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干扰素β治疗的多发性硬化症患者中抗黏液病毒蛋白A mRNA的表达动力学

Myxovirus Resistance Protein A mRNA Expression Kinetics in Multiple Sclerosis Patients Treated with IFNβ.

作者信息

Libertinova Jana, Meluzinova Eva, Tomek Ales, Horakova Dana, Kovarova Ivana, Matoska Vaclav, Kumstyrova Simona, Zajac Miroslav, Hyncicova Eva, Liskova Petra, Houzvickova Eva, Martinkovic Lukas, Bojar Martin, Havrdova Eva, Marusic Petr

机构信息

Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.

Department of Neurology and Center of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.

出版信息

PLoS One. 2017 Jan 12;12(1):e0169957. doi: 10.1371/journal.pone.0169957. eCollection 2017.

Abstract

INTRODUCTION

Interferon-β (IFNß) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is a marker of IFNß bioactivity, which may be reduced by neutralizing antibodies (NAbs) against IFNß. The aim of the study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its predictive value.

METHODS

A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNß treatment. MxA mRNA was assessed prior to initiation of IFNß therapy and every three months subsequently. NAbs were assessed every six months. Assessment of relapses was scheduled every three months during 24 months of follow up. The disease activity was correlated to the pretreatment baseline MxA mRNA value. In NAb negative patients, clinical status was correlated to MxA mRNA values.

RESULTS

119 patients were consecutively enrolled and 107 were included in the final analysis. There was no correlation of MxA mRNA expression levels between baseline and month three. Using survival analysis, none of the selected baseline MxA mRNA cut off points allowed prediction of time to first relapse on the treatment. In NAb negative patients, mean MxA mRNA levels did not significantly differ in patients irrespective of relapse status.

CONCLUSION

Baseline MxA mRNA does not predict the response to IFNß treatment or the clinical status of the disease and the level of MxA mRNA does not correlate with disease activity in NAb negative patients.

摘要

引言

干扰素-β(IFNβ)是复发缓解型多发性硬化症的一线治疗药物。Mx1蛋白(MxA)是IFNβ生物活性的标志物,针对IFNβ的中和抗体(NAbs)可能会使其降低。本研究的目的是分析长期IFNβ治疗期间MxA mRNA表达的动力学,并评估其预测价值。

方法

设计了一项针对开始IFNβ治疗的多发性硬化症患者的前瞻性、观察性、开放标签、非随机研究。在开始IFNβ治疗前及随后每三个月评估一次MxA mRNA。每六个月评估一次NAbs。在24个月的随访期间,每三个月安排一次复发评估。将疾病活动与治疗前基线MxA mRNA值相关联。在NAb阴性患者中,将临床状态与MxA mRNA值相关联。

结果

连续纳入119例患者,最终分析纳入107例。基线与第三个月之间的MxA mRNA表达水平无相关性。使用生存分析,所选的基线MxA mRNA截断点均无法预测治疗后首次复发的时间。在NAb阴性患者中,无论复发状态如何,患者的平均MxA mRNA水平均无显著差异。

结论

基线MxA mRNA不能预测对IFNβ治疗的反应或疾病的临床状态,并且在NAb阴性患者中,MxA mRNA水平与疾病活动无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35d8/5231341/9c6f5897fc11/pone.0169957.g001.jpg

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