Application of recombinant antigen 5 allergens from seven allergy-relevant Hymenoptera species in diagnostics

Schiener, Maximilian; Eberlein, Bernadette; Moreno‐Aguilar, Carmen; Pietsch, Gunilla; Serrano, Pilar; McIntyre, Mareike; Schwarze, Lea; Rußkamp, Dennis; Biedermann, Tilo; Spillner, Edzard; Darsow, Ulf; Ollert, Markus; Schmidt‐Weber, Carsten B.; Blank, Simon

doi:10.1111/all.13000

Cited by 45 publications

(71 citation statements)

References 42 publications

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“…One interesting candidate, Pol d 4, which was identified in P. dominula venom but not in Vespula venom, failed as marker allergen due to low sensitization prevalence in Polistes sensitized individuals (unpublished data). All other Polistes allergens that have been described so far, have a homologous counterpart in Vespinae venom and display a high degree of peptide-based cross-reactivities [27], making them unsuitable for precise discrimination of YJV or Polistes sensitizations.…”

Section: Figmentioning

confidence: 99%

“…Due to these structural similarities, venom PLA1 and antigen 5 have limited diagnostic value for discrimination of Vespula and Polistes sensitizations [13,17]. A recent study showed significant levels of peptide-based cross-reactivity between antigen 5 from several members of Vespinae and Polistinae [27]. Venom PLA1 were shown to cross-react to a lesser extent [10,36].…”

Section: Component-resolved Diagnostics and Peptide Based Cross-reactmentioning

confidence: 99%

“…This however still needs to be investigated. To date the identification of novel subfamily biomarkers seems not very likely as the most important Vespinae and Polistinae allergens are crossreactive [27].…”

Section: Component-resolved Diagnostics and Peptide Based Cross-reactmentioning

confidence: 99%

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Current challenges in molecular diagnostics of insect venom allergy

2020

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Background Advanced component-resolved diagnostics (CRD) in Hymenoptera venom allergy (HVA) has improved the precise description of individual sensitization profiles. However, diagnostic gaps, peptidebased cross-reactivity, early identification of severe reactors and diagnosis of patients with a clear history of sting reactions but negative specific IgE and skin tests, remain challenging. Methods Systematic literature search in PubMed and critical analysis of recently published studies on insect venom allergy diagnostics. Results and discussion CRD has increased the sensitivity of IgE testing and improved the discrimination of primary sensitization from irrelevant cross-reactivity, ultimately providing a better rationale for therapeutic decisions. Despite these major advances, there is still room for improvement in routine HVA diagnostics. Peptide based cross-reactivity among homologous allergens from Vespinae and Polistinae venoms as well as still existing diagnostic gaps are particularly challenging. No marker allergens are currently available to differentiate Vespula and Polistes sensitizations. Several strategies including clinical setting of basophil activation test (BAT) for routine diagnostics, venomic analysis for the identification of novel allergens and characterization of the molecular basis of A. Perez-Riverol · T. Jakob ( )

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Section: Figmentioning

confidence: 99%

Section: Component-resolved Diagnostics and Peptide Based Cross-reactmentioning

confidence: 99%

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Current challenges in molecular diagnostics of insect venom allergy

2020

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“…stings of the different vespid species is still challenging [37,64,65]. Unique marker allergens that would allow reliable discrimination are not available and, to our opinion, will be hard to find due to the close phylogenetic distance of the species.…”

Section: Accepted Articlementioning

confidence: 99%

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

Blank

Bilò

Ollert

2018

Clin Experimental Allergy

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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.

