Marker allergens in Hymenoptera venom allergy — Characteristics and potential use in precision medicine

Abstract Background A comprehensive diagnostic work-up is essential to ensure adequate patient management for the potentially life-threatening condition of Hymenoptera venom allergy (HVA). This includes an unambiguous identification of the allergy-relevant venom as prerequisite for successful venom-specific immunotherapy (VIT). If the clinical history does not allow the identification of the culprit insect, diagnosis is often hampered by positive test results to various venoms. Modern component-resolved diagnostics (CRD) applying marker allergens of Hymenoptera venoms has created new opportunities which facilitate therapeutic decisions and may allow personalized risk stratification for individual patients. Methods Comprehensive literature search and critical analysis of recently published studies on Hymenoptera venom allergens and CRD. Results and discussion Changing the research focus from whole venom extracts to individual allergenic molecules led to the development of CRD in HVA. The currently available CRD is a valuable tool to resolve cross-reactivity and primary sensitization, particularly in honeybee and vespid venom allergy. Hence, CRD has simplified therapeutic decisions in case of multiple positive test results, especially in patients who were not able to identify the culprit insect or in cases of discrepancies between clinical history and classical diagnostic results. Moreover, there is first evidence that sensitization to particular allergens might serve as biomarkers to predict risk for severe side-effects during VIT or even for VIT failure. To date, a clear limitation of CRD is the currently available allergen panel which does not allow a definite resolution of allergy to different vespid species such as yellow jackets and European paper wasps.

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Robustness of Serologic Investigations for Chikungunya and Mayaro Viruses following Coemergence

mSphere ◽

10.1128/msphere.00915-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 2

Author(s):

Carlo Fischer ◽

Fernando Bozza ◽

Xiomara Jeanleny Merino Merino ◽

Celia Pedroso ◽

Edmilson F. de Oliveira Filho ◽

...

Keyword(s):

Latin America ◽

False Positive ◽

Chikungunya Virus ◽

Cross Reactivity ◽

Positive Test ◽

Antibody Detection ◽

Test Results ◽

Specific Patient ◽

False Positive Test ◽

Mayaro Virus

ABSTRACT Since 2013, the arthropod-borne Chikungunya virus (CHIKV) has cocirculated with the autochthonous Mayaro virus (MAYV) in Latin America. Both belong to the same alphavirus serocomplex, termed the Semliki Forest serocomplex. The extent of antibody cross-reactivity due to the antigenic relatedness of CHIKV and MAYV in commonly used serologic tests remains unclear. By testing 64 CHIKV- and 37 MAYV-specific sera from cohort studies conducted in Peru and Brazil, we demonstrate about 50% false-positive test results using commercially available enzyme-linked immunosorbent assays (ELISAs) based on structural antigens. In contrast, combining ELISAs for CHIKV and MAYV significantly increased positive predictive values (PPV) among all cohorts from 35.3% to 88.2% for IgM and from 61.3% to 96.8% for IgG (P < 0.0001). Testing of longitudinally collected CHIKV-specific patient sera indicated that ELISA specificity is highest for IgM testing at 5 to 9 days post-onset of symptoms (dpo) and for IgG testing at 10 to 14 dpo. IgG cross-reactivity in ELISA was asymmetric, occurring in 57.9% of MAYV-specific sera compared to 29.5% of CHIKV-specific sera. Parallel plaque reduction neutralization testing (PRNT) for CHIKV and MAYV increased the PPV from 80.0% to 100% (P = 0.0053). However, labor-intense procedures and delayed seroconversion limit PRNT for patient diagnostics. In sum, individual testing for CHIKV or MAYV only is prone to misclassifications that dramatically impact patient diagnostics and sero-epidemiologic investigation. Parallel ELISAs for both CHIKV and MAYV provide an easy and efficient solution to differentiate CHIKV from MAYV infections. This approach may provide a template globally for settings in which alphavirus coemergence imposes similar problems. IMPORTANCE Geographically overlapping transmission of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in Latin America challenges serologic diagnostics and epidemiologic surveillance, as antibodies against the antigenically related viruses can be cross-reactive, potentially causing false-positive test results. We examined whether widely used ELISAs and plaque reduction neutralization testing allow specific antibody detection in the scenario of CHIKV and MAYV coemergence. For this purpose, we used 37 patient-derived MAYV-specific sera from Peru and 64 patient-derived CHIKV-specific sera from Brazil, including longitudinally collected samples. Extensive testing of those samples revealed strong antibody cross-reactivity in ELISAs, particularly for IgM, which is commonly used for patient diagnostics. Cross-neutralization was also observed, albeit at lower frequencies. Parallel testing for both viruses and comparison of ELISA reactivities and neutralizing antibody titers significantly increased diagnostic specificity. Our data provide a convenient and practicable solution to ensure robust differentiation of CHIKV- and MAYV-specific antibodies.

