Diagnostics in Hymenoptera venom allergy: current concepts and developments with special focus on molecular allergy diagnostics

Abstract

BackgroundThe high rate of asymptomatic sensitization to Hymenoptera venom, difficulty in correctly identifying Hymenoptera and loss of sensitization over time make an accurate diagnosis of Hymenoptera venom allergy challenging. Although routine diagnostic tests encompassing skin tests and the detection of venom-specific IgE antibodies with whole venom preparations are reliable, they offer insufficient precision in the case of double sensitized patients or in those with a history of sting anaphylaxis, in whom sensitization cannot be proven or only to the presumably wrong venom.MethodsSystematic literature research and review of current concepts of diagnostic testing in Hymenoptera venom allergy.Results and discussionImprovements in diagnostic accuracy over recent years have mainly been due to the increasing use of molecular allergy diagnostics. Detection of specific IgE antibodies to marker and cross-reactive venom allergens improves the discrimination between genuine sensitization and cross-reactivity, and this provides a better rationale for prescribing venom immunotherapy. The basophil activation test has also increased diagnostic accuracy by reducing the number of Hymenoptera venom sensitizations overlooked with routine tests. This paper reviews current concepts of diagnostic testing in Hymenoptera venom allergy and suggests fields for further development.

Current challenges in molecular diagnostics of insect venom allergy

“…Double positive results (e.g., to HBV and YJV) are common findings in venom extract-based allergy diagnostics. Previous studies conducted in Central Europe demonstrated that up to 47% of patients with anaphylactic sting reactions (n = 530) display double positivity to HBV and YJV [17]. Unfortunately, often this result does not reflect true sensitizations to different insects but is rather associated with the detection of clinically irrelevant cross-reactive IgE [10].…”

“…Percentages of sequence identity (red triangles) and levels of 3-D structure similarities (green triangles) expressed by the root-mean square deviation (RMSD) of the atomic positions on the 3-D models are provided. RMSD values between 0-2 Å indicate a high-quality model with lower values indicating higher similarity to the template allergic patients (42-52%) [17], little or no IgE reactivity to CCD-free rVes v 2 has been reported in YJV allergic patients [33]. One explanation for the lack of peptide based cross-reactivity between YJ and HB hyaluronidases could be differences in their threedimensional structures and surface epitopes, which only display a low degree of similarity when analyzed by computational modeling [34,35].…”

Sensitization to Hymenoptera venom marker allergens: Prevalence, predisposing factors, and clinical implications

“…In accordance with previous studies on the natural course of sensitization to Hymenoptera venoms, our data suggest that sensitization to VV marker allergens peaks shortly after the sting, subsequently wanes, and may fall below the limits of detection within a couple of years. 5,7,21,26,27…”

“…5 A recent prospective study assessing the outcome of deliberate sting challenges, however, did not confirm an increased risk in asymptomatically sensitized subjects when compared to the general population. 7 IgE testing targeting single venom marker allergens was recently introduced for routine diagnostic assessment of Hymenoptera venom-allergic patients: 2,3 Up to 90% of patients allergic to Vespula venom (VV) are considered to be sensitized to rVes v 5 8,9 and just under 60% to rVes v 1. 7 IgE testing targeting single venom marker allergens was recently introduced for routine diagnostic assessment of Hymenoptera venom-allergic patients: 2,3 Up to 90% of patients allergic to Vespula venom (VV) are considered to be sensitized to rVes v 5 8,9 and just under 60% to rVes v 1.…”

“…6 The term "marker allergen" refers to components indicative of genuine sensitization to a given venom. 7 IgE testing targeting single venom marker allergens was recently introduced for routine diagnostic assessment of Hymenoptera venom-allergic patients: 2,3 Up to 90% of patients allergic to Vespula venom (VV) are considered to be sensitized to rVes v 5 8,9 and just under 60% to rVes v 1. 9 The use of a diagnostic cut-off of 0.10 kU A /L instead of the traditional threshold of 0.35 kU A /L has been proposed to further increase diagnostic sensitivity in patients with low total IgE levels and/or mastocytosis.…”