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Basophil Degranulation (basophil + degranulation)
Selected AbstractsFlow cytometry versus histamine release analysis of in vitro basophil degranulation in allergy to Hymenoptera venomCYTOMETRY, Issue 1 2003C. Lambert Abstract Background Flow cytometry (FCM) has been proposed for specific allergy in vitro testing. We investigated its biological significance for allergy to Hymenoptera venoms and compared it with the routinely performed basophil histamine release test (HRT). Methods Blood samples from 26 allergic and 8 nonallergic donors were incubated with venom at serial concentrations. Basophils were analyzed with anti-CD45-PE-Cyanin 5, Anti-IgE-FITC, and Anti-CD63-Phycoerythrine. HRT was measured by radioimmunoassay. Results FCM was as convenient as HRT for measuring basophil reactivity in at least 87% of allergic and 75% of nonallergic subjects. CD63 outer expression was specifically induced in 91% of releaser subjects (86% on HRT) and in 1 of 10 tests in nonallergic donors, or one of six tests (16% on HRT) in allergic patients tested with an irrelevant allergen. Both methods were concordant in 85.7% of the tests. The three discordant patients had low-grade reactions and borderline biological responses on FCM (n = 2) or HRT (n = 1). Conclusions The dynamic, physiologic significance of CD63, the dose,response curve, and dependency on ethylene-diaminetetra acetic acid suggested that both tests reflect the same mechanism. Cytometry Part B (Clin. Cytometry) 52B:13,19, 2003. © 2003 Wiley-Liss, Inc. [source] Helminths, allergic disorders and IgE-mediated immune responses: Where do we stand?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007Klaus Abstract Th2 responses induced by allergens or helminths share many common features. However, allergen-specific IgE can almost always be detected in atopic patients, whereas helminth-specific IgE is often not detectable and anaphylaxis often occurs in atopy but not helminth infections. This may be due to T regulatory responses induced by the helminths or the lack of helminth-specific IgE. Alternatively non-specific IgE induced by the helminths may protect from mast cell or basophil degranulation by saturating IgE binding sites. Both of these mechanisms have been implicated to be involved in helminth-induced protection from allergic responses. An article in the current issue of the European Journal of Immunology describes the generation of an anti- Nippostrongylus brasiliensis -specific IgE antibody which was used to identify a novel N. brasiliensis antigen (Nb-Ag1). The authors demonstrated that Nb-Ag1 specific IgE could only be detected for a short period of time during infection, and that these levels were sufficient to prime mast cells thereby leading to active cutaneous anaphylaxis after the application of Nb-Ag1. This is the first report clearly showing that a low level of helminth-specific IgE, transiently produced, is able to induce mast cell degranulation in the presence of large amounts of polyclonal IgE. See accompanying article: http://dx.doi/10.1002/eji.200737135 [source] Interleukin-2 immediate type hypersensitivity?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 11 2008Peri Caucig Summary Two patients with metastatic malignant melanoma developed immediate type hypersensitivity-like symptoms while being treated with recombinant interleukin-(IL-)2 immunotherapy. Both patients showed positive skin prick tests to IL-2, enhanced basophil degranulation in vitro and responded to anti-histamines, but laboratory investigations suggested an IgE-independent, pseudoallergic mast cell degranulation against IL-2. [source] Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapyALLERGY, Issue 1 2009J. M. Martínez-Gómez Background:, Current s.c. allergen-specific immunotherapy (SIT) leads to amelioration of IgE-mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side-effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side-effects. Methods:, The major cat allergen Fel d 1 was fused to a TAT-derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT-Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat-dander-allergic patients. Results:, MAT-Fel d 1 enhanced induction of Fel d 1-specific IgG2a antibody responses as well as the secretion of IFN-, and IL-2 from T cells. Subcutaneous allergen-specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT-Fel d 1 caused less degranulation of human basophils than native Fel d 1. Conclusion:, MAT-Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT-Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs. [source] Echinococcus multilocularis metacestode extract triggers human basophils to release interleukin-4PARASITE IMMUNOLOGY, Issue 10 2004E. Aumüller SUMMARY Infections with parasitic helminths are associated with a T helper 2 (Th2) immune response and IgE production. The underlying mechanism, however, is only partially understood. Recently we have isolated a protein from extracts of Schistosoma mansoni eggs that triggers human basophils from non-sensitized donors to release interleukin-4 (IL-4), the key cytokine of a Th2 response. We called this protein IPSE (for IL-4-inducing principle from Schistosoma mansoni eggs). Supposing that IPSE-like IL-4-inducing activities might be a general principle shared among different helminth species, we investigated extracts from the cestode E. multilocularis for its effect on human basophils. Our results showed that extracts from metacestodes of E. multilocularis cause basophil degranulation, as well as the secretion of histamine, IL-4 and IL-13, in a dose-dependent manner. IgE stripping and resensitization of basophils indicated that the mechanism of IL-4 induction requires the presence of IgE on the cells. Since analogous properties have been demonstrated earlier for IPSE, we think that S. mansoni and E. multilocularis may induce a Th2 response in their hosts via a related mechanism, namely, by the induction of IL-4 release from basophils. [source] An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype inhibits basophil degranulation through cross-linking of Fc,RI with Fc,RIIbCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2008S. J. Wigginton Summary Background IgE binds to mast cells and basophils via its high-affinity receptor, Fc,RI, and cross-linking of Fc,RI-bound IgE molecules by allergen leads to the release of allergic mediators characteristic of type I hypersensitivity reactions. Previous work has shown that cross-linking of Fc,RI with Fc,RIIb, an ITIM-containing IgG receptor, leads to inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti-idiotype, has broad reactivity with human IgE and as such has the potential to bind simultaneously to Fc,RI-bound IgE, via its Fab regions, and the negative regulatory receptor, Fc,RIIb, via its Fc region. Objective To assess the ability of human 2G10 to inhibit anti-IgE and allergen-driven basophil degranulation through cross-linking of Fc,RI-bound IgE with Fc,RIIb. Methods 2G10 was assessed for its ability to bind to Fc,RIIb on transfected cells and on purified basophils. In the basophil degranulation assay, basophils were purified from peripheral blood of atopic individuals and activated with either anti-IgE or the house dust mite allergen Der p 1, in the presence or absence of human 2G10. Basophil activation was quantified by analysis of CD63 and CD203c expression on the cell surface, and IL-4 expression intracellularly, using flow cytometery. Results Human 2G10 was able to bind to Fc,RIIb on transfected cells and on purified basophils, and induce a dose-dependent inhibition of both anti-IgE and Der p 1-driven degranulation of basophils. Conclusion The inhibition of basophil degranulation by the human IgG1 anti-idiotype 2G10 highlights the therapeutic potential of IgE-reactive IgG antibodies in restoring basophil integrity through recruitment of the inhibitory receptor Fc,RIIb. [source] Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to Fc,RICLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2005A. Purohit Summary Background Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc, receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. Objective To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1,4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n=18). Methods rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc,RI-derived ,-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. Results Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc,RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. Conclusion Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity. [source] | ||||||||||||||||||||||