Decreased interferon-β induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis

Tanasescu, Radu and Midgley, Angela and 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

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Abstract

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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Clinical Neuroscience
Identification Number: https://doi.org/10.1111/ane.12715
Depositing User: Eprints, Support
Date Deposited: 02 Feb 2017 11:24
Last Modified: 20 Feb 2017 17:38
URI: http://eprints.nottingham.ac.uk/id/eprint/40258

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