Hymenoptera venom allergy
Apis mellifera or honeybee venom (HBV) is the best-characterized Hymenoptera venom due to the outstanding importance of this species as elicitor of venom allergy worldwide. Detailed genomic information and proteomic data of the pure venom is available8081-83. So far 12 allergens of HBV are identified84. Only two of them present substantial amounts in the venom, the major allergen phospholipase A2 (Api m 1)(12%) and the minor peptidic allergen melittin (Api m 4)(50%)85. Despite their lower abundance in HBV compared to Api m 1, a role as relevant major allergen was also confirmed for Api m 2 (hyaluronidase), Api m 3 (acid phosphatase), Api m 5 (dipeptidylpeptidase IV) and Api m 10 (icarapin) with sIgE reactivity in the range of 47.9-52.2%, 49.6-50%, 58.3-61.7% and 61.8-72.2% of allergic patients’ sera, respectively86,87. For the other HBV allergens less information about sensitization rates is available 88-90. Some HBV allergens have been identified as risk markers of more severe clinical phenotypes such as Api m 4 or of venom immunotherapy (VIT) failure such as Api m 1086,91.
Prominent Vespula spp. (known as yellow jackets in the USA) allergens include phospholipase A1 (Ves v 1), hyaluronidase (Ves v 2.0101) and antigen 5 (Ves v 5)92,93. A second hyaluronidase (Ves v 2.0201), carrying an inactivation mutation in the active site of the enzyme, was identified, which seems to be the predominant isoform94,95. Yellow-jacket venom (YJV) also contains a dipeptidylpeptidase IV (Ves v 3) which shows high homology to HBV Api m 596. The sensitization rates of YJV-allergic patients to Ves v 1, Ves v 3 and Ves v 5 are 33.3-54% 97-102, 50-62.8%96,97and 84.5-100%, respectively97,99,100,102-104. In contrast to HBV hyaluronidase Api m 2, which is a major allergen, the YJV homologue Ves v 2 seems to be of restricted relevance and sensitization was reported in 5-25% of YJV-allergic patients105.
The allergen composition of Polistes dominula venom (PDV) is very similar to that of YJV and the most important allergens are phospholipase A1 (Pol d 1), dipeptidylpeptidase IV (Pol d 3) and antigen 5 (Pol d 5) with sensitization rates of 87%106, 66.7%107 and 69-72%106, respectively.
CRD is helpful to discriminate between genuine double sensitization and cross-reactivity, allowing physicians to optimize patient selection for VIT. The potential of CRD becomes evident by the fact that HBV and YJV in addition to homologous allergens also contain differentiating marker allergens that are present in either HBV or YJV. This is not the case when differential diagnosis between Vespula spp . andPolistes spp . is required (Figure 6). CRD is also helpful in identifying patients with Hymenoptera venom-induced anaphylaxis having negative test results to whole venom extracts, as it can be the case in hymenoptera venom-allergic patients with mast cell disorders108. Currently available allergens of honeybee and vespid venoms (see Table 2) allow a molecular diagnosis in the vast majority of patients, but not in 100% of them. Moreover, not all allergens are available for one assay system. New recombinant molecules are needed to improve the diagnosis ofPolistes spp .-allergic patients, especially in the case of double-positivity to both Polistes spp . and Vespula spp . venom, in order to prevent unnecessary double VIT (Figure 7A). Although diagnostic sensitivity of the currently available allergen panel, particularly of HBV, is not 100%, CRD has clearly improved discrimination of primary allergy and cross-reactivity in YJV and HBV allergy, thus facilitating correct prescription of VIT. A suggested diagnostic algorithm to discriminate between HBV and YJV allergy using CRD is given in Figure 7B. Of note, the same algorithm using the corresponding PDV allergens can also be applied to discriminate between HBV and PDV allergy.