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“…Estima-se que cerca de 50% dos doentes com alergia ao veneno destes insetos apresentem resultados positivos, TC e/ou IgE esp, tanto para veneno de abelha (Apis mellifera) como para veneno de vespa (Vespula germanica e Polistes dominula, as duas principais espécies no nosso país) 1,2 . Por outro lado, alguns autores descrevem que mais de 30% dos doentes com RS à picada de insetos apresentam TC e IgE esp negativos, provavelmente devido à sensibilidade limitada destes métodos 3 . A dupla positividade para veneno de abelha e veneno de vespa pode representar uma verdadeira dupla sensibilização ou reatividade cruzada a ambos os venenos devido à homologia de sequência entre proteínas destes venenos, tais como hialuronidases ou mesmo determinantes dos carboidratos (CCD).…”

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Biomarcadores de sensibilização primária e reatividade cruzada em doentes alérgicos a veneno de himenópteros

Pestana

Melo

Pedro

et al. 2019

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Biomarcadores de sensibilização primária e reatividade cruzada em doentes alérgicos a veneno de himenópteros Biomarkers of primary sensitization and cross-reactivity in patients allergic to Hymenoptera venom RESUMO Introdução: A maioria dos doentes com alergia à picada de himenópteros apresenta dupla positividade (testes cutâneos-TC/IgE específica-sIgE) para veneno de abelha (A), vespa (V) e Polistes (P), constituindo um problema quer no diagnóstico quer na seleção para imunoterapia específica (IT). Objetivo: Caraterização do perfil de sensibilização de doentes alérgicos à picada de himenópteros, através da utilização de alergénios recombinantes, fosfolipases, hialuronidases e determinantes dos carboidratos para distinguir dupla sensibilização de reatividade cruzada. Avaliação da contribuição do teste de ativação de basófilos (TAB) no diagnóstico. Métodos: Foram incluídos 124 doentes com história de reação sistémica (RS), não submetidos a IT, e um grupo-controlo de 30 indivíduos sem história de reação.Os TC foram realizados com extratos comerciais (EC) de veneno, assim como determinação de sIgE sérica. Doseou-se também sIgE para recombinantes, Api m1, Ves v5, Ves v1, Pol d5 e CCD. Em doentes com TC/sIgE negativos, foi realizado o TAB em seis concentrações. Resultados: Baseada na sIgE, 66 doentes (53%) encontravam-se polissensibilizados e 38 doentes (31%) monossensibilizados. Em 20 doentes (16%) os TC/sIgE foram negativos. Dos 66 doentes polissensibilizados, 32 (49%) apresentavam dupla sensibilização, 23 (35%) reatividade cruzada e 11 (16%) sIgE negativa para recombinantes. A sIgE para CCD foi positiva em 25 doentes, todos com dupla sensibilização com EC, demonstrando reatividade cruzada em 23. Os 20 doentes com TC/sIgE negativos apresentaram sIgE negativa para os recombinantes. A especificidade para os quatro componentes moleculares foi elevada. O TAB foi realizado em 5 doentes, sendo posi-R e v P o r t I m u n o a l e r g o l o g i a 2 0 1 9 ; 2 7 ( 2 ) : 1 0 5 -1 1 4 Data de receção / A s picadas de insetos desencadeiam, na maioria dos casos, reações locais devido à toxicidade do veneno. No entanto, está descrito que cerca de 3,5% da população em geral tem história de reação sistémica (RS), incluindo anfilaxia 1 . A imunoterapia (IT) é considerada um tratamento altamente eficaz na prevenção de reações graves em doentes alérgicos ao veneno de himenópteros, mas requer um diagnóstico cuidadoso que visa identificar não só a alergia mas também o inseto responsável 1,2 . Porém, o diagnóstico, que se baseia na história clínica, testes cutâneos (TC) e na quantificação de anticorpos IgE específicas séricas tivo em 3 para veneno (A). Conclusão: Os alergénios recombinantes para veneno (A) e (V) complementam o diagnóstico de alergia à picada de himenópteros, permitindo distinguir dupla sensibilização de reatividade cruzada e uma melhor seleção de doentes para IT. O TAB poderá ser um contributo importante em casos de difícil diagnóstico. Palavras-chave: Alergia a veneno de himenópteros, alergénios recombinantes, dupla sensi...

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Application of recombinant antigen 5 allergens from seven allergy-relevant Hymenoptera species in diagnostics

Cited by 45 publications

References 42 publications

Current challenges in molecular diagnostics of insect venom allergy

Current challenges in molecular diagnostics of insect venom allergy

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

Biomarcadores de sensibilização primária e reatividade cruzada em doentes alérgicos a veneno de himenópteros

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