Measurement of neutralizing antibodies to interferon beta in patients with multiple sclerosis

Treatment of multiple sclerosis (MS) with interferon beta (IFNβ) can be associated with the development of binding antibodies (BAbs) and neutralizing antibodies (NAbs). NAbs are a subset of BAbs that prevent IFNβ from effectively binding to or activating its receptor, thereby blocking its biologic effects and inhibiting its therapeutic effects. Several factors can affect the incidence and titers of NAbs that develop to IFNβ, including the type of IFNβ preparation used for treatment. One of the major limitations to evaluating the relative importance of these factors is the variation in assays used to detect IFNβ antibodies. Two major types of assays are used to detect antibodies to IFNβs: [1] binding assays, which measure the ability of antibodies in patients’ sera to bind to IFNβ; and [2] neutralization assays (or bioassays), which measure the ability of patients’ sera to neutralize the biologic effects of IFNβ. Assays used to detect NAbs differ in their sensitivity and specificity, and there can be high variability between laboratories in how these assays are performed (e. g., types of cells, quantity of IFNβ). This article reviews assays currently used for detecting NAbs to IFNβ and discusses the development of an international standard NAb assay. The myxovirus resistance protein A (MxA) assay is recommended as the standard assay for the quantification of NAbs providing availability of reagents.