Neutralizing Antibodies to Interferon-β in Multiple Sclerosis
Interferon-β is an established and important immunomodulatory drug employed in the treatment of multiple sclerosis (MS). A significant proportion (~30%) of patients receiving interferon-β treatments develop drug-induced antibodies, which bind to the drug but do not necessarily block biological activity. However, a large proportion of this subgroup of patients (~80%) come to produce neutralizing antibodies (NAbs), which do reduce drug efficacy when present at high levels.
Anti-IFN-β NAb Testing by Cell-Based Assay (CBA)
Patient sera are screened for NAb positivity via a cell line transfected with the IFI-161 promoter linked to a luciferase reporter. If NAbs are not present, the luciferase substrate will illuminate. A positive result of NAb presence yields reduced illumination, which can be quantified in Tenfold Reduction Units (TRU)/mL and categorized into tiers of low, medium, and high antibody titres. Persistently high Ab titres signify poor therapeutic efficacy, and indicate the need for an alternate therapeutic strategy.