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Dissecting cross-reactivity in hymenoptera venom allergy by circumvention of α-1,3-core fucosylation

Molecular Immunology ◽

10.1016/j.molimm.2009.10.005 ◽

2010 ◽

Vol 47 (4) ◽

pp. 799-808 ◽

Cited By ~ 79

Author(s):

Henning Seismann ◽

Simon Blank ◽

Ingke Braren ◽

Kerstin Greunke ◽

Liliana Cifuentes ◽

...

Keyword(s):

Cross Reactivity ◽

Hymenoptera Venom ◽

Venom Allergy ◽

Hymenoptera Venom Allergy ◽

Core Fucosylation

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Characterization of New Allergens from the Venom of the European Paper Wasp Polistes dominula

Toxins ◽

10.3390/toxins13080559 ◽

2021 ◽

Vol 13 (8) ◽

pp. 559

Author(s):

Johannes Grosch ◽

Bernadette Eberlein ◽

Sebastian Waldherr ◽

Mariona Pascal ◽

Clara San Bartolomé ◽

...

Keyword(s):

Molecular Mechanisms ◽

Cross Reactivity ◽

Paper Wasp ◽

Hymenoptera Venom ◽

Venom Allergy ◽

Allergen Specific Immunotherapy ◽

Polistes Dominula ◽

Factor C ◽

Venom Proteins

Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species’ sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom—immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)—were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20–40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.

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Stinging Insect Allergens

Current Protein and Peptide Science ◽

10.2174/1389203720666191120130209 ◽

2020 ◽

Vol 21 (2) ◽

pp. 142-152 ◽

Cited By ~ 1

Author(s):

Le Cui ◽

Ying-Yang Xu ◽

Xiu-Jie Wang ◽

Kai Guan

Keyword(s):

Specific Ige ◽

Cross Reactivity ◽

Hymenoptera Venom ◽

Venom Allergy ◽

Hymenoptera Venom Allergy ◽

Predictive Values ◽

Common Causes ◽

History Of ◽

The Common ◽

Stinging Insect

Hymenoptera venom allergy is one of the common causes of anaphylaxis. However, when physicians make the diagnosis of Hymenoptera venom allergy, the history of being stung is not always consistent with the results of venom-specific IgE. With the development of component-resolved diagnosis, it is possible to accurately localize an allergic reaction to certain sensitized proteins. This paper reviewed the studies that have addressed the identified allergenicity and cross-reactivity of Hymenoptera venom allergens accepted by the WHO/IUIS Nomenclature Sub-committee, the componentresolved diagnosis of Hymenoptera venom allergy and its predictive values for the efficacy and safety of venom immunotherapy. Also special attention was paid to the spread of Hymenoptera venom allergy in Asian countries.

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The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.210024 ◽

2021 ◽

Vol 42 (4) ◽

pp. 350-356 ◽

Cited By ~ 1

Author(s):

Ayse Engin ◽

Fatma B. Oktelik ◽

Aslı Gelincik ◽

Aytul Sin ◽

Betul A. Sin ◽

...

Keyword(s):

Clinical Symptoms ◽

Specific Ige ◽

Cross Reactivity ◽

Bee Venom ◽

Skin Tests ◽

Hymenoptera Venom ◽

Venom Allergy ◽

Hymenoptera Venom Allergy ◽

Conventional Tests ◽

Bee Venom Allergy

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.

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