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Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures
Author(s) -
Howe Charles L.,
Kaptzan Tatiana,
Magaña Setty M.,
AyersRingler Jennifer R.,
LaFranceCorey Reghann G.,
Lucchinetti Claudia F.
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22635
Subject(s) - neuromyelitis optica , astrocyte , aquaporin 4 , immunology , biology , multiple sclerosis , chemokine , inflammation , antigen , demyelinating disease , central nervous system , medicine , pathology , neuroscience
Neuromyelitis optica (NMO) is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin‐4 (AQP4) water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte‐enriched cultures and treatment with NMO patient‐derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin‐2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease‐specific, as serum from patients with relapsing–remitting multiple sclerosis, Sjögren's, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development. GLIA 2014;62:692–708

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