Dokument

Zusammenfassung:
Allergische Erkrankungen haben in den letzten Jahren in Industrie- sowie Entwicklungsländern kontinuierlich zugenommen. Die aktuellen Behandlungsmöglichkeiten beschränken sich hauptsächlich auf symptomatische Therapieverfahren. Die einzige kurative Therapieform ist derzeit die spezifische Immuntherapie (SIT). Verschiedene Applikationsschemata und Aufbereitungsformen von Allergenen sind im Handel erhältlich. Allergoide stellen dabei eine modifizierte Form von Allergenen dar und sollen sich durch reduzierte Allergenität bei erhaltener Immunogenität auszeichnen. Dadurch sei eine sicherere und schnellere Dosissteigerung im Vergleich zu unbehandelten Allergenen möglich. Obwohl in den vergangenen Jahrzehnten die Grundlagenforschung zu Mechanismen der Allergieentstehung viele Fortschritte gemacht hat, ist der genaue Mechanismus einer durch SIT induzierten Immuntoleranz nicht endgültig geklärt. Besonders die Unterschiede der Immunmodulation durch Allergoide im Vergleich zu unbehandelten Allergenen ist noch zu klären. Möglicherweise sind die beobachteten klinischen Effekte der Allergoidtherapie durch andere Mechanismen als die der SIT mit nativen Allergenen zu erklären. Ziel dieser Studie ist die Untersuchung immunologischer Grundlagen bei einer SIT mit Allergoiden (Depigoid®) von Birkenpollenallergikern über den Zeitraum des ersten Therapiejahres. Sieben Patienten mit klinisch wie auch immunologisch nachgewiesener Birkenpollenallergie konnten in die Studie eingeschlossen werden. Es wurden allergenspezifisches IgE, Gesamt-IgE und allergenspezifisches IgG4 mittels ImmunoCap gemessen. Parallel dazu erfolgte die Erfassung von Veränderungen der Frequenzen Bet v 1 (Hautallergen der Birke)-spezifischer Th1-, Th2- und Tr1-Zellen nach Allergenstimulation mittels ELISPOT. Als weitere Population regulatorischer T-Zellen (Treg) wurden CD4+CD25+CD127low Treg mittels durchflusszytometrischer Messungen charakterisiert. Der Bestimmung einer veränderten Reaktionsbereitschaft nach Allergenkontakt diente die Erfassung der Proliferation von PBMC nach Betv1- Stimulation. Parallel zu den immunologischen Parametern wurde die klinische Effektivität mittels unterschiedlicher Fragebögen ermittelt und durch zwei im Jahresabstand durchgeführte Pricktests ergänzt. Die Studienergebnisse zeigen eine marginale Verbesserung klinischer Beschwerden, wobei nur verschwindend geringe immunologische Veränderungen detektiert werden können. Die Messungen der Immunglobuline ergeben einen lediglich tendenziellen Abfall spezifischer IgE-Antikörper bei nahezu gleichbleibenden Werten für Gesamt-IgE und allergenspezifisches IgG4. Die Frequenzen für Betv1-spezifische Th2-Zellen weisen einen Anstieg im ersten Therapiemonat sowie am Ende des ersten Therapiejahres auf. Demgegenüber zeigt sich ein leichter Abfall von Th1-Zellen und somit ein Anstieg des Th2/Th1-Verhältnisses. Bei den Treg kann ein leichter Anstieg von Tr1-Zellen bei gleichbleibendem Anteil von CD4+CD25+CD127low-Treg beobachtet werden. Insgesamt sprechen die erhobenen Daten gegen eine Toleranzinduktion durch die Allergoidtherapie, so dass neben einer für Allergoide typischen Allergenitätsreduktion auch von einer Verringerung der Immunogenität ausgegangen werden muss. Alternativ könnten andere immunologische Mechanismen als die bei einer konventionellen SIT mit nativen Allergenen für die Toleranzinduktion unter einer SIT mit Allergoiden verantwortlich sein. Zu beachten ist bei diesen Hypothese, dass eine abschließende Klärung auf Grund der geringen Patientenzahl in dieser Studie nicht möglich ist. In Zukunft durchgeführte Studien mit höheren Patientenzahlen sollten daher die Frage nach den immunologischen Mechanismen einer SIT mit Allergoiden eingehender untersuchen.

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