Antoniol Caroline, Stankoff Bruno
AP-HP, Hôpital Saint-Antoine , Paris , France ; Centre Hospitalier Universitaire de Dijon, Université de Bourgogne , Dijon , France.
AP-HP, Hôpital Saint-Antoine , Paris , France ; Sorbonne Universités, Université Pierre et Marie Curie, UMR S 1127, CNRS UMR 7225, and l'Institut du Cerveau et de la Moelle Épinière (ICM) , Paris , France.
Front Immunol. 2015 Jan 5;5:668. doi: 10.3389/fimmu.2014.00668. eCollection 2014.
Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain, has been approved for the treatment of active multiple sclerosis, but expose to the onset of a rare side effect, progressive multifocal leukoencephalopathy (PML). Estimating the individual risk of PML in NTZ-treated patients is a major challenge, and therapeutic strategies are mainly guided by the overall PML risk assessed by identified risk factors: JC virus (JCV) seropositivity, treatment duration (with peak incidence after 24 months), and the previous use of immunosuppressive therapies. Given that this stratification does not yet allow a precise individual prediction of PML, other predictive markers are needed, and several immunological biomarkers have been described. Quantification of anti-JCV antibody levels may improve individual predictive value, with higher baseline titers indicating increased risk. Other immunological biomarkers such as leukocyte cell membrane markers (CD49d, CD11a, and CD62L), detection of circulating JCV-specific activated T effector memory cells (TEM) or genetic screening have been proposed. In this review, we discuss how recent progress in immunology has paved the way for «new combined monitoring», which will include immunological screening, in NTZ-treated patients.
那他珠单抗（NTZ）是一种识别α4整合素链的单克隆抗体，已被批准用于治疗活动性多发性硬化症，但会引发一种罕见的副作用——进行性多灶性白质脑病（PML）。评估接受NTZ治疗的患者发生PML的个体风险是一项重大挑战，治疗策略主要依据已确定的风险因素评估的总体PML风险来指导：JC病毒（JCV）血清学阳性、治疗持续时间（24个月后发病率达到峰值）以及既往使用免疫抑制疗法的情况。鉴于这种分层尚无法精确预测个体发生PML的情况，因此需要其他预测标志物，并且已经描述了几种免疫生物标志物。抗JCV抗体水平的量化可能会提高个体预测价值，基线滴度越高表明风险增加。还提出了其他免疫生物标志物，如白细胞细胞膜标志物（CD49d、CD11a和CD62L）、检测循环中的JCV特异性活化效应记忆T细胞（TEM）或进行基因筛查。在本综述中，我们讨论了免疫学的最新进展如何为NTZ治疗患者的“新型联合监测”铺平道路，这种监测将包括免疫筛查。
