4.6 Article

Neuromyelitis optica: Passive transfer to rats by human immunoglobulin

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.06.085

Keywords

Neuromyelitis optica; Aquaporin-4; Astrocyte; Passive transfer; Complement; Multiple sclerosis; Animal model; Experimental autoimmune encephalomyelitis

Funding

  1. National Institute of Biomedical Innovation (NIBIO)
  2. Ministry of Health, Labour and Welfare of Japan

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Recurrent attacks of optic neuritis and myelitis are the hallmarks of both neuromyelitis optica (NMO) and multiple sclerosis (MS). NMO immunoglobulin G (NMO-IgG), which recognizes astrocytic aquaporin-4 (AQP4) water channels, is a specific serum autoantibody that distinguishes NMO from MS. The pathogenic role of the anti-AQP4 antibody (AQP4-Ab, NMO-IgG) in NMO has been speculated based on several studies in vitro. The aim of this study was to demonstrate the pathogenicity of AQP4-Ab in vivo. We obtained IgG from patients who underwent therapeutic plasmapheresis, and developed an animal model by passive transfer of IgG to rats. The active lesions of the rats exhibited pathological characteristics strikingly similar to those of NMO, marked by astrocytic loss and perivascular deposition of immunoglobulin and complements. These findings provide the first evidence of the pathogenicity of AQP4-Ab in vivo and support the therapeutic efficacy of eliminating the antibodies by plasmapheresis. (C) 2009 Elsevier Inc. All rights reserved.

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