Key result
Interferon-beta induced IFI27, CCL2, and CXCL10 in MS patients, but this induction was reduced with low neutralizing antibody levels and lost with moderate/high levels.
Why the study?
Does interferon-beta administration induce specific gene expression markers (IFI27, CCL2, CXCL10) in multiple sclerosis patients, and is this induction affected by neutralizing antibodies?
Observational
Does interferon-beta administration induce specific gene expression markers (IFI27, CCL2, CXCL10) in multiple sclerosis patients, and is this induction affected by neutralizing antibodies?
IFI27, CCL2, and CXCL10 are sensitive biomarkers for the biological response to interferon-beta in multiple sclerosis, reflecting reduced bioactivity in the presence of neutralizing antibodies.
Supports IFI27, CCL2, CXCL10 as interferon-beta response biomarkers in MS; leaves open clinical utility pending prospective validation.
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.
No takes yet. Share an insight, caveat, or question.
Sellebjerg et al. (2009) conducted an observational in Multiple sclerosis. Interferon-beta vs. Untreated patients and NAb negative patients was evaluated on Gene expression induction (MxA, CXCL10, CCL2, IFI27). Interferon-beta induced IFI27, CCL2, and CXCL10 in MS patients, but this induction was reduced with low neutralizing antibody levels and lost with moderate/high levels.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: