Sorensen P S, Koch-Henriksen N, Bendtzen K
Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Mult Scler. 2007 Jun;13(5):616-21. doi: 10.1177/1352458506072344. Epub 2007 Feb 9.
Neutralising antibodies (NAbs) against interferon (IFN)-beta reduce the treatment effect in multiple sclerosis (MS). However, data from pivotal trials of IFN-beta in MS suggest that NAb-positive patients may have a reduced relapse rate during the first six to 12 months of therapy. We collected clinical data and plasma samples for NAb measurements prospectively, every six months, in 468 patients treated with the same IFN-beta preparation for at least 24 months. NAbs were measured blindly with a cytopathic effect (CPE) assay. During treatment months 0-6, patients who became NAb-positive had significantly fewer relapses compared to patients who maintained the NAb-negative status, whereas the opposite was observed after month 6. This is in accordance with observations in randomised studies of the three different IFN-beta preparations, showing that patients who become NAb-positive have lower relapse rates during the first six or 12 months of therapy. We hypothesise that low affinity NAbs, present early after the start of IFN-beta therapy, though neutralising in vitro in sensitive assays increase the half-life of IFN-beta in vivo and, thereby, enhance the therapeutic effect. With affinity maturation, NAbs effectively prevent IFN-beta binding to its receptors also in vivo and, hence, abolish the treatment effect.
抗干扰素（IFN）-β的中和抗体（NAbs）会降低多发性硬化症（MS）的治疗效果。然而，IFN-β治疗MS的关键试验数据表明，NAb阳性患者在治疗的前6至12个月内复发率可能会降低。我们前瞻性地每六个月收集468例接受相同IFN-β制剂治疗至少24个月患者的临床数据和血浆样本用于NAb检测。采用细胞病变效应（CPE）试验对NAbs进行盲法检测。在治疗的0至6个月期间，与维持NAb阴性状态的患者相比，NAb转为阳性的患者复发明显较少，而在6个月后观察到相反的情况。这与三种不同IFN-β制剂的随机研究结果一致，表明在治疗的前6或12个月内，NAb转为阳性的患者复发率较低。我们推测，IFN-β治疗开始后早期出现的低亲和力NAbs，尽管在敏感试验中体外具有中和作用，但会增加IFN-β在体内的半衰期，从而增强治疗效果。随着亲和力成熟，NAbs在体内也能有效阻止IFN-β与其受体结合，因此会消除治疗效果。
