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Published on: June 14, 2018
Interferon-beta bioactivity measurement in multiple sclerosis: feasibility for routine clinical practice
L F van der Voort1, A Kok, A Visser
1Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. laura.vandervoort@vumc.nl
Background:
Neutralising antibodies (NAb) to interferon beta (IFN beta) are associated with a reduced bioactivity and efficacy of IFN beta in multiple sclerosis (MS). Unclear is how to apply IFN beta bioactivity measurements (quantification of Myxovirus resistance protein A (MxA) mRNA) in clinical practice.
Objectives:
To evaluate value and feasibility of IFN beta bioactivity measurement with a single MxA mRNA measurement for screening and a second measurement before and after IFN beta administration for definite confirmation of IFN beta bioactivity status.
Methods:
In 79 MS patients MxA mRNA expression was determined 4 hours after IFN beta 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 beta 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 beta bioactivity, emphasizing the need of a pre-injection sample.
Conclusions:
Our data suggest that for IFN beta bioactivity screening a single post-injection measurement seems reasonable. However, MxA induction measurement based on both pre- and post-IFN beta injection samples at second measurement is somewhat more precise in determining ultimate IFN beta bioactivity status.
Insights
Measuring Myxovirus resistance protein A (MxA) mRNA helps assess interferon beta (IFN beta) bioactivity in multiple sclerosis (MS) patients. A single post-injection test is useful for screening, but pre- and post-injection measurements confirm bioactivity status more precisely.
Area of Science:
- Neuroimmunology
- Pharmacodynamics
- Biomarker Discovery
Background:
- Neutralizing antibodies (NAb) to interferon beta (IFN beta) reduce its efficacy in multiple sclerosis (MS).
- Clinical application of IFN beta bioactivity measurements, such as Myxovirus resistance protein A (MxA) mRNA quantification, remains unclear.
Purpose of the Study:
- To evaluate the value and feasibility of IFN beta bioactivity measurement using MxA mRNA.
- To establish a protocol for screening and confirming IFN beta bioactivity status in MS patients.
Main Methods:
- MxA mRNA expression was measured in 79 MS patients 4 hours post-IFN beta administration.
- A second measurement, comparing pre- and post-injection samples, was performed for inadequate responses to confirm bioactivity.
- MxA mRNA expression was correlated with NAb titres determined by cytopathic effect assay (CPE).
Main Results:
- NAb titres significantly correlated with MxA mRNA expression and induction.
- Only one patient showed adequate MxA mRNA expression with high NAb titres.
- Among biological non-responders, 81% had high-titre NAb; pre-injection samples were crucial for accurate bioactivity assessment.
Conclusions:
- A single post-injection MxA mRNA measurement is reasonable for IFN beta bioactivity screening.
- Measuring MxA induction using both pre- and post-IFN beta injection samples provides a more precise determination of IFN beta bioactivity status.
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