Type i interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis

Xuan Feng, Nicholas P. Reder, Mounica Yanamandala, Addie Hill, Beverly S. Franek, Timothy B. Niewold, Anthony T. Reder, Adil Javed

Research output: Contribution to journalArticle

38 Citations (Scopus)

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)-β mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-β 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/β activity and IFN-β-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/β 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-β-induced activation of phospho-tyrosine-STAT1 and phospho-serine-STAT1 transcription factors, and MxA proteins using Western blots. Results: Serum IFN-α/β 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-β-induced high levels of P-S-STAT1 in NMO and SLE, but not in MS and controls. IFN-β-induced MxA protein levels were elevated in NMO and SLE compared to MS. Conclusions: Serum IFN activity and IFN-β-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.

Original languageEnglish (US)
Pages (from-to)48-53
Number of pages6
JournalJournal of the Neurological Sciences
Volume313
Issue number1-2
DOIs
StatePublished - Feb 15 2012
Externally publishedYes

Fingerprint

Neuromyelitis Optica
Interferons
Multiple Sclerosis
Systemic Lupus Erythematosus
Serum
STAT1 Transcription Factor
Spinal Nerves
Interferon Type I
Optic Nerve
Biological Assay
Serine

Keywords

  • Interferon
  • MS
  • MxA
  • NMO
  • SLE
  • STAT1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Feng, X., Reder, N. P., Yanamandala, M., Hill, A., Franek, B. S., Niewold, T. B., ... Javed, A. (2012). Type i interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis. Journal of the Neurological Sciences, 313(1-2), 48-53. https://doi.org/10.1016/j.jns.2011.09.032

Type i interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis. / Feng, Xuan; Reder, Nicholas P.; Yanamandala, Mounica; Hill, Addie; Franek, Beverly S.; Niewold, Timothy B.; Reder, Anthony T.; Javed, Adil.

In: Journal of the Neurological Sciences, Vol. 313, No. 1-2, 15.02.2012, p. 48-53.

Research output: Contribution to journalArticle

Feng, X, Reder, NP, Yanamandala, M, Hill, A, Franek, BS, Niewold, TB, Reder, AT & Javed, A 2012, 'Type i interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis', Journal of the Neurological Sciences, vol. 313, no. 1-2, pp. 48-53. https://doi.org/10.1016/j.jns.2011.09.032
Feng, Xuan ; Reder, Nicholas P. ; Yanamandala, Mounica ; Hill, Addie ; Franek, Beverly S. ; Niewold, Timothy B. ; Reder, Anthony T. ; Javed, Adil. / Type i interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis. In: Journal of the Neurological Sciences. 2012 ; Vol. 313, No. 1-2. pp. 48-53.
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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)-β mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-β 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/β activity and IFN-β-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/β 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-β-induced activation of phospho-tyrosine-STAT1 and phospho-serine-STAT1 transcription factors, and MxA proteins using Western blots. Results: Serum IFN-α/β activity was highest in SLE patients, followed by healthy subjects and NMO, but was surprisingly low in therapy-na{\"i}ve MS. In functional assays in vitro, IFN-β-induced high levels of P-S-STAT1 in NMO and SLE, but not in MS and controls. IFN-β-induced MxA protein levels were elevated in NMO and SLE compared to MS. Conclusions: Serum IFN activity and IFN-β-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.",
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