Application of recombinant antigen 5 allergens from seven allergy-relevant Hymenoptera species in diagnostics

Allergy. 2017 Jan;72(1):98-108. doi: 10.1111/all.13000. Epub 2016 Aug 26.

Abstract

Background: Hymenoptera stings can cause severe anaphylaxis in untreated venom-allergic patients. A correct diagnosis regarding the relevant species for immunotherapy is often hampered by clinically irrelevant cross-reactivity. In vespid venom allergy, cross-reactivity between venoms of different species can be a diagnostic challenge. To address immunological IgE cross-reactivity on molecular level, seven recombinant antigens 5 of the most important Vespoidea groups were assessed by different diagnostic setups.

Methods: The antigens 5 of yellow jackets, hornets, European and American paper wasps, fire ants, white-faced hornets, and Polybia wasps were recombinantly produced in insect cells, immunologically and structurally characterized, and their sIgE reactivity assessed by ImmunoCAP, ELISA, cross-inhibition, and basophil activation test (BAT) in patients with yellow jacket or Polistes venom allergy of two European geographical areas.

Results: All recombinant allergens were correctly folded and structural models and patient reactivity profiles suggested the presence of conserved and unique B-cell epitopes. All antigens 5 showed extensive cross-reactivity in sIgE analyses, inhibition assays, and BAT. This cross-reactivity was more pronounced in ImmunoCAP measurements with venom extracts than in sIgE analyses with recombinant antigens 5. Dose-response curves with the allergens in BAT allowed a differentiated individual dissection of relevant sensitization.

Conclusions: Due to extensive cross-reactivity in various diagnostic settings, antigens 5 are inappropriate markers for differential sIgE diagnostics in vespid venom allergy. However, the newly available antigens 5 from further vespid species and the combination of recombinant allergen-based sIgE measurements with BAT represents a practicable way to diagnose clinically relevant sensitization in vespid venom allergy.

Keywords: Hymenoptera venom allergy; antigen 5; basophil activation test; cross-reactivity; in vitro sIgE testing.

MeSH terms

  • Allergens / chemistry
  • Allergens / genetics
  • Allergens / immunology*
  • Anaphylaxis / diagnosis*
  • Anaphylaxis / immunology*
  • Animals
  • Arthropod Venoms / chemistry
  • Arthropod Venoms / genetics
  • Arthropod Venoms / immunology*
  • Basophils / immunology
  • Basophils / metabolism
  • Cross Reactions / immunology
  • Humans
  • Hymenoptera / immunology*
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Insect Bites and Stings
  • Models, Molecular
  • Protein Conformation
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology*

Substances

  • Allergens
  • Arthropod Venoms
  • Recombinant Proteins
  • Immunoglobulin E