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.
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 MSpatients with different NAb levels. METHODS: Gene expression was studied on DNA arrays in untreated patients, in NAb negative patients, and in MSpatients 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.
Authors: Antonio Bertolotto; Marco Capobianco; Maria Pia Amato; Elisabetta Capello; Ruggero Capra; Diego Centonze; Maria Di Ioia; Antonio Gallo; Luigi Grimaldi; Luisa Imberti; Alessandra Lugaresi; Chiara Mancinelli; Maria Giovanna Marrosu; Lucia Moiola; Enrico Montanari; Silvia Romano; Luigina Musu; Damiano Paolicelli; Francesco Patti; Carlo Pozzilli; Silvia Rossi; Marco Salvetti; Gioachino Tedeschi; Maria Rosaria Tola; Maria Trojano; Maria Troiano; Mauro Zaffaroni; Simona Malucchi Journal: Neurol Sci Date: 2013-12-29 Impact factor: 3.307
Authors: Finn Sellebjerg; Martin Krakauer; Signe Limborg; Dan Hesse; Henrik Lund; Annika Langkilde; Helle Bach Søndergaard; Per Soelberg Sørensen Journal: PLoS One Date: 2012-06-06 Impact factor: 3.240
Authors: Alexander Hundeshagen; Michael Hecker; Brigitte Katrin Paap; Charlotte Angerstein; Ole Kandulski; Christian Fatum; Christiane Hartmann; Dirk Koczan; Hans-Juergen Thiesen; Uwe Klaus Zettl Journal: J Neuroinflammation Date: 2012-06-22 Impact factor: 8.322
Authors: Richard A Rudick; M R Sandhya Rani; Yaomin Xu; Jar-Chi Lee; Jie Na; Jennifer Shrock; Anupama Josyula; Elizabeth Fisher; Richard M Ransohoff Journal: PLoS One Date: 2011-05-13 Impact factor: 3.240
Authors: Sunny Malhotra; Marta F Bustamante; Francisco Pérez-Miralles; Jordi Rio; Mari Carmen Ruiz de Villa; Esteban Vegas; Lara Nonell; Florian Deisenhammer; Nicolás Fissolo; Ramil N Nurtdinov; Xavier Montalban; Manuel Comabella Journal: PLoS One Date: 2011-08-23 Impact factor: 3.240