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J Neuroimmunol. 2008 Mar;195(1-2):151-6. doi: 10.1016/j.jneuroim.2008.01.013. Epub 2008 Apr 1.

Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1.

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Department of Neurology, J3-R 166, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.


We studied the longitudinal relation between disease severity and titers of antigen-specific IgG subclasses in sera of patients with myasthenia gravis and antibodies to Muscle Specific Kinase (MuSK MG). Six patients were included of whom 55 samples had been collected during 2.5-13.4 years. Anti-MuSK antibodies were determined by ELISA and with a cell-based immunofluorescence assay. Disease severity was scored on a semi continuous scale. Only antigen-specific IgG4, and not IgG1, titers were significantly associated with disease severity in a linear mixed effect model (p = 0.036). Levels of IgG4 antibodies were above IgG1 in all samples except in one patient who went into clinical remission while switching from IgG4 to IgG1. The results support an important role for IgG4 in the pathogenesis of MuSK MG, in contrast to MG with anti-acetylcholine receptor antibodies.

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