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Titel:Messung der murinen anti-humanen Antikörperreaktion sowie Beurteilung der allgemeinen Aktivität und Kognition von gesunden adulten Mäusen nach Behandlung mit intravenösen Immunglobulinen
Autor:Fülber, Isabelle
Weitere Beteiligte: Dodel, Richard (Dr. med)
Veröffentlicht:2016
URI:https://archiv.ub.uni-marburg.de/diss/z2016/0371
DOI: https://doi.org/10.17192/z2016.0371
URN: urn:nbn:de:hebis:04-z2016-03714
DDC: Medizin
Titel (trans.):Evaluating the murine anti-human antibody response and assessment of general activity and cognition after treatment with human intravenous immunoglobulins in healthy adult C57/B6J mice
Publikationsdatum:2016-06-08
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Verhalten, intravenöse Immunglobuline, Medizin, immunotherapy, IVIG, behaviour, Immuntherapie, MAHA, Immunologie, Verhalten, MAHA, Kognition, IVIG, intravenous immunoglobulin

Zusammenfassung:
Präparate aus intravenösen Immunglobulinen (IVIG) sind Blutprodukte, welche bereits in der klinischen Therapie verschiedener entzündlicher, Autoimmun- oder Immundefizienzerkrankungen sowie insbesondere im Bereich der Therapieforschung von neurodegenerativen Erkrankungen wie unter anderem der Alzheimer Demenz (AD) eingesetzt werden. Der molekulare Wirkmechanismus von IVIG ist noch nicht endgültig geklärt. Hierfür fehlen unter anderem noch präklinische Einschätzungen der therapeutischen Effizienz von IVIG in Tiermodellen, welche wertvolle Informationen für den Wirkmechanismus in vivo liefern können. Um Erkenntnisse über die Wirk- und Funktionsweise von IVIG in vivo zu erhalten, ist es essentiell, die murine Reaktion auf humane Antikörper (murine anti-humane Antikörperreaktion, MAHA-Reaktion) im Tiermodell zu erfassen, bevor man immunmodulatorische Therapieversuche starten und folgend auf die therapeutische Effizienz in vivo rückschließen kann. Basierend auf der Kenntnis, dass humane Antikörper für das murine Immunsystem körperfremde Antigene darstellen, muss man davon ausgehen, dass Mäuse, denen IVIG injiziert wird eine immunologische Abwehrreaktion gegen diese körperfremden Antigene generieren. Dies führt potentiell dazu, dass Antigen-Antikörper-Komplexe ausfallen und somit nicht an der zu untersuchenden Reaktion teilhaben. Außerdem wäre es denkbar, dass die immunologische Reaktion eine Änderung des Verhaltens hervorruft, welche fälschlicherweise als therapeutische Reaktion fehlgedeutet werden könnte bzw. diese verfälscht. Im experimentellen Teil dieser Arbeit wurde C57/B6J-Mäusen wöchentlich 400µg IVIG über eine Dauer von 12 Wochen intraperitoneal injiziert. Es konnte eine signifikante MAHA-Reaktion auf das humane Immunglobulin G gemessen werden. Es kam zu einem signifikanten Anstieg der MAHA-Reaktion in Woche 9. Eine Änderung in grundlegendem Erkundungs- und Ängstlichkeitsverhalten sowie Kognition konnte nicht begleitend beobachtet werden. Hier belegen wir, dass die Behandlung von Mäusen mit IVIG zwar zu einer erhöhten MAHA-Reaktion ab Woche 10 führt jedoch ohne begleitende Änderung im Verhalten der Mäuse. Resultierend ist es möglich, pharmakologische und immunologische Aktivität sowie die therapeutische Effizienz von IVIG in Tiermodellen über eine Zeitspanne entsprechend unserer Versuchsdauer zu untersuchen. In diesem Zeitraum findet keine nachweisbare Beeinflussung oder Neutralisation therapeutischer Effekte von IVIG durch die MAHA-Reaktion statt.

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