Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 313, Issue 1-2, Pages 48-53Publisher
ELSEVIER
DOI: 10.1016/j.jns.2011.09.032
Keywords
NMO; MS; SLE; Interferon; STAT1; MxA
Categories
Funding
- Brain Research Foundation
- NIH [K08 AI083790, P30 DK42086]
- NIAID [AI071651]
- NIH CTSA
- CTSA [UL1 RR024999]
- Lupus Research Institute
- Alliance for Lupus Research Target Identification in Lupus Grant
- Arthritis National Research Foundation
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Objective: Neuromyelitis optica (NMO) is characterized by selective inflammation of the spinal cord and optic nerves but is distinct from multiple sclerosis (MS). Interferon (IFN)-beta mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-beta therapy in this highly active disease. In systemic lupus erythematosus (SLE), IFNs adversely affect disease activity. This study examines for the first time whether serum IFN-alpha/beta activity and IFN-beta-induced responses in peripheral blood mononuclear cells (MNC) are abnormally elevated in NMO, as they are in SLE, but contrast to low levels in MS. Methods: Serum type I IFN-alpha/beta activity was measured by a previously validated bioassay of 3 IFN-stimulated genes (RT-PCR sensitivity, 0.1 U/ml) rather than ELISA, which has lower sensitivity and specificity for measuring serum IENs. IFN responses in PBMNC were assessed by in vitro IFN-beta-induced activation of phospho-tyrosine-STAT1 and phospho-serine-STAT1 transcription factors, and MxA proteins using Western blots. Results: Serum IFN-alpha/beta activity was highest in SLE patients, followed by healthy subjects and NMO, but was surprisingly low in therapy-nave MS. In functional assays in vitro, IFN-beta-induced high levels of P-S-STAT1 in NMO and SLE, but not in MS and controls. IFN-beta-induced MxA protein levels were elevated in NMO and SLE compared to MS. Conclusions: Serum IFN activity and IFN-beta-induced responses in PBMNC are elevated in SLE and NMO patients versus MS. This argues for similarities in pathophysiology between NMO and SLE and provides an explanation for IFN-induced disease worsening in NMO. (C) 2011 Elsevier B.V. All rights reserved.
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