title: Astrocytic necrosis is induced by anti-aquaporin-4 antibody-positive serum.
abstract: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system, and humoral immunity is suggested to play an important role in the pathogenesis. The identification of an anti-aquaporin-4 antibody (AQP4-Ab, neuromyelitis optica immunoglobulin G) in the sera of patients with NMO has led to the investigation on the pathogenicity of the autoantibody. Recent immunohistological analyses revealed the primary loss of AQP4 on astrocytes and complement deposition in active lesions of NMO. In this report, we show that astrocytes are susceptible to sera from AQP4-Ab-positive patients and undergo necrosis in a complement-dependent manner. Our results suggest the primary pathogenic role of AQP4-Ab in NMO.
authors.affiliation: Departments of Neurology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakatsuji
authors.forename: Masayuki
authors.initials: M
authors.lastname: Moriya
authors.forename: Tatsusada
authors.initials: T
authors.lastname: Okuno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Misa
authors.initials: M
authors.lastname: Nakano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D051401:Aquaporin 4 / Q000276:immunology* / Q000378:metabolism; D001253:Astrocytes / Q000502:physiology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D009336:Necrosis; D009471:Neuromyelitis Optica / Q000276:immunology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D007136:Immunoglobulins; D034741:RNA, Small Interfering