Morphological effects of myasthenia gravis patient sera on human muscle cells.
Myasthenia gravis (MG) is caused primarily by autoantibodies against the nicotinic acetylcholine receptor (AChR), but autoantibodies to other muscle proteins may be present. Many of these proteins have structural or signalling functions, the disruption of which may affect muscle cell morphology or viability. In order to investigate the role of such autoantibodies in MG, we examined the effect of MG patient sera, of different autoantibody composition and obtained at different stages of disease severity, on primary human muscle cells. Sera from MG patients induced changes in cell morphology from typical elongated cells to an irregular phenotype, caused the formation of inclusion bodies and intracellular vesicles, and led to a disordered arrangement of actin microfilaments. Sera from the most severely affected patients also induced cell death, which did not occur via classic apoptosis. The effects were not complement-mediated and were dose- and time-dependent. As the effects observed in the cell culture system correlated with disease severity, a greater understanding of the individual factors responsible for these effects may improve our understanding of MG pathogenesis and be of value in the assessment of disease in individual patients.
Luckman
Steven Paul
SP
Institute of Clinical Medicine, Section for Neurology, University of Bergen and Haukeland University Hospital, N5021 Bergen, Norway. steven.paul.luckman@helse-bergen.no
Skeie
Geir Olve
GO
Helgeland
Geir
G
Gilhus
Nils Erik
NE
D001323:Autoantibodies / Q000097:blood; D016923:Cell Death; D006801:Humans; D007106:Immune Sera / Q000633:toxicity*; D032342:Muscle Cells / Q000187:drug effects / Q000473:pathology*; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D007106:Immune Sera