Malucchi S, Gilli F, Caldano M, Marnetto F, Valentino P, Granieri L, Sala A, Capobianco M, Bertolotto A
Centro di Riferimento Regionale Sclerosi Multipla and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Regione Gonzole 10, I-10043 Orbassano, Torino, Italy.
Neurology. 2008 Mar 25;70(13 Pt 2):1119-27. doi: 10.1212/01.wnl.0000304040.29080.7b. Epub 2008 Feb 13.
Prolonged therapy with interferon beta (IFN beta) often leads to the development of anti-IFN beta binding antibodies (BAbs). A subset of the BAbs is of a neutralizing nature (neutralizing antibodies, NAbs) and is associated with reduced clinical efficacy of therapy. Myxovirus-resistance-protein A (MxA) has proven to be a reliable biomarker of IFN beta bioactivity. We analyzed the prognostic value of MxA mRNA, NAbs, and BAbs on the risk of having a new relapse in IFN beta-treated patients.
A 3-year study was conducted in 137 IFN beta-treated patients. Blood samples for BAbs, NAbs, and MxA mRNA measurements were taken after 12 +/- 3 months of therapy. Analysis of relapse-free survival (RFS) was performed for all measures by using known thresholds, generating "positive" and "negative" groups. Also, time between sampling and following relapse and risk of new relapses were calculated.
The MxA-negative group showed poorer RFS rates than the MxA-positive group [p < 0.0001, hazard ratio (HR) = 2.87]. Likewise, the NAb-positive group showed poorer RFS rates than the NAb-negative group (p =0.0013; HR = 2.49). On the contrary, BAb measurement did not show a clear clinical significance.
Findings indicate that measurements of both myxovirus-resistance-protein A (MxA) and neutralizing antibodies (NAbs) predict the risk of new relapses; however, the slightly stronger prognostic significance of MxA mRNA and the easier method for it measurement make MxA mRNA the preferred biomarker for monitoring interferon beta (IFN beta)-treated patients. This information can be used to better tailor treatment to the individual patient with MS.
长期使用β-干扰素（IFNβ）治疗常常会导致抗IFNβ结合抗体（BAb）的产生。一部分BAb具有中和性质（中和抗体，NAb），并与治疗的临床疗效降低相关。抗黏液病毒蛋白A（MxA）已被证明是IFNβ生物活性的可靠生物标志物。我们分析了MxA mRNA、NAb和BAb对IFNβ治疗患者再次复发风险的预后价值。
对137例接受IFNβ治疗的患者进行了为期3年的研究。在治疗12±3个月后采集血液样本用于检测BAb、NAb和MxA mRNA。通过使用已知阈值对所有指标进行无复发生存期（RFS）分析，分为“阳性”和“阴性”组。此外，还计算了采样至随后复发的时间以及再次复发的风险。
MxA阴性组的RFS率低于MxA阳性组[p < 0.0001，风险比（HR）= 2.87]。同样，NAb阳性组的RFS率低于NAb阴性组（p = 0.0013；HR = 2.49）。相反，BAb检测未显示出明确的临床意义。
研究结果表明，抗黏液病毒蛋白A（MxA）和中和抗体（NAb）的检测均可预测再次复发的风险；然而，MxA mRNA的预后意义稍强且检测方法更简便，使其成为监测β-干扰素（IFNβ）治疗患者的首选生物标志物。这些信息可用于更好地为多发性硬化症患者量身定制个体化治疗方案。
