Myasthenia gravis: a pathologic approach


  • J.S.J.M. Hounjet



Our immune system protects us from all kinds of pathogens our body faces every day. However, the immune system can also initiate an immune response against our own proteins. This is called autoimmunity. Myasthenia gravis (MG) is a rare autoimmune disease in which patients show severe muscle weakness, due to antibody production against proteins of the neuromuscular junction, which is the connection between nerve and muscle. At this moment, three different forms of myasthenia gravis are identified. Muscle-specific tyrosine kinase (MuSK)-MG is a form of MG in which patients produce antibodies, predominantly immunoglobulin (Ig)G4, against MuSK. This paper is a summary of a B cell immortalization project, in which antibodies produced by MuSK-MG patients are investigated. The aim of this study was to sequence and generate antibodies produced by these patients in vitro to learn more about the pathological mechanism of MuSK-MG. Blood-derived B cells of MuSK-MG patients were immortalized by the Epstein Bar Virus and stimulated to grow and produce antibodies in culture. Genes of these antibodies were amplified and analyzed. These amplification products were cloned in vectors and will be transfected in a human embryonic kidney (HEK)-cell line. This study showed that the B cell immortalization method worked and that MuSK-MG patients predominantly produce IgM antibodies against MuSK. This is very striking as literature states that these patients predominantly produce IgG4 against MuSK. It is suggested that this high production of IgM is due to the absence of the heavy chain isotype switch from IgM to IgG. Moreover, as the pathologic mechanism of MuSK-MG is still unknown, IgM may play an important pathological role.


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