titoli, abstracts, parole chiave >>>
MxA mRNA quantification and disability progression in interferon beta-treated Multiple Sclerosis patients

Serana, Federico and Imberti, Luisa and Amato, Maria Pia and Comi, Giancarlo and Gasperini, Claudio and Ghezzi, Angelo and Martinelli, Vittorio and Provinciali, Leandro and Rottoli, Maria Rosa and Sotgiu, Stefano and Stecchi, Sergio and Vecchio, Michele and Zaffaroni, Mauro and Cordioli, Cinzia and Capra, Ruggero (2014) MxA mRNA quantification and disability progression in interferon beta-treated Multiple Sclerosis patients. PLoS One, Vol. 9 (4), e94794. eISSN 1932-6203. Article.

[img]
Preview
Full text disponibile come PDF Richiede visualizzatore di PDF come GSview, Xpdf o Adobe Acrobat Reader
Available under License Creative Commons Attribution.

547Kb

DOI: 10.1371/journal.pone.0094794

Abstract

Even though anti-interferon beta (IFNβ) antibodies are the main determinants of IFNβ bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNβ biological activity in IFNβ-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFNβ binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFNβ therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFNβ bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFNβ therapy.

Item Type:Article
ID Code:9763
Status:Published
Refereed:Yes
Uncontrolled Keywords:Anti-interferon beta (IFNβ) antibodies, Myxovirus-resistance protein A (MxA), multiple sclerosis patients
Subjects:Area 06 - Scienze mediche > MED/39 Neuropsichiatria infantile
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:Public Library of Science
eISSN:1932-6203
Copyright Holders:© 2014 Serana et al.
Deposited On:28 Apr 2014 09:46

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore

Repository Staff Only: item control page