Component‐resolved diagnostics to direct in venom immunotherapy: Important steps towards precision medicine

Abstract

Stings of Hymenoptera can induce IgE-mediated systemic and even fatal allergic reactions. Venom-specific immunotherapy (VIT) is the only disease-modifying and curative treatment of venom allergy. However, choosing the correct venom for VIT represents a necessary prerequisite for efficient protection against further anaphylactic sting reactions after VIT. In the past, therapeutic decisions based on the measurement of specific IgE (sIgE) levels to whole venom extracts were not always straightforward, especially when the patient was not able to identify the culprit insect. In the last years, the increasing knowledge about the molecular structure and relevance of important venom allergens and their availability as recombinant allergens, devoid of cross-reactive carbohydrate determinants, resulted in the development of an advanced component-resolved diagnostics (CRD) approach in venom allergy. Already to date, CRD has increased the sensitivity of sIgE detection and enabled the discrimination between primary sensitization and cross-reactivity, particularly in patients with sensitization to both honeybee and vespid venom. Hence, CRD in many patients improves the selection of the appropriate immunotherapeutic intervention. Moreover, the detailed knowledge about sensitization profiles on a molecular level might open new options to identify patients who are at increased risk of side-effects or not to respond to immunotherapy. Therefore, increasing potential of CRD becomes evident, to direct therapeutic decisions in a personalized and patient-tailored manner. Reviewed here are the state of the art options, recent developments and future perspectives of CRD of Hymenoptera venom allergy.

CAP-Inhibition, Molecular Diagnostics, and Total IgE in the Evaluation of <b><i>Polistes</i></b> and <b><i>Vespula</i></b> Double Sensitization

“…However, current routinely performed in vitro and in vivo diagnostics are not able to clinically distinguish between irrelevant cross-reactivity and real double sensitization to vespid venom. This circumstance leads to the prescription of inappropriate, expensive, and long-term double-venom immunotherapy (VIT) [2]. Component-resolved diagnostics (CRD) and basophil activation testing (BAT) have made a remarkable contribution in distinguishing between bee and yellow jacket venom allergy [2, 4, 5].…”

“…This circumstance leads to the prescription of inappropriate, expensive, and long-term double-venom immunotherapy (VIT) [2]. Component-resolved diagnostics (CRD) and basophil activation testing (BAT) have made a remarkable contribution in distinguishing between bee and yellow jacket venom allergy [2, 4, 5]. Regarding cross-reactivity between vespid species, suitable antigens in CRD required to identify genuine sensitizations are still missing, and the role of BAT has not yet been well investigated.…”

“…Seven Italian centers consecutively enrolled 112 vespid venom-allergic patients with a history of Mueller grade II–IV systemic reactions and double sensitization to VV and PD venoms according to skin tests and/or wvIgE (i3, i77) (ImmunoCAP, Thermo Fisher Scientific) [10], and CRD (Ves v 5, Pol d 5) (ImmunoCAP) [2]. …”

“…In general terms, CRD adds important accuracy to allergy diagnostics [2] but fails to demonstrate a meaningful superiority in distinguishing between VV and PP, when compared to skin tests (Fig. 1).…”

From basic science to diagnostics ‐ History of a patent on a honeybee venom allergen

“…In the past, therapeutic decisions based on specific IgE (sIgE) levels to whole venom extracts were not always straightforward. The presence of cross‐reactive allergens and cross‐reactive carbohydrate determinants (CCDs) in the extracts complicated the discrimination between cross‐reactivity and true allergy to more than one venom . In the last years, the increasing knowledge of the composition of relevant venom allergens and the availability of recombinant CCD‐free marker allergens resulted in the development of an advanced component‐resolved diagnostics (CRD) of venom allergy .…”