Hymenoptera venom immunotherapy (original) (raw)
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Specific immunotherapy with hymenoptera venom
Clinical and Applied Immunology Reviews, 2001
Venom immunotherapy (VIT) is an effective treatment for most subjects who are allergic to hymenoptera venom. We have studied 22 patients (16 honey bee venom allergic and 6 vespula sp. venom allergic) subjected to immunotherapy with aqueous extract of pure venom from Allbay, Dome-Hollister-Stier. In one group of 12 patients, VIT was performed according to a rush protocol and we measured specific IgE and IgG4 during a 4-year follow-up period. We observed a decrease in specific IgE and an increase in specific IgG4 in all patients. In order to determine the safety of ultra-rush protocols (3.5 h) we have recently selected one other group of 10 patients in whom we measured tryptase release during the 24 h (at 2, 3, 4, 6, 8, 10, 12 and 24 h) after the beginning of the ultra-rush schedule. We observed no increase in adverse reactions during the induction or maintenance phase relative to rush protocols. Regarding tryptase levels, we observed no significant differences between basal and the several measurements performed during the ultra-rush VIT schedule. These results suggest that an increase in specific IgG4 is correlated with the protective effect of immunotherapy and that ultra-rush VIT is not associated with significant mast cell activation. Ultra-rush protocols are clinically safe, with a rate of systemic reactions similar to rush protocols and with less local reactions. There is no evidence of ultra-rush VIT induced mast-cell degranulation, and serum tryptase levels have not shown significant variations during ultra-rush VIT.
Time-dependent effect of desensitization with wasp venom on selected parameters of the immune system
Scientific Reports
The emergence of tolerance during Hymenoptera venom immunotherapy (VIT) is a complex process. The main goal of VIT is to induce a change from proinflammatory Th2 response to the Th1 response. However, the immune mechanism of acquiring rapid tolerance during VIT has not yet been fully understood. Therefore, we have analyzed (in 4-time points: 0, 2, 6, and 24 weeks after the initiation phase of VIT) the concentration of complement C3, C4, and C5 components, lymphocyte subpopulations (flow cytometry), as well as histamine and tryptase serum concentrations of 43 patients with wasp venom allergy (III and IV Müller grade) classified to ultra-rush treatment and 18 volunteers as the control group (CG). We observed that VIT affected the immune system by inducing changes in the complement system (decreased C3 and C4 compartment protein concentrations) and "normalized" the percentage of lymphocytes and neutrophils in the peripheral blood. Moreover, a significant increase in the perce...
Clinical & Experimental Allergy, 1993
This paper investigates the relationship between venom IgG levels and protection from stings. Venom-specific IgG antibody levels have been measured by radioimmunoassay in untreated wasp-(« = 38) and bee-allergic (n= 16) patients presenting with systemic reactions to stings and in a sub-group of these (wasp= 15; bee = 9), before and after the initial course of venom immunotherapy (VIT). A history was taken of all reactions, the last systemic reaction being graded on a scale of 1-8 and ofthe number and timing of stings. In untreated patients venom IgG levels were much higher in bee-allergic patients (mean ± s.e, = 68 2 ± 7-1 % positive pool) than in the wasp group (27-1 ± 4 2%) {P< 0-05 Mann-Whitney U-test). There was a marked rise in venom IgG after the initial course of VIT in the wasp group (geometric mean and 95% confidence intervals = 40 5%, 28-8-54 3) but a mueh smaller rise in the bee group (15 3%, 6-6-241), with no overlap in the 95% confidence intervals. Bee patients, who were mainly beekeepers or their relatives, had been more heavily immunized with venom than wasp patients. They had received: (i) more stings (mean number of stings: bee, 26; wasp, 4; P < 0001) and (ii) more stings per year. Wasp patients received their smaller number of stings over a much longer period, up to 40 yr. There was no correlation between the severity of the last systemic reaction and the venom IgG levels alone or venom IgG and IgE levels in combined analysis in either bee or wasp patients. This study shows that the pattern of IgG response differs in bee and wasp-allergic subjects, and that most bee-allergic subjects with systemic reactions have high levels of venom IgG. The degree of immunization with venom seems to be an important determinant of the venom IgG level. Our findings suggest that venom-specific IgG levels do not predict systemic reactions to stings and are not useful for monitoring VIT. If protection from stings is IgG-mediated, our observations suggest that the relevant immune response is more complex, possibly involving IgG sub-elasses, IgG antibodies to individual venom antigens or antibody affinity, and not adequately reflected by measurement of the concentration of venom-specific IgG.
