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Pathophysiologie antikörperassoziierter ZNS-Erkrankungen

Pathophysiology of antibody-associated diseases of the central nervous system

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Zusammenfassung

Antikörper gegen intrazelluläre Antigene sind seit den 1980er/1990er Jahren bekannt. Die in den letzten Jahren entdeckten Antikörper gegen Oberflächenantigene sind aber in zweierlei Hinsicht „interessanter“ als jene: Sie verheißen ein besseres Ansprechen auf Immuntherapien und sie sind vermutlich selbst pathogen, was die Krankheitsmechanismen verstehen hilft. Dabei gibt es einerseits destruktive, irreversible Effekte der Antikörper gegen mit spannungsabhängigen Kaliumkanälen komplexierte Antigene (VGKC-Komplex-Antikörper, und zwar Antikörper gegen „leucine-rich glioma inactivated 1“ [LGI1]), andererseits reversible, funktionelle Wirkungen (wie z. B. bei den Antikörpern gegen den N-Methyl-D-Aspartat-Rezeptor, die zu einer Internalisierung dieser Rezeptoren, nicht aber zu einer Zellzerstörung führen; aber auch LGI1-Antikörper scheinen funktionelle, epileptogene Effekte zu erzeugen). Diese sich entwickelnden Erkenntnisse machen plausibel, warum antikörpersenkende Therapien Chancen auf eine Wiederherstellung der Gesundheit bei betroffenen Patienten bieten.

Summary

Antibodies against intracellular antigens have been known since the 1980s and 1990s but in recent years antibodies against surface antigens have also been discovered. These are “more interesting” than those to intracellular targets in two respects: they result in a better response to immunotherapy and are probably directly pathogenic, which helps to understand the disease mechanisms. There are the destructive and irreversible effects of the antibodies to antigens that are complexed with voltage-gated potassium channels (VGKC complex antibodies), especially antibodies to leucine-rich glioma inactivated 1 (LGI1) on the one hand. On the other hand, antibodies may have reversible functional effects, such as antibodies against the N-methyl-D-aspartate receptor, which cause an internalization of these receptors but do not lead to cell destruction: LGI1 antibodies also seem to have functional, in this case epileptogenic effects. These emerging findings make plausible why antibody-reducing therapies provide opportunities for the restoration of health in affected patients.

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Interessenkonflikt

Der korrespondierende Autor weist für sich und seine Koautoren auf folgende Beziehungen hin: C.G. Bien führt im Labor seiner Klinik Serum- und Liquordiagnostik bezüglich der im Text beschriebenen Antikörper durch. Für diese Diagnostik rechnet seine Klinik mit auswärtigen Einsendern Gebühren ab. C.G. Bien erhielt Reisekostenunterstützung von folgenden Firmen: Eisai, UCB, Desitin, Grifols; Vortragshonorare von folgenden Firmen: Eisai, UCB, GlaxoSmithKline, Desitin; Honorare für Mitarbeit in Advisory Boards der folgenden Firmen: UCB, Eisai.

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  1. Epilepsie-Zentrum Bethel, Krankenhaus Mara, Maraweg 17-21, 33617, Bielefeld, Deutschland

    C.G. Bien

  2. Zentrum für Hirnforschung, Medizinische Universität Wien, Wien, Deutschland

    J. Bauer

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  1. C.G. Bien
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  2. J. Bauer
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Correspondence to C.G. Bien.

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Bien, C., Bauer, J. Pathophysiologie antikörperassoziierter ZNS-Erkrankungen. Nervenarzt 84, 466–470 (2013). https://doi.org/10.1007/s00115-012-3606-6

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  • DOI: https://doi.org/10.1007/s00115-012-3606-6

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