Basophil Activation Test in Double-Sensitized Patients With Hymenoptera Venom Allergy: Additional Benefit of Component-Resolved Diagnostics.

BACKGROUND: In Hymenoptera venom allergy serologically double-sensitized patients, it is often difficult to identify the culprit insect for venom immunotherapy (VIT). OBJECTIVES: To evaluate if basophil activation tests (BATs) performed not only with venom extracts but additionally with single component-resolved diagnostics could differentiate between sensitized and allergic individuals and how the test results influenced the physicians' decision regarding VIT. METHODS: BATs were performed with bee and wasp venom extracts and with single components (Api m 1, Api m 10, Ves v 1, and Ves v 5) in 31 serologically double-sensitized patients. RESULTS: In 28 finally included individuals, 9 BATs were positive and 4 negative for both venoms. Fourteen of 28 BATs showed positive results for wasp venom alone. Two of 10 BATs positive for bee venom were only positive to Api m 1 and 1 of 28 BATs only to Api m 10, but not for whole bee venom extract. Five of 23 BATs positive for wasp venom were only positive for Ves v 5 but negative for wasp venom extract and Ves v 1. Finally, VIT with both insect venoms was recommended in 4 of 28 individuals, with wasp venom alone in 21 of 28 patients and with bee venom alone in 1 of 28. In 2 cases no VIT was recommended. CONCLUSIONS: BATs with Ves v 5, followed by Api m 1 and Api m 10, were helpful for the decision for VIT with the clinically relevant insect in 8 of 28 (28.6%) patients. A BAT with components should therefore be additionally carried out in cases with equivocal results.

Evolution of Api m10 Specific IgE and IgG4 After One Year of Bee Venom Immunotherapy.

Summary: Background. Bee-venom (BV) anaphylaxis can be life-threatening, requiring treatment with BV immunotherapy (bVIT). Different molecular profiles may be associated with different outcomes after bVIT. Methods. In 19 patients with BV anaphylaxis, sensitized both to Api m1 and Api m10, we evaluated sIgE and sIgG4 Api m1 and Api m10 levels before and after 1 year bVIT.Results.7 patients (37%) had higher baseline Api m10 than Api m1 sIgE levels (Api m10 predominant). bVIT reduced sIgE to both components but sIgG4 levels were increased only for Api m1. 5 patients (2 in the Api m10 predominant group) were re-stung without anaphylaxis. Conclusions. Although there was no increase in Api m10 sIgG4 levels after 1 year bVIT, we did not observe relevant differences in other outcomes between patients with predominant Api m1 or Api m10 sensitization.

Development of a skin-friendly microemulsion for dermal allergen-specific immunotherapy.

Due to their role in immune responses, the skin dendritic cells (i.e. epidermal Langerhans cells and dermal dendritic cells) have become of great interest to researchers in the past decades. A dermal administration of allergens could target these professional antigen-presenting cells directly and build up immunotolerance. Additionally, many of the adverse side effects, which are seen in the current state of the art specific immunotherapy routes, could be avoided. Therefore, in this study a penetration enhancing microemulsion was developed and its physicochemical properties were determined under several storage conditions. The influence of different preservatives on the microemulsion stability was observed. We examined epidermal penetration of Alexa Fluor-647 labelled bee-venom phospholipase A2 (Api m 1) using the Franz diffusion cell set up and confocal laser-scanning microscopy. First results of an in-vivo Api m 1-allergic mouse model indicated the protective efficacy of dermal AIT with our newly developed microemulsion. Summarily, the developed microemulsion is a suitable, stable drug delivery system for the topical administration of proteogenic allergens into the epidermis and is able to reach dendritic cells in the skin.

rApi m 3 and rApi m 10 improve detection of honey bee sensitization in Hymenoptera venom-allergic patients with double sensitization to honey bee and yellow jacket venom.

Recombinant allergens improve the diagnostic precision in Hymenoptera venom allergy (HVA), in particular in patients with double sensitization to both honey bee (HBV) and yellow jacket venom (YJV). While currently available vespid allergens allow the detection of >95% of YJV-allergic patients, the sensitization frequency to the only available HBV marker allergen rApi m 1 in HBV-allergic patients is lower. Here, we demonstrate that sIgE to additional HBV marker allergens rApi m 3 and rApi m 10 allows the detection of genuine HBV sensitization in 46-65% of Api m 1 negative sera. This is of particular relevance in patients with double sensitization to HBV and YJV that did not identify the culprit insect. Addition of sIgE to rApi m 3 and rApi m 10 provides evidence of HBV sensitization in a large proportion of rApi m 1-negative patients and thus provides a diagnostic marker and rationale for VIT treatment with HBV, which otherwise would have been missing.