Zusammenfassung
Immunglobulin-E (IgE)-vermittelte allergische Erkrankungen zeichnen sich durch einen heterogenen klinischen Phänotyp und sehr unterschiedliche Sensibilisierungsprofile aus. Sie weisen somit einen ausgesprochen individuellen Charakter auf. Neben einer genetischen Prädisposition spielen in der Sensibilisierungsphase und bei der Auslösung von Symptomen die verschiedensten Umweltfaktoren eine Rolle. Da die wichtigsten klinisch relevanten Allergene inzwischen in gereinigter Form als rekombinante Allergene zur Verfügung stehen, kann das Sensibilisierungsmuster der betroffenen Allergiker mittels Komponenten-aufgelöster In-vitro-Diagnostik auf molekularer Ebene erfasst werden. Solche Daten erlauben möglicherweise Aussagen über den Schwergrad und die Persistenz der allergischen Erkrankung sowie zur Prognose einer spezifischen Immuntherapie (SIT). Das Potenzial dieses Ansatzes ist noch in kontrollierten klinischen Studien zu prüfen. Weiterhin werden im vorliegenden Beitrag im Kontext der atopischen Dermatitis (AD), der allergischen Rhinitis, des allergischen Asthmas und des atopischen Marsches verschiedene weitere Screening-Biomarker, diagnostische und prognostische Biomarker, Biomarker für den Schweregrad der Erkrankungen und prädiktive Biomarker vorgestellt und diskutiert. Ein erheblicher Anteil der Immuntherapien allergischer Erkrankungen wird traditionell in personalisierter Weise mit Individualrezepturen durchgeführt, die häufig aus Mischungen zahlreicher Allergenextrakte bestehen. Eine gesicherte Evidenz zur Wirksamkeit und Sicherheit dieses Ansatzes liegt nicht vor. In Deutschland wurde durch die Therapieallergene-Verordnung (TAV) festgelegt, dass Allergenprodukte für die SIT von Insektengiftallergien, gegen Pollen früh blühender Bäume und Gräserpollen sowie gegen Hausstaubmilben zukünftig ausschließlich als zugelassene Arzneimittel in den Verkehr gebracht werden dürfen. Die personalisierte SIT mit Individualrezepturen wird somit auf seltenere allergische Erkrankungen eingeschränkt, für die Generierung umfassender klinischer Daten aufgrund der geringen Patientenzahlen problematisch ist. Verschiedene rekombinante Allergene werden inzwischen in klinischen Prüfungen der Phase III untersucht. Im Gegensatz zu Allergenextrakten bieten rekombinante Allergene die Möglichkeit, den Patienten mit einer Mischung exakt derjenigen Moleküle zu behandeln, gegen die eine Sensibilisierung besteht. Die Umsetzung dieses personalisierten, innovativen Immuntherapieansatzes innerhalb des bestehenden regulatorischen Rahmens stellt allerdings eine Herausforderung dar.
Abstract
Immunoglobulin E (IgE) mediated allergic diseases are characterised by heterogeneous clinical phenotypes and a large variety of different sensitisation patterns. Apart from genetic predisposition several environmental factors play a role in sensitisation and elicitation of symptoms. Since the majority of clinically relevant allergens are now available as purified recombinant allergens component-resolved in vitro diagnosis allows the sensitization profile of allergic patients to be determined at the molecular level. Such data may allow physicians to draw conclusions on the severity and persistence of a given allergic disease and to predict the outcome of allergen-specific immunotherapy (SIT) However, the potential of this approach needs to be demonstrated in controlled clinical trials. Moreover, in the context of atopic dermatitis, allergic rhinitis, allergic bronchial asthma as well as the atopic march several screening-biomarkers, diagnostic and prognostic biomarkers, biomarkers of severity and predictive biomarkers are presented and discussed in this article. Traditionally a relevant proportion of allergen-specific immunotherapies is performed in a personalised manner using named patient products manufactured on the basis of an individual prescription. Such named patient products are often mixtures containing several allergen extracts from different sources. However, there is no proven evidence for the safety and efficacy of this approach. In Germany the Therapy Allergen Ordinance (“Therapieallergene-Verordnung”, TAV) regulates that in the future allergen products for SIT of insect venom allergies, allergies to pollen of early flowering trees and grass pollen and house dust mite allergies cannot be marketed as named patient products, but always require a marketing authorisation. Thus personalised SIT with named patient products is restricted to the treatment of less prevalent allergies, for which the generation of state-of-the-art clinical data is more difficult. Several recombinant allergens are currently evaluated in phase III clinical trials. In contrast to allergen extracts recombinant allergens offer the possibility to treat patients with a precisely adjusted mixture of the disease-eliciting allergen molecules. However, the implementation of this personalised approach to SIT within the given regulatory framework represents a challenge to regulators.
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Einhaltung ethischer Richtlinien
Interessenkonflikt. Die folgenden Aktivitäten der letzten 5 Jahre von S. Vieths könnten als potenzieller Interessenkonflikt in Bezug auf den vorliegenden Artikel wahrgenommen werden: Ein Vortragshonorar von Phadia (heute Thermofisher), Uppsala, ein Honorar der Fresenius Akademie, Dortmund für die Organisation eines Seminars über Nahrungsmittelallergene, Honorare als Expertengutachter für die Allergen Online Datenbank des Food Allergy Resource and Research Program, University of Nebraska, Lincoln, NE, USA, sowie eine frühere Beteiligung als Gesellschafter des Instituts für Produktqualität in Berlin und Beratungshonorare durch das Institut. T. Bieber: kein Interessenkonflikt anzugeben. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Vieths, S., Bieber, T. Personalisierte Ansätze zur Diagnostik und Therapie von Allergien. Bundesgesundheitsbl. 56, 1531–1537 (2013). https://doi.org/10.1007/s00103-013-1821-3
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DOI: https://doi.org/10.1007/s00103-013-1821-3
Schlüsselwörter
- Allergische Erkrankungen
- Biomarker
- Personalisierte Immuntherapie
- Individualrezeptur
- Rekombinante Allergene