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

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.