Cytotoxic effect of neuromyelitis optica antibody (NMO-IgG) to astrocytes: an in vitro study

J Neuroimmunol. 2009 Oct 30;215(1-2):31-5. doi: 10.1016/j.jneuroim.2009.07.014. Epub 2009 Aug 19.


NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) that binds selectively to aquaporin-4 (AQ4), an astrocytic water channel. The normal distribution of AQP4 coincides with the sites of immunoglobulin and complement deposits in lesions found in autopsy studies. The underlying mechanisms of cytotoxicity by NMO-IgG on astrocytes are not well known. In this study we show that serum samples from seropositive NMO patients (21) induce a higher rate of cell death compared with sera from seronegative NMO (16), relapsing-remitting MS (20) patients, and healthy controls (24) on primary cultures of astrocytes. Similar results were obtained by two different techniques: lactate dehydrogenase release and tetrazolium-based viability assay. Cell death was only observed in the presence of active complement. The complement-dependent cytotoxicity was not accompanied by caspase-3/7 activation or increase in the percentage of apoptotic cells. Our data show that NMO-IgG induces a complement-dependent cytotoxicity of astrocytes in vitro, and suggest that a mechanism of cellular death by necrosis might be implicated in the pathophysiology of NMO.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies / blood
  • Antibodies / physiology*
  • Apoptosis / immunology
  • Astrocytes / immunology*
  • Cell Survival / immunology
  • Cells, Cultured
  • Complement System Proteins / physiology
  • Cytotoxicity, Immunologic / immunology*
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Neuromyelitis Optica / immunology*
  • Neuromyelitis Optica / pathology
  • Young Adult


  • Antibodies
  • Immunoglobulin G
  • Complement System Proteins