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      Anaphylaxis to Insect Venom Allergens: Role of Molecular Diagnostics

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          Abstract

          Anaphylaxis due to Hymenoptera stings is one of the most severe consequences of IgE-mediated hypersensitivity reactions. Although allergic reactions to Hymenoptera stings are often considered as a general model for the underlying principles of allergic disease, diagnostic tests are still hampered by a lack of specificity and venom immunotherapy by severe side effects and incomplete protection. In recent years, the knowledge about the molecular composition of Hymenoptera venoms has significantly increased and more and more recombinant venom allergens with advanced characteristics have become available for diagnostic measurement of specific IgE in venom-allergic patients. These recombinant venom allergens offer several promising possibilities for an improved diagnostic algorithm. Reviewed here are the current status, recent developments, and future perspectives of molecular diagnostics of venom allergy. Already to date, it is foreseeable that component-resolution already has now or will in the future have the potential to discriminate between clinically significant and irrelevant sensitization, to increase the specificity and sensitivity of diagnostics, to monitor immunotherapeutic intervention, and to contribute to the understanding of the immunological mechanisms elicited by insect venoms.

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          Most cited references94

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          Insights into social insects from the genome of the honeybee Apis mellifera.

          Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.
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            First European data from the network of severe allergic reactions (NORA).

            Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling.
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              Diagnosis of Hymenoptera venom allergy.

              The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10-50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross-reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE-mediated or non-IgE-mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom-allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health-related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom-specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.
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                Author and article information

                Contributors
                +352-269-70-829 , markus.ollert@lih.lu
                +49-89-318-726-25 , simon.blank@helmholtz-muenchen.de
                Journal
                Curr Allergy Asthma Rep
                Curr Allergy Asthma Rep
                Current Allergy and Asthma Reports
                Springer US (New York )
                1529-7322
                1534-6315
                3 July 2015
                3 July 2015
                2015
                : 15
                : 5
                : 26
                Affiliations
                [ ]Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, L-4354 Esch-sur-Alzette, Luxembourg
                [ ]Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark
                [ ]Center of Allergy and Environment (ZAUM), Institute of Allergy Research, Technical University and Helmholtz Center Munich, Ingolstädter Landstraße 1, D-85764 Munich, Germany
                Article
                527
                10.1007/s11882-015-0527-z
                4490169
                26139335
                65ff8d0c-39cf-42c5-9253-a183687615c0
                © The Author(s) 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                Categories
                Immunologic/Diagnostic Tests in Allergy (M Chapman and A Pomés, Section Editors)
                Custom metadata
                © Springer Science+Business Media New York 2015

                Immunology
                apis mellifera,component-resolved diagnosis,hymenoptera venom,insect venom allergy,recombinant allergens,vespula vulgaris

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