Verheyen Jens, Maizus Kseniya, Feist Eugen, Tolman Zebulon, Knops Elena, Saech Jasemine, Spengler Lydia, Waterboer Tim, Burmester Gerd R, Pawlita Michael, Pfister Herbert, Rubbert-Roth Andrea
Institute of Virology, National Reference Center for Papilloma- and Polyomaviruses, University of Cologne, Cologne, Germany,
Med Microbiol Immunol. 2015 Oct;204(5):613-8. doi: 10.1007/s00430-015-0390-5. Epub 2015 Feb 13.
Progressive multifocal leukoencephalopathy (PML) represents a rare but potentially fatal reactivation of JC-polyomavirus (JCPyV) recently also reported in patients with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA) treated with rituximab. The aim of the present study was to analyse the pattern of JCPyV infections in patients with RA undergoing treatment with biologic agents. Urine and blood samples were analysed from 80 patients for antibody levels and/or the presence of JCPyV DNA. Genotyping of the control region and VP1 was performed for all JCPyV DNA-positive specimens. Viremia of JCPyV was only temporarily detected in two patients, and these viruses did not carry any mutations associated with the occurrence of PML. JCPyV DNA was prevalent in initial urine samples of 33% of all patients. RA patients who have consecutively been treated with two or more biologic agents revealed significantly higher prevalence of JCPyV DNA in the urine compared to RA patients treated with their first biologic agent. The presence of JCPyV DNA in the urine closely correlated to JCPyV antibody positivity, and therefore, antibody titres were higher in RA patients who had consecutively received two or more biologic agents over time. Therefore, the overall number of biologic agents had an impact on the pattern of JCPyV detection in this study. Hence, JCPyV antibody screening might be useful as part of the PML risk stratification for RA patients in the future.
进行性多灶性白质脑病（PML）是一种罕见但可能致命的JC多瘤病毒（JCPyV）再激活疾病，最近在接受利妥昔单抗治疗的自身免疫性疾病患者（如系统性红斑狼疮和类风湿关节炎（RA））中也有报道。本研究的目的是分析接受生物制剂治疗的RA患者中JCPyV感染的模式。对80例患者的尿液和血液样本进行了抗体水平和/或JCPyV DNA存在情况的分析。对所有JCPyV DNA阳性标本进行了控制区和VP1基因分型。仅在两名患者中暂时检测到JCPyV病毒血症，并且这些病毒未携带任何与PML发生相关的突变。JCPyV DNA在所有患者初始尿液样本中的阳性率为33%。与接受第一种生物制剂治疗的RA患者相比，连续接受两种或更多种生物制剂治疗的RA患者尿液中JCPyV DNA的阳性率显著更高。尿液中JCPyV DNA的存在与JCPyV抗体阳性密切相关，因此，随着时间的推移，连续接受两种或更多种生物制剂治疗的RA患者的抗体滴度更高。因此，在本研究中，生物制剂的总体数量对JCPyV检测模式有影响。因此，JCPyV抗体筛查未来可能作为RA患者PML风险分层的一部分而有用。
