Molecular diagnostics and inhibition of cross‐reactive carbohydrate determinants in Hymenoptera venom allergy

Abstract

Background The composition of venom extracts, cross‐reactive carbohydrate determinants (CCD) and the component‐resolved diagnostics (CRD) are important fields of investigation. IgE‐reactivity to CCD complicates the interpretation of IgE to Hymenoptera venoms, especially in patients with multiple‐positivity. We analyzed the clinical importance of CRD and CCD‐inhibition for selection of allergens for venom immunotherapy (VIT). Methods In 71 patients, we measured specific IgE (sIgE) to honeybee venom (HBV), wasp venom (WV), hornet venom (HV), CCD, and recombinant allergens: phospholipase A2 (rApi m 1), hyaluronidase (rApi m 2), icarapin (rApi m 10), antigen 5 (rVes v 5), and phospholipase A1 (Immunoblot). In 29/71 HBV/WV/HV/CCD‐positive patients CCD‐inhibition was performed. According to CRD and CCD‐inhibition, we identified true sensitization and defined groups of multiple‐positive patients who needed CCD‐inhibition before starting VIT. Results sIgE‐rApi m 1, sIgE‐rApi m 2, and sIgE‐rApi m 10 were detected in 65.7%, 68.4%, and 58%, respectively. In HBV allergic patients, CRD sensitivity was 86.8%. In WV allergic patients, sensitivity of sIgE‐rVes v 5 was 94%. True multiple‐sensitization was found in 44.8% of HBV/WV/HV/CCD‐positive patients after CCD‐inhibition. Patients with multiple venom‐ and CCD‐positivity had more frequent severe allergic reactions (p < 0.001). CCD‐inhibition was helpful in HBV/WV/HV/CCD‐positive patients who were negative to all tested recombinant honeybee allergens. Persistence of HBV‐positivity after CCD‐inhibition requires CRD to other honeybee recombinant allergens. Conclusion CRD, using a profile of five most important recombinant allergens and CCD, has a high sensitivity for the diagnosis of venom allergy, especially in patients positive to several venom extracts. CRD and CCD‐inhibition are helpful to reveal the clinically relevant, true sensitization and improve the selection of venoms for long‐lasting VIT.

Revealing clinically relevant specific IgE sensitization patterns in Hymenoptera venom allergy with dimension reduction and clustering

“…Cross-reactive carbohydrate determinants (CCDs) present in venom extracts can complicate the identification of primary Hymenoptera allergies. To address this, molecular or component-resolved diagnosis (CRD) 17 , 18 enable the production of recombinant allergen proteins free of CCDs. For Hymenoptera venom allergies, CRD isolates specific allergens, including Api m 2, 3, 4, 10, Ves v 1, and Ves v 5, establishing them as markers for primary honey bee or wasp venom allergies.…”