Recombinant Acetylcholine Receptor Immunization Induces a Robust Model of Experimental Autoimmune Myasthenia Gravis in Mice
Lukas Theissen,
Christina B. Schroeter,
Niklas Huntemann,
Saskia Räuber,
Vera Dobelmann,
Derya Cengiz,
Alexander Herrmann,
Kathrin Koch-Hölsken,
Norbert Gerdes,
Hao Hu,
Philipp Mourikis,
Amin Polzin,
Malte Kelm,
Hans-Peter Hartung,
Sven G. Meuth,
Christopher Nelke,
Tobias Ruck
Affiliations
Lukas Theissen
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Christina B. Schroeter
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Niklas Huntemann
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Saskia Räuber
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Vera Dobelmann
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Derya Cengiz
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Alexander Herrmann
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Kathrin Koch-Hölsken
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Norbert Gerdes
Department of Cardiology, Pulmonolgy and Vascular Medicine, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Hao Hu
Department of Cardiology, Pulmonolgy and Vascular Medicine, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Philipp Mourikis
Department of Cardiology, Pulmonolgy and Vascular Medicine, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Amin Polzin
Department of Cardiology, Pulmonolgy and Vascular Medicine, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Malte Kelm
Department of Cardiology, Pulmonolgy and Vascular Medicine, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Hans-Peter Hartung
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Sven G. Meuth
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Christopher Nelke
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Tobias Ruck
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Myasthenia gravis (MG) is a prototypical autoimmune disease of the neuromuscular junction (NMJ). The study of the underlying pathophysiology has provided novel insights into the interplay of autoantibodies and complement-mediated tissue damage. Experimental autoimmune myasthenia gravis (EAMG) emerged as a valuable animal model, designed to gain further insight and to test novel therapeutic approaches for MG. However, the availability of native acetylcholine receptor (AChR) protein is limited favouring the use of recombinant proteins. To provide a simplified platform for the study of MG, we established a model of EAMG using a recombinant protein containing the immunogenic sequence of AChR in mice. This model recapitulates key features of EAMG, including fatigable muscle weakness, the presence of anti-AChR-antibodies, and engagement of the NMJ by complement and a reduced NMJ density. Further characterization of this model demonstrated a prominent B cell immunopathology supported by T follicular helper cells. Taken together, the herein-presented EAMG model may be a valuable tool for the study of MG pathophysiology and the pre-clinical testing of therapeutic applications.
