Type I interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis.
J Neurol Sci
; 313(1-2): 48-53, 2012 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-22036215
ABSTRACT
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)-ß mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-ß 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-α/ß activity and IFN-ß-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-α/ß 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 IFNs. IFN responses in PBMNC were assessed by in vitro IFN-ß-induced activation of phospho-tyrosine-STAT1 and phospho-serine-STAT1 transcription factors, and MxA proteins using Western blots.RESULTS:
Serum IFN-α/ß activity was highest in SLE patients, followed by healthy subjects and NMO, but was surprisingly low in therapy-naïve MS. In functional assays in vitro, IFN-ß-induced high levels of P-S-STAT1 in NMO and SLE, but not in MS and controls. IFN-ß-induced MxA protein levels were elevated in NMO and SLE compared to MS.CONCLUSIONS:
Serum IFN activity and IFN-ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon Tipo I
/
Neuromielite Óptica
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Esclerose Múltipla Recidivante-Remitente
/
Lúpus Eritematoso Sistêmico
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article