van der Voort L F, Visser A, Knol D L, Oudejans C B M, Polman C H, Killestein J
Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Eur J Neurol. 2009 Sep;16(9):1049-52. doi: 10.1111/j.1468-1331.2009.02649.x. Epub 2009 May 22.
Treatment failure to Interferon-beta (IFNbeta) in multiple sclerosis (MS) can only partly be explained by anti-IFNbeta neutralising antibodies (NAb). Myxovirus resistance protein A (MxA) mRNA, reflecting IFNbeta bioactivity, is studied as an alternative biomarker for IFNbeta therapy response. Although absent IFNbeta bioactivity is associated with NAb and NAb are associated with reduced drug efficacy, the direct relationship between IFNbeta bioactivity and clinical disease activity is largely unknown.
We enrolled 126 consecutive relapsing-remitting MS patients on IFNbeta treatment. MxA mRNA expression was assessed 4 h after IFNbeta injection. Biological response status was determined after 3 months, by combined measurement of MxA mRNA expression and induction (MxA mRNA expression after/before IFNbeta injection). Patients were considered biological non-responders when both MxA mRNA expression and MxA mRNA induction were negative.
Biological non-responders showed a significantly higher annualised relapse rate and smaller proportion relapse-free patients compared with biological responders (relapse rate 0.81 vs. 0.37; proportion relapse free 37% vs. 67%).
Our results suggest that a lack of IFNbeta bioactivity is associated with the occurrence of relapses and therefore can be useful as a biomarker for unresponsiveness to IFNbeta.
在多发性硬化症（MS）中，干扰素-β（IFNβ）治疗失败仅部分可归因于抗IFNβ中和抗体（NAb）。反映IFNβ生物活性的Mx1抗病毒蛋白（MxA）mRNA作为IFNβ治疗反应的替代生物标志物进行研究。虽然缺乏IFNβ生物活性与NAb相关，且NAb与药物疗效降低相关，但IFNβ生物活性与临床疾病活动之间的直接关系很大程度上未知。
我们纳入了126例接受IFNβ治疗的复发缓解型MS患者。在注射IFNβ后4小时评估MxA mRNA表达。3个月后，通过联合测量MxA mRNA表达和诱导情况（注射IFNβ后/前的MxA mRNA表达）来确定生物学反应状态。当MxA mRNA表达和MxA mRNA诱导均为阴性时，患者被视为生物学无反应者。
与生物学反应者相比，生物学无反应者的年化复发率显著更高，无复发患者比例更小（复发率0.81对0.37；无复发比例37%对67%）。
我们的结果表明，缺乏IFNβ生物活性与复发的发生相关，因此可作为对IFNβ无反应的生物标志物。
