Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis
Objectives. Interferon-β (IFN-β) is used in the treatment of multiple sclerosis (MS). IFN-β activation of signal transduction and activation of transcription (STAT)-4 is linked to its immunomodulatory effects. Previous studies suggest a type I IFN deficit in immune cells of MS patients, but data on...
| Main Authors: | , , , |
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| Format: | Article |
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Wiley
2016
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| Online Access: | https://eprints.nottingham.ac.uk/40258/ |
| _version_ | 1848796018920914944 |
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| author | Tanasescu, Radu Midgley, Angela Robins, R. Adrian Constantinescu, Cris S. |
| author_facet | Tanasescu, Radu Midgley, Angela Robins, R. Adrian Constantinescu, Cris S. |
| author_sort | Tanasescu, Radu |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Objectives. Interferon-β (IFN-β) is used in the treatment of multiple sclerosis (MS). IFN-β activation of signal transduction and activation of transcription (STAT)-4 is linked to its immunomodulatory effects. Previous studies suggest a type I IFN deficit in immune cells of MS patients, but data on interferon-α/β receptor (IFNAR) expression and the relationship with treatment response are conflicting. Here we compare IFN-β-mediated STAT4 activation in immune cells of untreated MS patients and controls.
Materials & methods. Peripheral blood mononuclear cells (PBMC) from 27 untreated patients with relapsing MS, obtained before the initiation of IFN-β treatment, and 12 matched controls were treated in vitro with IFN-β. Total and phosphorylated STAT4 (pSTAT4) and IFNAR were measured by flow cytometry and quantitative PCR. The patients were followed-up for 5 years.
Results. pSTAT4 induction by IFN-β was lower in MS patients than in controls, as was expression of IFNAR. pSTAT4 expression did not correlate with the clinical outcome at five years, measured by EDSS change. There was a negative correlation between the baseline IFNAR1 mRNA levels and relapse rate.
Conclusions. The results suggest decreased IFN-β responsiveness in MS patients, associated with reduced STAT4 activation and reduced IFNAR expression. This reduced responsiveness does not appear to affect the long term clinical outcome of IFN-β treatment. |
| first_indexed | 2025-11-14T19:41:19Z |
| format | Article |
| id | nottingham-40258 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:41:19Z |
| publishDate | 2016 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-402582020-05-04T18:27:34Z https://eprints.nottingham.ac.uk/40258/ Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis Tanasescu, Radu Midgley, Angela Robins, R. Adrian Constantinescu, Cris S. Objectives. Interferon-β (IFN-β) is used in the treatment of multiple sclerosis (MS). IFN-β activation of signal transduction and activation of transcription (STAT)-4 is linked to its immunomodulatory effects. Previous studies suggest a type I IFN deficit in immune cells of MS patients, but data on interferon-α/β receptor (IFNAR) expression and the relationship with treatment response are conflicting. Here we compare IFN-β-mediated STAT4 activation in immune cells of untreated MS patients and controls. Materials & methods. Peripheral blood mononuclear cells (PBMC) from 27 untreated patients with relapsing MS, obtained before the initiation of IFN-β treatment, and 12 matched controls were treated in vitro with IFN-β. Total and phosphorylated STAT4 (pSTAT4) and IFNAR were measured by flow cytometry and quantitative PCR. The patients were followed-up for 5 years. Results. pSTAT4 induction by IFN-β was lower in MS patients than in controls, as was expression of IFNAR. pSTAT4 expression did not correlate with the clinical outcome at five years, measured by EDSS change. There was a negative correlation between the baseline IFNAR1 mRNA levels and relapse rate. Conclusions. The results suggest decreased IFN-β responsiveness in MS patients, associated with reduced STAT4 activation and reduced IFNAR expression. This reduced responsiveness does not appear to affect the long term clinical outcome of IFN-β treatment. Wiley 2016-12-05 Article PeerReviewed Tanasescu, Radu, Midgley, Angela, Robins, R. Adrian and Constantinescu, Cris S. (2016) Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis. Acta Neurologica Scandinavica . ISSN 1600-0404 http://onlinelibrary.wiley.com/doi/10.1111/ane.12715/full doi:10.1111/ane.12715 doi:10.1111/ane.12715 |
| spellingShingle | Tanasescu, Radu Midgley, Angela Robins, R. Adrian Constantinescu, Cris S. Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis |
| title | Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis |
| title_full | Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis |
| title_fullStr | Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis |
| title_full_unstemmed | Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis |
| title_short | Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis |
| title_sort | decreased interferon-β induced stat-4 activation in immune cells and clinical outcome in multiple sclerosis |
| url | https://eprints.nottingham.ac.uk/40258/ https://eprints.nottingham.ac.uk/40258/ https://eprints.nottingham.ac.uk/40258/ |