Clinical & Experimental Allergy, 2009
Background Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen-IgE complexes to B cells. As this 'functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal. Methods Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age-and gendermatched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay. Results Sera obtained during VIT significantly inhibited allergen-IgE binding to B-cells (pre-treatment = 104AE23%; 2 years = 46AE15%; Po0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment = 8.6AE2.3 AU; 2 years = 26.7AE3.5 AU; Po0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44AE7 AU) in sera obtained after 2 years of VIT (25AE5 AU; Po0.01) and 2 years following the withdrawal of VIT (10AE3 AU; Po0.05). Conclusions In contrast to grass pollen immunotherapy, the persistent decline in venomspecific IgE levels, rather than serum inhibitory activity for FAB, may be more relevant for long-term clinical efficacy of VIT.
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1998
Background Venom immunotherapy (VIT) has proven to be safe and effective in wasp venom anaphylaxis. However, there are no good parameters to indicate when to stop venom immunotherapy. Objective To evaluate the relationship of the lymphocyte transformation test (LTT) to history and specific IgE determination, and to address the time course of lymphocyte transformation responses to wasp (Vespula) venom during VIT and the possible utility of LTT to determine the duration of therapy. Methods Peripheral blood mononuclear cells (PBMCs) of 18 individuals with a history of wasp sting anaphylaxis and a positive serum-venom-specific IgE, were stimulated with wasp venom before immunotherapy, at the end of a 5-day semi-rush immunotherapy and at 24 months during venom immunotherapy. Results, expressed as stimulation index (SI), were compared with the SI in seven asymptomatic stung controls. Results In controls the median (minimum-maximum) of the SI were 2.39 (0.52-3.39) before therapy and 2.39 (1.12-6.02) when repeated after 24 months. For patients the median (minimum-maximum) of the SI were 10.13 (1.19-44.88) before immunotherapy (d0), 2.73 (0.67-12.03) at the end of the build-up immunotherapy (d5) and 4.21 (0.88-14.66) at the end of 24 months of maintenance therapy (m24). The proliferation responses in vespidallergic patients were significantly higher than in stung controls (P ¼ 0.006) but only13/18 patients showed a positive LTT result before the start of immunotherapy (sensitivity of the LTT 72%). When the LTT was repeated after a 5 day build-up hyposensitization course the SI significantly dropped as compared to the pre-treatment levels (P ¼ 0.002). The SI of the LTT was negative in eight out of 18 patients at 24 months and the median values were significantly lower than before therapy (P ¼ 0.03). Conclusions Although, in the absence of sting challenge data it is not possible to draw conclusions about the predictive value of the LTT, our data may suggest that abolition of the LTT during VIT might indicate clinical insensitivity. Further studies, comparing the results of sting challenges, with the results of lymphocyte transformation will be necessary in order to evaluate the role of LTT in stopping immunotherapy.
EAACI Guidelines on Allergen Immunotherapy: Hymenoptera venom allergy
Allergy, 2017
Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid or ant sting. Systemic allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate-to-severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using t...
IgE and T-cell responses to high-molecular weight allergens from bee venom
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1999
Background Bee venom contains multiple allergens with a wide distribution of molecular weight. In contrast with conventional bee venom desensitization, peptide or recombinant allergen immunotherapy may have to take into account patients' individual patterns of humoral or cellular response. Objective To study immunoglobulin (Ig)E and T-cell responses to high-molecular weight bee venom allergens Ն 50 kDa. Methods Bee venom proteins were separated by size exclusion chromatography and fractions were characterized by one and two-dimensional gel electrophoresis. IgE antibody binding to bee venom fractions was analysed by immunoblotting and T-cell responses by proliferation assay. Results Among 38 bee venom-hypersensitive patients, IgE recognition pattern of bee venom allergens varied greatly. IgE bound mainly to phospholipase A 2 and furthermore to several proteins Ն 50 kDa (50, 54, 69, 84 and 94 kDa). N-terminal sequences of these proteins showed no homology with known proteins. In addition, peripheral mononuclear cells from patients as well as from nonatopic donors strongly proliferated in response to those proteins. Conclusions Although present in low amounts, high-molecular weight allergens from bee venom elicit strong IgE and T-cell responses, and may need to be considered as clinically relevant. Therefore, the development of peptide or recombinant protein-based immunotherapy for bee venom allergy may require careful characterization of such allergens.
A Cutaneous Allergen Neutralisation Test That Correlates with the Duration of Venom Immunotherapy
International Archives of Allergy and Immunology, 2006
Specific IgE antibodies against Hymenoptera venom can be determined in a large proportion of the general population. The sting allergy typically manifests with local reactions in 10-15% [1] and systemic anaphylactic sting reactions in 0.3-7.5% [2, 3] of the same population, whereby the prevalence is typically lower for children than for adults. Among beekeepers, anaphylaxis can occur in as much as 14-43% of the patients . The annual mortality associated with Hymenoptera venom allergy is estimated between 0.03 and 0.48 per million . The majority of fatalities occur in the elderly with cardiovascular diseases or those being treated with  -receptor blocking agents . Patients suffering from systemic reactions after Hymenoptera stings should be evaluated allergologically, including skin tests and determination of venomspecific IgE in the serum.