Anaphylaxis to insect venom allergens: role of molecular diagnostics

Abstract

Anaphylaxis due to Hymenoptera stings is one of the most severe consequences of IgE-mediated hypersensitivity reactions. Although allergic reactions to Hymenoptera stings are often considered as a general model for the underlying principles of allergic disease, diagnostic tests are still hampered by a lack of specificity and venom immunotherapy by severe side effects and incomplete protection. In recent years, the knowledge about the molecular composition of Hymenoptera venoms has significantly increased and more and more recombinant venom allergens with advanced characteristics have become available for diagnostic measurement of specific IgE in venom-allergic patients. These recombinant venom allergens offer several promising possibilities for an improved diagnostic algorithm. Reviewed here are the current status, recent developments, and future perspectives of molecular diagnostics of venom allergy. Already to date, it is foreseeable that component-resolution already has now or will in the future have the potential to discriminate between clinically significant and irrelevant sensitization, to increase the specificity and sensitivity of diagnostics, to monitor immunotherapeutic intervention, and to contribute to the understanding of the immunological mechanisms elicited by insect venoms.

Fig. 1

Molecular sIgE diagnostics: avoidance of glycan-specific binding and increased assay sensitivity. a Schematic representations of the core glycosylation of humans and insects. The latter carries an additional alpha-1,3-fucose residue which is not present in human carbohydrate structures and therefore is highly immunogenic. It can induce the generation of cross-reactive human IgE antibodies. (GlcNAc, N-acetylglucosamine; man, mannose; fuc, fucose). b Molecular diagnostics with recombinant marker allergens are able to exclude “false-positive” test results due to IgE directed against cross-reactive carbohydrate determinants (CCDs) or homologous allergens present in venom extracts. Thus, the detection of true sensitizations is markedly improved. c Molecular diagnostics with recombinant allergens is able to uncover IgE sensitizations to allergens that are underrepresented, labile, degraded, or masked in venom extracts and thereby helps to avoid “false-negative” test results