Background Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to ...the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. Objective We performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens. Methods Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. Results IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen–specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3– and Api m 10–specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. Conclusion Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations.
Background Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which ...have been reported to be underrepresented in therapeutic HBV preparations. Objective We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome. Methods HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge. Results No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable. Conclusions Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy.
Because a similar sIgE/tIgE discordance has already been reported for 5 different allergens (Bet v 1, Can f 1, Der p 2, Fel d 1, and Gal d 1),5-7 it is likely to apply also to the Hymenoptera venom ...allergens discussed here and explain the seemingly more sensitive detection of sIgE to rApi m 1 and rVes v 5 reported by Schrautzer et al.1 In line with this is the observation by Selb et al2 that positive values of rApi m 1 and rVes v 5 were, on average, 2.7 and 2.3 times higher with the Immulite than with the ImmunoCAP system.2 Unfortunately, Schrautzer et al1 did not provide data on the actual sIgE levels obtained, preventing a corresponding evaluation of their results.
To the Editor: Epidemiologic studies indicate that 0.05% to 2% of the European and North American population develop systemic reactions after stings from honeybee or yellow jacket species.1 The ...diagnosis of Hymenoptera venom allergy is based on a combination of a clinical history of anaphylaxis to Hymenoptera sting, positive skin test response, and specific IgE (sIgE) antibodies. Because of the insufficient specificity and sensitivity of intradermal skin testing, ranging, respectively, between 54% and 100% and 26% and 89% depending on extracts and concentrations used, the measurement of sIgE against native extracts of Hymenoptera is an additional but not substitutive in vitro test.2 Thus, the group of patients with a clinical history of anaphylaxis but negative sIgE measurement against commercial venom extracts represents a major diagnostic challenge.
...the low frequency of sensitization to recombinant (r) Api m 1 compared with the bee venom extract is a cause for concern. By contrast, IgE determination reveals double-positive results in up to ...59% of patients.2 Thus, a diagnostic tool is urgently needed to exclude cross-reactivity via cross-reactive carbohydrate determinants. Because wasp venom allergies are more frequent, and bee venom bears more cross-reactive carbohydrate determinants, typically nonspecific cross-reactions to bee venom must be excluded.
...our data suggest that IgE binding to nApi m 1 and rApi m 1 (i208) is comparable in CCD-negative patients with BV allergy and that only a minority of patients displaying low levels of IgE to ...nApi m 1 might not be detected by rApi m 1.
...while recombinant Hymenoptera venom allergens play an important role in the differentiation between genuine sensitization to and cross-reactivity between honeybee and vespid venoms,5-7 they ...provide no significant improvement over current venom extract tests in their ability to detect Hymenoptera venom-allergic patients.
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