OBJECTIVE: Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)-beta. NAbs impair the effect of treatment. The biological effect of IFN-beta can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other markers could be more sensitive for evaluating the response to IFN-beta. We used DNA array analysis to identify genes that are strongly induced in blood cells by IFN-beta, and measured their expression in MS patients with different NAb levels. METHODS: Gene expression was studied on DNA arrays in untreated patients, in NAb negative patients, and in MS patients with varying NAb levels 9-12 h and 36-48 h after IFN-beta administration. The expression of selected genes was measured by real-time PCR. NAb levels were assessed by a cytopathic effect assay. RESULTS: Several hundred genes were induced 9-12 h after an injection of IFN-beta. The molecules CXCL10, CCL2 and IFI27 were among the most strongly induced. Gene induction was generally much less pronounced after 36-48 h, but IFI27 remained strongly induced. The strong induction of these molecules and MxA was confirmed by real-time PCR. Induction of MxA, CCL2, CXCL10 and IFI27 was reduced in patients with low NAb levels and lost in patients with intermediate/high NAb levels. CONCLUSION: We identify IFI27, CCL2 and CXCL10 as sensitive biomarkers for the response to IFN-beta. The expression of these markers adequately reflects bioactivity of IFN-ss as documented by the decreased induction in low NAb-positive patients and the lost induction in patients with moderate/high NAb levels
Udgivelsesdato: 2009/12