Guidelines for pre-clinical assessment of the acetylcholine receptor--specific passive transfer myasthenia gravis model-Recommendations for methods and experimental designs.
Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies.
Department of Pharmacology & Physiology, The George Washington University, Washington, DC, USA. Electronic address: lkusner@gwu.edu.
Linda L
LL
Kusner
Division Neuroscience, School for Mental Health and Neuroscience, Maastricht University, 6200 MD Maastricht, The Netherlands.
Mario
M
Losen
The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Angela
A
Vincent
Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA, USA.
Jon
J
Lindstrom
Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
Socrates
S
Tzartos
Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
Konstantinos
K
Lazaridis
Division Neuroscience, School for Mental Health and Neuroscience, Maastricht University, 6200 MD Maastricht, The Netherlands.
Pilar
P
Martinez-Martinez
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D017408:Guidelines as Topic; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D020720:Myasthenia Gravis, Autoimmune, Experimental; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D011950:Receptors, Cholinergic
Acetylcholine receptor antibody; Autoimmune disease; Myasthenia gravis; Neuromuscular junction; Passive transfer model