Genetic evidence for the involvement of Fcgamma receptor III in experimental autoimmune myasthenia gravis pathogenesis

J Neuroimmunol. 2006 May;174(1-2):157-67. doi: 10.1016/j.jneuroim.2006.01.015. Epub 2006 Mar 9.

Abstract

Immune complexes and classical complement pathway play vital roles in experimental autoimmune myasthenia gravis (EAMG). To analyze the role of immune complex receptors in EAMG, FcgammaRIII knockout (KO) mice were immunized with AChR and were found out to be resistant to EAMG induction. This was associated with reduced neuromuscular junction deposits, lymph node cell (LNC) IL-6 production and serum complement levels. EAMG resistance of anti-C1q Ab-administered mice was also associated with reduced LNC IL-6 production and neuromuscular junction deposits, indicating C1q involvement in EAMG resistance. The data provide the first direct genetic evidence for Fcgamma receptor involvement in EAMG pathogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antigens, CD / metabolism
  • Complement C1q / immunology
  • Complement C1q / metabolism
  • Complement C3-C5 Convertases / metabolism
  • Complement Membrane Attack Complex / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Flow Cytometry / methods
  • Immunoglobulin G / metabolism
  • Immunohistochemistry / methods
  • Interleukin-6 / metabolism
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / physiopathology
  • Myasthenia Gravis, Autoimmune, Experimental / chemically induced
  • Myasthenia Gravis, Autoimmune, Experimental / genetics*
  • Myasthenia Gravis, Autoimmune, Experimental / pathology*
  • Myasthenia Gravis, Autoimmune, Experimental / physiopathology
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / pathology
  • Radioimmunoassay / methods
  • Receptors, IgG / deficiency
  • Receptors, IgG / genetics
  • Receptors, IgG / physiology*
  • Receptors, Nicotinic / genetics
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Antibodies
  • Antigens, CD
  • Complement Membrane Attack Complex
  • Fcgr3 protein, mouse
  • Immunoglobulin G
  • Interleukin-6
  • Receptors, IgG
  • Receptors, Nicotinic
  • Complement C1q
  • Complement C3-C5 Convertases