The importance of measuring IFNβ bioactivity:: Monitoring in MS patients and the effect of anti-IFNβ antibodies

Many multiple sclerosis (MS) patients treated with IFN beta develop anti-IFN beta antibodies, which can interfere with the bioactivity of the injected cytokine, i.e., antibody-mediated decreased bioactivity (ADB). The precise levels of anti-IFN beta antibodies inducing decreased bioactivity is unknown. We repeatedly used a bioactivity measure, gene expression of MxA or GEM, and correlated bioactivity with measures of binding and neutralizing antibodies. The binding antibody assay was a capture ELISA, and the neutralizing antibody (NAb) assay was a cytopathic effect (CPE) assay. 27% (17/64) of patients repeatedly sampled developed critical ADB. Bioactivity as determined by GEM correlated negatively with NAb titer, and bioactivity that had been lost with the development of NAbs returned if NAb levels diminished. These data reveal that the GEM assay is a useful adjunct in the management of MS patients treated with IFN beta, and that lost bioactivity returns when anti-IFN beta antibody levels diminish. (C) 2005 Elsevier B.V. All rights reserved.