factor
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    • "Besides this, in systemic allergen imunotherapy allergens cause cytokine shift with a significant decrease in the level of allergen specific IgE and T cell responses to the allergen (King et al., 1976) and provided protection to the patients (Julet et al., 1996). It contributes to decrease mast cells or eosinophil activation, which might be improve after re-exposure of allergen (Simons et al., 1996). "
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    ABSTRACT: Insect venom is a poisonous substance that contains a complex mixture of certain proteins, enzymes, small peptides, certain inorganic elements and acids. These venom components are responsible for multiple pharmacological effects in different organisms and act like toxins. These act at cellular level and break the normal barrier to leak out molecules across the cell membrane and forms ion channels by attaching themselves to the membrane surface. Venom allergens cause immuno-stimulation of body tissues and show strong T cell responses in hypersensitive patients and signify the production of allergen specific IgE antibodies and generate anaphylactic reactions.. These also trigger a cascade of mediators including histamine, leucotrienes, and platelet activating factors, enzymes and peptides. Venom toxins make fast release of certain chemicals i.e. serotonin, kinins, postaglandins and leukotrienes that results in visible clinical symptoms related to paralysis, inflammation, swelling and itching. Insect venom toxins elevate the level of blood sugar, lactate, glucagon and cortisol and cause massive destruction of RBCs and nerve cells. Besides this, insect venom possess highly potent short peptides, which act upon ion channels of excitable cells and inhibit the activity of important metabolic enzymes like ACP ALP, GPT, GOT, LDH, AChE and Creatinine phosphokinase. Melittin is a short peptide that shows cytotoxicity and cause intra-vascular hemolysis of RBCs, lecocytes, platelets and vascular endothelium. It is highly basic and inserts itself into the phospholipid bi-layer of cell membranes. It in conjugation with PLA2 causes active pancreatitis and rhabdomyolysis in patients. Indeed, it appears that peptide toxins are strong ion channel blockers, which selectively act on various ion channels. This review aims to emphasize use of toxin specific immunoglobulin in for immunotherapy of patients to detoxify the effect of venom toxins. Immunotherapy contributes to decrease the number of mast cells, do activation of eosinophils, and induce T cell tolerance to the venom allergen. It subside the toxic effects of venom toxins and much ably revert the enzyme activity
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    • "It has been demonstrated that an absolute amount of histamine released in response to stimulation was decreased after major bee venom allergen stimulations. Moreover, a significant reduction in leukotriene C4 production after VIT in samples stimulated with that specific allergen was reported [19]. Additionally, suppression of basophil IL-4 and IL-13 during early phases of rush immunotherapy has been demonstrated [20,21]. "
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    ABSTRACT: : Allergen-specific immunotherapy (SIT) is the cornerstone of the management of allergic diseases, which targets modification of the immunologic response, along with environmental allergen avoidance and pharmacotherapy. SIT is associated with improved tolerance to allergen challenge, with a decrease in immediate-phase and late-phase allergic inflammation. SIT has the potential to prevent development of new sensitizations and progression of allergic rhinitis to asthma. It has a role in cellular and humoral responses in a modified pattern. The ratio of T helper (Th)1 cytokines to Th2 cytokines is increased following SIT, and functional regulatory T cells are induced. Interleukin-10 production by monocytes, macrophages, and B and T cells is increased, as well as expression of transforming growth factor beta. SIT is associated with increases in allergen-specific antibodies in IgA, IgG1, and IgG4 isotypes. These blocking-type immunoglobulins, particularly IgG4, may compete with IgE binding to allergen, decreasing the allergen presentation with the high- and low-affinity receptors for IgE (FcepsilonRI and FcepsilonRII, respectively). Additionally, SIT reduces the number of mast cells and eosinophils in the target tissues and release of mediators from these cells.
    Allergy Asthma and Clinical Immunology 09/2008; 4(3):106-10. DOI:10.1186/1710-1492-4-3-106 · 2.03 Impact Factor
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