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Interferon- bioactivity measurement in multiple sclerosis: feasibility for routine clinical practice

¹ Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
² Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
³ Centro di Rifermento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

^* To whom correspondence should be addressed.

	Abstract

Background

Neutralising antibodies (NAb) to interferon beta (IFN) are associated with a reduced bioactivity and efficacy of IFN in multiple sclerosis (MS). Unclear is how to apply IFN bioactivity measurements (quantification of Myxovirus resistance protein A (MxA) mRNA) in clinical practice.

Objectives

To evaluate value and feasibility of IFN bioactivity measurement with a single MxA mRNA measurement for screening and a second measurement before and after IFN administration for definite confirmation of IFN bioactivity status.

Methods

In 79 MS patients MxA mRNA expression was determined 4 hours after IFN administration. If inadequate, MxA mRNA expression testing was repeated 3 months afterwards, comparing post- and pre injection samples to determine whether IFNb bioactivity was persistently lacking. MxA mRNA expression was compared to NA titres, determined by the cytopathic effect assay (CPE).

Results

NAb titres correlated significantly with MxA mRNA expression and MxA mRNA induction. Of all screened patients, only one patient had adequate MxA mRNA expression and high NAb titres simultaneously. Of the biological non-responders at second measurement (21/55), 17 (81%) were high-titre NAb positive, 1 (5%) was low-titre NAb positive and 3 (14%) were NAb negative. Without considering the pre-injection measurement, two more NAb negative patients would have tested negative for IFN bioactivity, emphasizing the need of a pre-injection sample.

Conclusions

Our data suggest that for IFN bioactivity screening a single post-injection measurement seems reasonable. However, MxA induction measurement based on both pre- and post-IFN injection samples at second measurement is somewhat more precise in determining ultimate IFN bioactivity status.

Key Words: bioactivity, clinical practice, immune modulating therapy, interferon , multiple sclerosis, neutralising antibodies

First published on September 19, 2008, doi:10.1177/1352458508096877

Multiple Sclerosis 2009;15:212.

A more recent version of this article appeared on February 1, 2009


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