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

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.