Search

Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201.

Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species’ sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom—immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)—were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20–40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.