MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK


Kucukerden M., Huda R., Tuzun E. , Yilmaz A., Skriapa L., Trakas N., ...More

JOURNAL OF NEUROIMMUNOLOGY, vol.295, pp.84-92, 2016 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 295
  • Publication Date: 2016
  • Doi Number: 10.1016/j.jneuroim.2016.04.003
  • Title of Journal : JOURNAL OF NEUROIMMUNOLOGY
  • Page Numbers: pp.84-92
  • Keywords: Myasthenia gravis, Experimental autoimmune myasthenia gravis, Muscle specific kinase, Anti-MuSK IgG, MuSK-binding B cell, MUSCLE-SPECIFIC KINASE, ACETYLCHOLINE-RECEPTORS, IMMUNIZED MICE, AUTOANTIBODIES, MECHANISMS, BINDING, MOUSE, MODEL, DYSFUNCTION, COMPLEMENT

Abstract

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 IgG1 +, IgG2 + and IgG3 + 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. (C) 2016 Elsevier B.V. All rights reserved.