Interferon-beta-1b-induced short- and long-term signatures of treatment activity in multiple sclerosis.
Interferon-beta-1b-induced short- and long-term signatures of treatment activity in multiple sclerosis.
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DOI：
10.1038/tpj.2012.27
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Salamon H
中科院分区：
文献类型：
--
作者：
Croze E;Yamaguchi KD;Knappertz V;Reder AT;Salamon H
干扰素β可减轻复发缓解型多发性硬化症患者的疾病负担。本研究结合干扰素β-1b治疗多发性硬化症患者的基因表达谱和生物学基础，研究干扰素β的多效性作用机制。发现了与免疫调节、线粒体脂肪酸代谢和抗氧化活性有关的基因。神经元保护的可能中介包括NRF2，抗氧化抑制因子OLA1的下调，以及与视神经病变和MS样病变有关的抗氧化基因ND6。网络分析强调了IKBKE，它可能在病毒反应和能量代谢中发挥作用。对治疗初期多发性硬化症和干扰素β相关基因表达的比较分析表明，多发性硬化症患者存在干扰素β不足。我们观察到长期治疗中比急性给药期间更多的基因表达变化。这些不同的短期和长期影响是由不同的转录因子驱动的。干扰素β治疗效果的多基因生物标志物特征被开发出来，随后在独立的干扰素β-1b治疗的多发性硬化症研究中得到证实，但在格列替拉默治疗的患者中没有得到证实。
Interferon beta (IFNβ) reduces disease burden in relapsing-remitting multiple sclerosis (MS) patients. In this study, IFNβ-1b-treated MS patient gene expression profiles and biological knowledgebases were integrated to study IFNβ's pleiotropic mechanisms of action. Genes involved in immune regulation, mitochondrial fatty acid metabolism and antioxidant activity were discovered. Plausible mediators of neuronal preservation included NRF2, downregulation of OLA1, an antioxidant suppressor, and the antioxidant gene ND6, implicated in optic neuropathy and MS-like lesions. Network analysis highlighted IKBKE, which likely has a role in both viral response and energy metabolism. A comparative analysis of therapy-naive MS- and IFNβ-associated gene expression suggests an IFNβ insufficiency in MS. We observed more gene expression changes in long-term treatment than during acute dosing. These distinct short- and long-term effects were driven by different transcription factors. Multi-gene biomarker signatures of IFNβ treatment effects were developed and subsequently confirmed in independent IFNβ-1b-treated MS studies, but not in glatiramer acetate-treated patients.
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影响因子：
5
作者：
Esposito, F.;Patsopoulos, N. A.;Cepok, S.;Kockum, I.;Leppa, V.;Booth, D. R.;Heard, R. N.;Stewart, G. J.;Cox, M.;Scott, R. J.;Lechner-Scott, J.;Goris, A.;Dobosi, R.;Dubois, B.;Rioux, J. D.;Oturai, A. B.;Sondergaard, H. B.;Sellebjerg, F.;Sorensen, P. S.;Reunanen, M.;Koivisto, K.;Cournu-Rebeix, I.;Fontaine, B.;Winkelmann, J.;Gieger, C.;Infante-Duarte, C.;Zipp, F.;Bergamaschi, L.;Leone, M.;Bergamaschi, R.;Cavalla, P.;Lorentzen, A. R.;Mero, I-L;Celius, E. G.;Harbo, H. F.;Spurkland, A.;Comabella, M.;Brynedal, B.;Alfredsson, L.;Bernardinelli, L.;Robertson, N. P.;Hawkins, C. P.;Barcellos, L. F.;Beecham, G.;Bush, W.;Cree, B. A. C.;Daly, M. J.;Ivinson, A. J.;Aubin, C.;Compston, A.;D'Alfonso, S.;Haines, J. L.;Hauser, S. L.;Hemmer, B.;Hillert, J.;McCauley, J. L.;Oksenberg, J.;Olsson, T.;Palotie, A.;Peltonen, L.;Pericak-Vance, M. A.;Saarela, J.;Sawcer, S. J.;Stranger, B.;Boneschi, F. M.;Comi, G.;Hafler, D. A.;de Bakker, P. I. W.;De Jager, P. L.
通讯作者：
De Jager, P. L.
影响因子：
14.5
作者：
Comabella, M.;Luenemann, J. D.;Martin, R.
通讯作者：
Martin, R.
影响因子：
27.4
作者：
Corr M;Boyle DL;Ronacher L;Flores N;Firestein GS
通讯作者：
Firestein GS
影响因子：
14.5
作者：
Kovács, GG;Höftberger, R;Jakab, G
通讯作者：
Jakab, G
影响因子：
2.1
作者：
Goertsches, Robert H.;Hecker, Michael;Zettl, Uwe K.
通讯作者：
Zettl, Uwe K.