[Cross-reactivity to honeybee and wasp venom]

About 30-40% of patients with insect venom allergy have IgE antibodies reacting with both honeybee and Vespula venom. Apart from true double sensitization, IgE against cross-reactive carbohydrate determinants (CCDs, alpha1,3-fucosylated N-glycans) with low clinical relevance is the most frequent and often only cause for the multiple reactivity. Venom hyaluronidases have been identified as the most important allergens displaying CCDs, whereas cross-reactions through the hyaluronidases' peptide backbones are less common. If IgE binding to CCDs is disregarded, Vespula venom hyaluronidase is only a minor allergen. In-vitro tests using fucosylated plant glycoproteins (e.g. assessment of specific IgE antibodies by CAP-FEiA to bromelain) are helpful in identifying sera containing CCD-specific IgE, although a positive result (occurring in 70-80% of all double-positive sera) does not reliably exclude true double-sensitization. Reciprocal in-vitro inhibition including non-venom inhibitor proteins rich in CCDs is the method of choice to discriminate between double-sensitization and cross-reactivity. Future in-vitro diagnosis will be markedly improved when recombinant allergens lacking CCDs become commercially available.