In vitro diagnosis of Hymenoptera venom allergy and further development of component resolved diagnostics

Abstract

For most people Hymenoptera stings result in transient and bothersome local inflammatory responses characterized by pain, itching, redness and swelling. In contrast, for those presenting an IgE-mediated allergic reaction, a re-sting may cause life-threatening reactions. In such patients, correct diagnosis is an absolute prerequisite for effective management, i.e. venom-specific immunotherapy. Generally, identification of the offending insect involves a detailed history along with quantification of venom-specific IgE antibodies and venom skin tests. Unfortunately, due to uncertainties associated with both tests, correct diagnosis is not always straightforward. This review summarizes the potentials and limitations of the various in vitro tests that are currently being used in the diagnosis of Hymenoptera venom allergy. Particular attention is paid to the potential of novel cellular tests such as basophil activation tests and component-resolved diagnosis with recombinant venom allergens in the diagnostic approach of patients with difficult diagnosis, i.e. cases in whom traditional venom specific IgE and skin tests yield equivocal or negative results. Finally, this review also covers the recent discoveries in the field of proteome research of Hymenoptera venoms and the selection of cell types for recombinant allergens production.

Keywords::

• allergy
• basophil activation
• component-resolved diagnostics
• Hymenoptera venom
• IgE
• proteomics
• recombinant expression
• venomics

Acknowledgements

V Sabato is a Clinical Researcher of the Research Foundation Flanders (FWO: 1700614N). DG Ebo is a Senior Clinical Researcher of the Research Foundation Flanders (FWO: 1800614N). M Van Vaerenbergh received a doctoral fellowship of IWT, the government agency for Innovation by Science and Technology.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Hymenoptera venom allergy constitutes a potential life-threatening condition with considerable risk of diagnostic error.

• Although correct diagnosis is a prerequisite for Hymenoptera venom immunotherapy, correct entomological identification of the culprit insect is not always straightforward.

• It is increasingly recognized that novel tests such as component-resolved diagnostics and basophil activation tests can improve diagnosis, particularly in patients who display negative or equivocal results for traditional venom sIgE tests and venom skin tests. However, additional collaborative studies are required before these can enter mainstream application.

• Despite the high efficiency of venom immunotherapy, the mechanisms and biomarkers associated with clinical efficacy remain elusive. Studies monitoring basophil responsiveness have demonstrated this test to be of better predictive value than venom skin tests and sIgE that generally fail to reflect induction of clinical tolerance.