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: Makoto Kinoshita, Yuji Nakatsuji, Masayuki Moriya, Tatsusada Okuno, Atsushi Kumanogoh, Misa Nakano, Toshiyuki Takahashi, Kazuo Fujihara, Keiko Tanaka, Saburo Sakoda
• Journal: Neuroreport (Neuroreport) Vol. 20 Issue 5 Pg. 508-12 (Mar 25 2009) ISSN: 1473-558X [Electronic] England
• PMID: 19297740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AQP4 protein, human
• Aquaporin 4
• Autoantibodies
• Immunoglobulins
• RNA, Small Interfering

Topics

• Analysis of Variance
• Animals
• Apoptosis
• Aquaporin 4 (immunology, metabolism)
• Astrocytes (physiology)
• Autoantibodies (blood, immunology)
• Cell Count
• Cell Survival (physiology)
• Cells, Cultured
• Down-Regulation
• Humans
• Immunoglobulins (immunology, metabolism)
• Immunohistochemistry
• Necrosis
• Neuromyelitis Optica (immunology)
• RNA, Small Interfering (metabolism)
• Rats
• Rats, Sprague-Dawley