Publikationsserver der Universitätsbibliothek Marburg
Titel:Immunologische Pathomechanismen bei Spättypallergie auf Betalactamantibiotika
Autor:Schäfer, Carolin
Weitere Beteiligte: Pfützner, W. (Prof. Dr. med.)
Veröffentlicht:2016
URI:https://archiv.ub.uni-marburg.de/diss/z2016/0303
URN: urn:nbn:de:hebis:04-z2016-03036
DOI: https://doi.org/10.17192/z2016.0303
DDC:610 Medizin
Titel (trans.):immunological pathomechanism in case of delayed type hypersensitivity of betalacatam antibiotics
Publikationsdatum:2016-04-20
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Elispot, Hypersensibilität, delayed type, allergy, Elispot assay, Allergologie, Penicilline, Allergie, Betalactamantibiotika, Pathomechanismus, Spättypallergie, betalactam antibiotics

Zusammenfassung:
Die Entwicklung von Allergien ist auf das komplexe Zusammenspiel zwischen genetischen Faktoren und bestimmten Umwelteinflüssen zurückzuführen. Bei etwa 25% der Menschen entwickeln sich überschießende Immunantworten, die durch harmlose Umweltstoffe wie Pollen oder Nahrungsmittel aber auch Arzneimittel ausgelöst werden können. Die Arzneimittelallergie hat in den letzten Jahren stetig an Bedeutung zugenommen. Hierbei kommt es zu einer immunologisch vermittelten Überempfindlichkeit auf ein Medikament, die sich nach den zugrunde liegenden Pathomechanismen als allergische Soforttypreaktion oder als Spättypreaktion nach Coombs und Gell äußern kann. Die Betalactmantibiotika gehören zu den häufigsten Auslösern allergischer Medikamentenreaktionen. Der Pathomechanismus einer Soforttypreaktion auf Penicilline entspricht einer klassischen IgE-vermittelten Reaktion. Demgegenüber steht die Spättypreaktion, bei der es zur Aktivierung spezifischer T-Lymphozyten und zur Sekretion proinflammatorischer Zytokine kommt, durch die schließlich die entsprechenden Hautreaktion in Form eines Exanthems hervorgerufen wird. Die vorliegende Studie wurde mit vier unterschiedlichen Probandengruppen durchgeführt, bei denen Untersuchungen mit verschiedenen Betalactamantibiotika (Penicillin G, Amoxicillin, Ampicillin und Cefuroxim) durchgeführt wurden. Im Fokus der Studie standen dabei Allergiker vom Spättyp. Diese wurden klinisch und immunologisch mit Kollektiven von Soforttypallergikern sowie von nicht-allergischen Individuen mit und ohne Betalactamexposition als Kontrollgruppen verglichen. Zu diesem Zweck wurden allergologische In-vivo-Testverfahren wie Hauttests (Prick-, Intrakutan-, Epikutantest) und die orale Provokationstestung durchgeführt. Auf Basis der hierbei gewonnenen Ergebnisse erfolgte neben der Anamnese die klinische Charakterisierung und Einteilung in die vorab festgelegten Probandengruppen. Durch die anschließenden Verfahren der In-vitro-Diagnostik wurden sowohl allergenspezifische Antikörper im Serum als auch die Frequenzen allergenspezifischer T-Zellpopulationen im peripheren Blut anhand Zell-spezifischer Markerzytokine (IFN-γ, IL-5 und IL-10) bestimmt. Zusätzlich wurde die Frequenz regulatorischer T(reg)-Zellen anhand des Oberflächenmarkerprofils CD4+CD25+CD127low untersucht. Die hierbei ermittelten immunologischen Parameter der Spättypallergiker wurden mit denen der anderen Studienkollektive verglichen. Die Studienergebnisse zeigten eine unauffällige humorale Antwort im Vergleich der vier verschiedenen Probandengruppen. Auf zellulärer Ebene konnte das Kollektiv der Spättypallergiker nicht über die häufig postulierte vermehrte IFN-γ-Sekretion von den anderen drei Patientengruppen abgegrenzt werden, jedoch fand sich eine gesteigerte Th2-Zellantwort bei den Soforttypallergikern. Es ließen sich keine Unterschiede der Anzahl IL-10-sezernierender Tr1-Zellen nach In-vitro-Betalactamstimulation in allen vier Gruppen detektieren, allerdings zeigte sich in der mit Betalactamantibiotika behandelten Kontrollgruppe ein tendenzieller Anstieg von IFN-γ+ und IL-10+ T-Zellen. Dies könnte ein Hinweis für die Induktion eines protektiven Mechanismus bei gesunden Probanden nach Antibiotikastimulation sein. Andererseits fand sich eine tendenzielle Abnahme der CD4+CD25+CD127low Treg-Population in dieser Kontrollgruppe während der dreitägigen systemischen Betalactamtherapie, was die Komplexität möglicher immunologischer Reaktionsmechanismen auf Betalaktamantibiotika unterstreicht. Insofern liefern die Ergebnisse der vorliegenden Arbeit einige interessante Ansatzpunkte für weitere wissenschaftliche Untersuchungen zu dem insgesamt noch sehr wenig erforschten Gebiet der Arzneimittelallergie.

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