Hymenoptera venom immunotherapy.
ABSTRACT Subcutaneous venom immunotherapy is the only effective treatment for patients who experience severe hymenoptera sting-induced allergic reactions, and the treatment also improves health-related quality of life. This article examines advances in various areas of this treatment, which include the immunological mechanisms of early and long-term efficacy, indications and contraindications, selection of venom, treatment protocols, duration, risk factors for systemic reactions in untreated and treated patients as well as for relapse following cessation of treatment. Current and future strategies for improving safety and efficacy are also examined. However, although progress in the past few years has been fruitful, much remains to be accomplished.
SourceAvailable from: Didier Ebo[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Despite the efficiency of venom immunotherapy, the effects on basophils and mast cells remain incompletely understood and probably vary according to the treatment phase. OBJECTIVES: To study the effect of build-up and maintenance venom immunotherapy on individual basophils. METHODS: Intracellular histamine and its release was analyzed flow cytometrically by a new enzyme-affinity method using diamine oxidase conjugated to laser-excitable fluorochromes. Phenotyping of cells included flow cytometric quantification of CD63 and CD203c. Analyses of basophil activation experiments were performed before the start of treatment, after build-up therapy and during maintenance therapy. RESULTS: Before the start of therapy, patients demonstrated significantly higher numbers of basophils when compared with stung control individuals. At the end of build-up therapy a decrease of basophil numbers was observed, whereas during maintenance therapy basophil counts returned to pretreatment values. Before the start of therapy, the intracellular histamine content per cell in patients was significantly higher when compared with stung control individuals. During maintenance therapy intracellular histamine content decreased to values observed in stung control individuals. In addition, maintenance therapy lowered the net release of histamine per cell in response to optimal stimulation with wasp venom. CONCLUSIONS: We introduce a novel technique that enables to assess the effects of venom immunotherapy on basophils. This new technique may help to monitor treatment effects in individual patients and could aid in the development of more efficient and better tolerated immunotherapy protocols. © 2013 International Clinical Cytometry Society.Cytometry Part B Clinical Cytometry 05/2013; 84B(3). DOI:10.1002/cyto.b.21084 · 2.28 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: People suffering from honeybee venom allergy can be treated by venom immunotherapy, which consists in the subcutaneous injection of increasing doses of allergen extracts over a period of 3-5 years. Such a procedure is time-consuming and the risks of severe side reactions are important. Approaches based on the use of novel adjuvants to blunt pro-allergic Th2-type immune responses represent a sound alternative. In this study, we evaluated in a mouse model of honeybee venom allergy the protection induced by the prophylactic use of the major allergen phospholipase A2 (PLA2) associated to microbubbles (MB). Antibody (Ab) and T cell responses, as detected by ELISA and CFSE-based proliferation assays, were first examined after prophylactic immunization of CBA/J mice with PLA2-MB, and second after sensitization with native PLA2. Mice were eventually challenged with a lethal dose of PLA2 to assess protection against anaphylaxis. Prophylactic immunization with PLA2-MB induced PLA2-specific IgG and IgA Ab, triggered the production of IFN-γ and IL-10, and the differentiation of PLA2-specific Foxp3(+) Treg. Immunized/sensitized mice displayed: (1) increased titers of potent blocking IgG1, IgG2a and IgG3 Ab, (2) both reduced allergen-specific T cell proliferation and Th2-type cytokine production and (3) elevated frequencies of specific Foxp3(+) Treg and increased production of TGF-β, as compared to naïve/sensitized animals. Immunomodulation correlated with reduced signs of anaphylaxis after allergen challenge. Our data demonstrate the ability of PLA2-MB to prophylactically protect mice against subsequent sensitization and death-inducing PLA2 challenge for up to 4 months, revealing so far unraveled immunomodulatory properties of MB. These data, combined with the safe use of MB as contrast agents for in situ imaging in humans, render them an immunotherapeutic agent of great interest for further evaluation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Clinical & Experimental Allergy 04/2015; DOI:10.1111/cea.12555 · 4.32 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific.PLoS ONE 04/2014; 9(4):e94762. DOI:10.1371/journal.pone.0094762 · 3.53 Impact Factor