title: Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells.
abstract: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Anti-aquaporin-4 antibody (AQP4-Ab) is a highly specific serum autoantibody that is detected in patients with NMO. Several lines of evidence indicate that AQP4-Ab not only serves as a disease marker but also plays a pivotal role in the pathogenesis of NMO. Although the pathogenicity of AQP4-Ab in vivo has recently been demonstrated, the presence of CNS antigen-specific T cells is recognized as a prerequisite for the antibody to exert pathogenic effects. Thus, it remains unclear whether AQP4-Ab is the primary cause of the disease or a disease-modifying factor in NMO. Here we report that pre-treatment with complete Freund's adjuvant (CFA) alone is sufficient for AQP4-Ab to induce astrocytic damage in vivo. Our results show the primary pathogenic role of AQP4-Ab in the absence of CNS antigen-specific T cells, and suggest that danger signals provided by nonspecific inflammation can be a trigger for those who harbor the autoantibody to develop NMO.
authors.affiliation: Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakatsuji
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Moriya
authors.forename: Kazushiro
authors.initials: K
authors.lastname: Takata
authors.forename: Tatsusada
authors.initials: T
authors.lastname: Okuno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Koji
authors.initials: K
authors.lastname: Kajiyama
authors.forename: Hiroo
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005620:Freund's Adjuvant / Q000493:pharmacokinetics; D006801:Humans; D009471:Neuromyelitis Optica / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D005620:Freund's Adjuvant