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

Melike Küçükerden, Ruksana Huda, Erdem Tüzün, Abdullah Yilmaz, Lamprini Skriapa, Nikos Trakas, Richard T. Strait, Fred D. Finkelman, Sevil Kabadayi, Paraskevi Zisimopoulou, Socrates Tzartos, Premkumar Christadoss

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalJournal of Neuroimmunology
Volume295-296
DOIs
StatePublished - Jun 15 2016

Fingerprint

Autoimmune Experimental Myasthenia Gravis
Immunoglobulin G
Antibodies
Knockout Mice
Muscles
Phosphotransferases
Neuromuscular Junction
Myasthenia Gravis
Cholinergic Receptors
Serum
Immunoglobulins
Anti-Idiotypic Antibodies
Immunization

Keywords

  • Anti-MuSK IgG
  • Experimental autoimmune myasthenia gravis
  • Muscle specific kinase
  • MuSK-binding B cell
  • Myasthenia gravis

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Küçükerden, M., Huda, R., Tüzün, E., Yilmaz, A., Skriapa, L., Trakas, N., ... Christadoss, P. (2016). MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK. Journal of Neuroimmunology, 295-296, 84-92. https://doi.org/10.1016/j.jneuroim.2016.04.003

MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK. / Küçükerden, Melike; Huda, Ruksana; Tüzün, Erdem; Yilmaz, Abdullah; Skriapa, Lamprini; Trakas, Nikos; Strait, Richard T.; Finkelman, Fred D.; Kabadayi, Sevil; Zisimopoulou, Paraskevi; Tzartos, Socrates; Christadoss, Premkumar.

In: Journal of Neuroimmunology, Vol. 295-296, 15.06.2016, p. 84-92.

Research output: Contribution to journalArticle

Küçükerden, M, Huda, R, Tüzün, E, Yilmaz, A, Skriapa, L, Trakas, N, Strait, RT, Finkelman, FD, Kabadayi, S, Zisimopoulou, P, Tzartos, S & Christadoss, P 2016, 'MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK', Journal of Neuroimmunology, vol. 295-296, pp. 84-92. https://doi.org/10.1016/j.jneuroim.2016.04.003
Küçükerden, Melike ; Huda, Ruksana ; Tüzün, Erdem ; Yilmaz, Abdullah ; Skriapa, Lamprini ; Trakas, Nikos ; Strait, Richard T. ; Finkelman, Fred D. ; Kabadayi, Sevil ; Zisimopoulou, Paraskevi ; Tzartos, Socrates ; Christadoss, Premkumar. / MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK. In: Journal of Neuroimmunology. 2016 ; Vol. 295-296. pp. 84-92.
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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.",
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