| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6019962 | Journal of Neuroimmunology | 2016 | 9 Pages |
Highlightâ¢Non-complement fixing isotype IgG1 is not essential for EAMG induction in mice.â¢Clinical severity of MuSK-EAMG is correlated with MuSK-reactive B cell levels.â¢Anti-MuSK IgG3 is the predominant isotype in MuSK induced EAMG.
Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1Â +, IgG2Â + and IgG3Â + peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis.
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