Libertinova Jana, Meluzinova Eva, Matoska Vaclav, Zajac Miroslav, Kovarova Ivana, Havrdova Eva, Horakova Dana, Tomek Ales, Marusic Petr, Bojar Martin
Department of Neurology Charles University 2nd Faculty of Medicine and Motol University Hospital Prague Czech Republic.
Laboratory of Molecular Diagnostics Na Homolce Hospital Prague Czech Republic.
Brain Behav. 2017 Feb 9;7(3):e00644. doi: 10.1002/brb3.644. eCollection 2017 Mar.
Multiple sclerosis (MS) patients treated with interferon beta (IFNβ) are at risk of a declining response to treatment because of the production of IFNβ-neutralizing antibodies (NAbs). The expression of Myxovirus resistance protein A (MxA) mRNA is regarded as a marker of IFNβ bioactivity.
The aim of this study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its relationship to NAb production.
A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNβ treatment. NAbs and MxA mRNA were monitored every six months.
119 patients were consecutively enrolled and 107 were included in the final analysis. Both the presence of NAbs and a decrease in MxA mRNA below the cut off were revealed in 15 patients, however, in six patients (40%) positivity for NAbs was preceded by the decrease in MxA mRNA. In addition, a further six patients showing a decline in MxA mRNA did not have detectable NAbs.
Our data indicate that quantification of MxA mRNA is a more sensitive identifier of loss of IFNβ efficacy than the NAb positivity.
接受β-干扰素(IFNβ)治疗的多发性硬化症(MS)患者由于产生IFNβ中和抗体(NAbs)而面临治疗反应下降的风险。黏液病毒抗性蛋白A(MxA)mRNA的表达被视为IFNβ生物活性的标志物。
本研究的目的是分析长期IFNβ治疗期间MxA mRNA表达的动力学,并评估其与NAb产生的关系。
对开始IFNβ治疗的多发性硬化症患者设计了一项前瞻性、观察性、开放标签、非随机研究。每六个月监测一次NAbs和MxA mRNA。
连续纳入119例患者,107例纳入最终分析。15例患者同时出现NAbs阳性和MxA mRNA低于临界值的情况,然而,在6例患者(40%)中,NAbs阳性之前MxA mRNA就已下降。此外,另有6例MxA mRNA下降的患者未检测到NAbs。
我们的数据表明,与NAb阳性相比,MxA mRNA定量是IFNβ疗效丧失更敏感的指标。