MxA mRNA decrease preceding NAb detection in IFNβ-treated MS patients

Abstract

Background: Multiple sclerosis (MS) patients treated with interferon beta (IFNβ) are at risk of a declining response to treatment because of the production of IFNβ-neutralizing antibodies (NAbs). The expression of Myxovirus resistance protein A (MxA) mRNA is regarded as a marker of IFNβ bioactivity. Aims: The aim of this study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its relationship to NAb production. Methods: A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNβ treatment. NAbs and MxA mRNA were monitored every six months. Results: 119 patients were consecutively enrolled and 107 were included in the final analysis. Both the presence of NAbs and a decrease in MxA mRNA below the cut off were revealed in 15 patients, however, in six patients (40%) positivity for NAbs was preceded by the decrease in MxA mRNA. In addition, a further six patients showing a decline in MxA mRNA did not have detectable NAbs. Conclusion: Our data indicate that quantification of MxA mRNA is a more sensitive identifier of loss of IFNβ efficacy than the NAb positivity.