IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice

Ruksana Huda, Richard T. Strait, Erdem Tüzün, Fred D. Finkelman, Premkumar Christadoss

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to neuromuscular junction (NMJ) damage by anti-acetylcholine receptor (AChR) auto-antibodies and complement. In experimental autoimmune myasthenia gravis (EAMG), which is induced by immunization with Torpedo AChR in CFA, anti-AChR IgG2b and IgG1 are the predominant isotypes in the circulation. Complement activation by isotypes such as IgG2b plays a crucial role in EAMG pathogenesis; this suggested the possibility that IgG1, which does not activate complement through the classical pathway, may suppress EAMG. In this study, we show that AChR-immunized BALB/c mice genetically deficient for IgG1 produce higher levels of complement-activating isotypes of anti-AChR, especially IgG3 and IgG2a, and develop increased IgG3/IgG2a deposits at the NMJ, as compared to wild type (WT) BALB/c mice. Consistent with this, AChR-immunized IgG1<sup>-/-</sup> BALB/c mice lose muscle strength and muscle AChR to a greater extent than AChR-immunized WT mice. These observations demonstrate that IgG1 deficiency leads to increased severity of EAMG associated with an increase in complement activating IgG isotypes. Further studies are needed to dissect the specific role or mechanism of IgG1 in limiting EAMG and that of EAMG exacerbating role of complement activating IgG3 and IgG2a in IgG1 deficiency.

Original languageEnglish (US)
Pages (from-to)68-72
Number of pages5
JournalJournal of Neuroimmunology
Volume281
DOIs
StatePublished - Apr 15 2015

Fingerprint

Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
Immunoglobulin G
Neuromuscular Junction
Classical Complement Pathway
Torpedo
Complement Activation
Myasthenia Gravis
Muscle Weakness
Muscle Strength
Autoimmune Diseases
Immunization

Keywords

  • Acetylcholine receptor
  • Autoimmunity
  • Experimental autoimmune myasthenia gravis
  • IgG1
  • IgG3
  • Myasthenia gravis

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice. / Huda, Ruksana; Strait, Richard T.; Tüzün, Erdem; Finkelman, Fred D.; Christadoss, Premkumar.

In: Journal of Neuroimmunology, Vol. 281, 15.04.2015, p. 68-72.

Research output: Contribution to journalArticle

Huda, Ruksana ; Strait, Richard T. ; Tüzün, Erdem ; Finkelman, Fred D. ; Christadoss, Premkumar. / IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice. In: Journal of Neuroimmunology. 2015 ; Vol. 281. pp. 68-72.
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