Component resolution reveals additional major allergens in patients with honeybee venom allergy

Köhler, Julian; Blank, Simon; Müller, Sabine; Bantleon, Frank; Frick, Marcel; Huss‐Marp, Johannes; Lidholm, Jonas; Spillner, Edzard; Jakob, Thilo

doi:10.1016/j.jaci.2013.10.060

Cited by 156 publications

(228 citation statements)

References 34 publications

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“…[104][105][106] It also appears that the broad sensitization pattern in honeybee venom-allergic patients may play a role in the lower effectiveness of honeybee VIT. 107 For example, some patients are predominantly sensitized to Api m 10, which may be underrepresented in certain available honeybee venom preparations. …”

Section: Adherencementioning

confidence: 99%

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy

Sturm

Varga

Roberts

et al. 2017

Allergy

383

528

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Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

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Section: Adherencementioning

confidence: 99%

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy

Sturm

Varga

Roberts

et al. 2017

Allergy

383

528

View full text Add to dashboard Cite

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“…Four and 8 patients were administered a maintenance dose of 100 μg Api m 1 is the dominant sensitizer in patients with HBV allergy, regardless of whether the native [6] or recombinant [4,5] antigen is used. In the present study, nApi m 1 was recognized by 100% of patients, who were divided into 2 phenotype groups on the basis of a cutoff of 0.35 kU/L.…”

Section: Clinical Changes Bvit Safetymentioning

confidence: 99%

“…The combined use of these 3 components, which make up the bulk of the dry weight of venom, was found to increase diagnostic performance by 15% compared with the use of rApi m 1 alone [9]. A later study using 6 different HBV components showed the complexity of sensitization profiles in patients with HBV allergy [4].…”

Section: Introductionmentioning

confidence: 96%

“…The best known are phospholipase A2 (Api m 1), hyaluronidase (Api m 2), and melittin (Api m 4). Api m 1 is the most common allergen detected by specific IgE (sIgE) determination, regardless of the method used [4][5][6]. Api m 2 is a cross-reactivity marker [7], while Api m 4 is a 2.84-kDa peptide that is found in abundance in venom [8] but has been associated with low allergenicity [4].…”

Section: Introductionmentioning

confidence: 99%

“…Api m 1 is the most common allergen detected by specific IgE (sIgE) determination, regardless of the method used [4][5][6]. Api m 2 is a cross-reactivity marker [7], while Api m 4 is a 2.84-kDa peptide that is found in abundance in venom [8] but has been associated with low allergenicity [4]. The combined use of these 3 components, which make up the bulk of the dry weight of venom, was found to increase diagnostic performance by 15% compared with the use of rApi m 1 alone [9].…”

Section: Introductionmentioning

confidence: 99%

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IgE-Api m 4 Is Useful for Identifying a Particular Phenotype of Bee Venom Allergy

Ruiz¹,

Serrano²,

Moreno‐Aguilar³

2016

J Investig Allergol Clin Immunol

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Background and Objective: Different clinical behaviors have been identified in patients allergic to bee venom. Compound-resolved diagnosis could be an appropriate tool for investigating these differences. The aims of this study were to analyze whether specific IgE to Api m 4 (sIgE-Api m 4) can identify a particular kind of bee venom allergy and to describe response to bee venom immunotherapy (bVIT). Methods: Prospective study of 31 patients allergic to bee venom who were assigned to phenotype group A (sIgE-Api m 4 <0.98 kU/L), treated with native aqueous (NA) extract, or phenotype group B (sIgE-Api m 4 ≥0.98 kU/L), treated with purified aqueous (PA) extract. Sex, age, cardiovascular risk, severity of preceding sting reaction, exposure to beekeeping, and immunological data (intradermal test, sIgE/ sIgG4-Apis-nApi m 1, and sIgE-rApi m 2-Api m 4 were analyzed. Systemic reactions (SRs) during bVIT build-up were analyzed. Immunological and sting challenge outcomes were evaluated in each group after 1 and 2 years of bVIT. Results: Phenotype B patients had more severe reactions (P=.049) and higher skin sensitivity (P=.011), baseline sIgE-Apis (P=.0004), sIgE-nApi m 1 (P=.0004), and sIgG4-Apis (P=.027) than phenotype A patients. Furthermore, 41% of patients in group B experienced SRs during the build-up phase with NA; the sting challenge success rate in this group was 82%. There were no significant reductions in serial intradermal test results, but an intense reduction in sIgE-nApi m 1 (P=.013) and sIgE-Api m 4 (P=.004) was observed after the first year of bVIT. Conclusion: Use of IgE-Api m 4 as the only discrimination criterion demonstrated differences in bee venom allergy. Further investigation with larger populations is necessary.

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Molecular diagnostics and inhibition of cross‐reactive carbohydrate determinants in Hymenoptera venom allergy

Jovanovic

Perić-Popadić

Djuric

et al. 2023

Clinical & Translational All

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Background The composition of venom extracts, cross‐reactive carbohydrate determinants (CCD) and the component‐resolved diagnostics (CRD) are important fields of investigation. IgE‐reactivity to CCD complicates the interpretation of IgE to Hymenoptera venoms, especially in patients with multiple‐positivity. We analyzed the clinical importance of CRD and CCD‐inhibition for selection of allergens for venom immunotherapy (VIT). Methods In 71 patients, we measured specific IgE (sIgE) to honeybee venom (HBV), wasp venom (WV), hornet venom (HV), CCD, and recombinant allergens: phospholipase A2 (rApi m 1), hyaluronidase (rApi m 2), icarapin (rApi m 10), antigen 5 (rVes v 5), and phospholipase A1 (Immunoblot). In 29/71 HBV/WV/HV/CCD‐positive patients CCD‐inhibition was performed. According to CRD and CCD‐inhibition, we identified true sensitization and defined groups of multiple‐positive patients who needed CCD‐inhibition before starting VIT. Results sIgE‐rApi m 1, sIgE‐rApi m 2, and sIgE‐rApi m 10 were detected in 65.7%, 68.4%, and 58%, respectively. In HBV allergic patients, CRD sensitivity was 86.8%. In WV allergic patients, sensitivity of sIgE‐rVes v 5 was 94%. True multiple‐sensitization was found in 44.8% of HBV/WV/HV/CCD‐positive patients after CCD‐inhibition. Patients with multiple venom‐ and CCD‐positivity had more frequent severe allergic reactions (p < 0.001). CCD‐inhibition was helpful in HBV/WV/HV/CCD‐positive patients who were negative to all tested recombinant honeybee allergens. Persistence of HBV‐positivity after CCD‐inhibition requires CRD to other honeybee recombinant allergens. Conclusion CRD, using a profile of five most important recombinant allergens and CCD, has a high sensitivity for the diagnosis of venom allergy, especially in patients positive to several venom extracts. CRD and CCD‐inhibition are helpful to reveal the clinically relevant, true sensitization and improve the selection of venoms for long‐lasting VIT.

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Component resolution reveals additional major allergens in patients with honeybee venom allergy

Abstract: Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations.

Cited by 156 publications

References 34 publications

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy

IgE-Api m 4 Is Useful for Identifying a Particular Phenotype of Bee Venom Allergy

Molecular diagnostics and inhibition of cross‐reactive carbohydrate determinants in Hymenoptera venom allergy

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