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

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands laura.vandervoort{at}vumc.nl

A Kok

Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands

A Visser

CBM Oudejans

Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands

M Caldano

Centro di Rifermento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

F Gilli

Centro di Rifermento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

A Bertolotto

Centro di Rifermento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

CH Polman

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands

J Killestein

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands

Background

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

Objectives

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

Methods

In 79 MS patients MxA mRNA expression was determined 4 hours after IFNβ 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 NAβ 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 IFNβ bioactivity, emphasizing the need of a pre-injection sample.

Conclusions

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

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

This version was published on February 1, 2009

Multiple Sclerosis, Vol. 15, No. 2, 212-218 (2009)
DOI: 10.1177/1352458508096877


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