Raffel J, Gafson A R, Malik O, Nicholas R
Department of Medicine, Imperial College London, UK
Department of Medicine, Imperial College London, UK.
Mult Scler. 2015 Dec;21(14):1833-8. doi: 10.1177/1352458515599681. Epub 2015 Oct 8.
Anti-JC virus antibody status is a risk factor for progressive multifocal leukoencephalopathy after natalizumab treatment in multiple sclerosis. Previous studies have used a cross-sectional approach to conclude that the presence and duration of natalizumab treatment does not influence anti-JCV Ab seropositivity.
Using a longitudinal approach, we measured change in anti-JCV Ab results after natalizumab treatment.
Anti-JCV Ab results (n = 1154) from the second-generation STRATIFY JCV™ DxSelect™ test were analysed from an observational cohort of MS patients on natalizumab (n = 485; n = 340 with repeat testing; n = 657 repeat tests on natalizumab).
Across sequential paired tests, seroconversion rate was greater than seroreversion rate (40/364 (11.0%) versus 18/293 (6.1%); p < 0.05). Moreover, anti-JCV Ab index increased across longitudinal paired tests (mA-B 0.102; paired t(656) = 5.0; p < 0.0001). This magnitude of Ab level increase far exceeds that expected due to increasing age alone.
Our data suggest that natalizumab therapy is associated with a significant and substantial increase in anti-JCV Ab index over time. Further work should focus on the underlying mechanisms of this phenomenon, and the clinical relevance to risk stratification.
抗JC病毒抗体状态是多发性硬化症患者接受那他珠单抗治疗后发生进行性多灶性白质脑病的一个危险因素。既往研究采用横断面研究方法得出结论,那他珠单抗治疗的存在与否及持续时间不影响抗JCV抗体血清阳性率。
我们采用纵向研究方法,测量那他珠单抗治疗后抗JCV抗体结果的变化。
对来自接受那他珠单抗治疗的MS患者观察队列的抗JCV抗体结果(n = 1154)进行分析,该队列中患者数量为485例;340例接受重复检测;657例接受那他珠单抗重复检测。
在连续配对检测中,血清转化发生率高于血清逆转发生率(40/364(11.0%)对18/293(6.1%);p < 0.05)。此外,在纵向配对检测中抗JCV抗体指数升高(mA - B 0.102;配对t(656) = 5.0;p < 0.0001)。这种抗体水平升高的幅度远远超过仅因年龄增长所预期的幅度。
我们的数据表明,随着时间推移,那他珠单抗治疗与抗JCV抗体指数显著大幅升高相关。进一步的研究应聚焦于这一现象的潜在机制以及与风险分层的临床相关性。