Dominguez-Mozo Maria Inmaculada, Garcia-Montojo Marta, De Las Heras Virginia, Garcia-Martinez Angel, Arias-Leal Ana María, Casanova Ignacio, Arroyo Rafael, Alvarez-Lafuente Roberto
Unidad de Esclerosis Múltiple, Hospital Clínico San Carlos. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain,
J Neuroimmune Pharmacol. 2013 Dec;8(5):1277-86. doi: 10.1007/s11481-013-9496-y. Epub 2013 Aug 25.
One of the most effective multiple sclerosis (MS) treatment is natalizumab. Nevertheless, it has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML) caused by the JC virus (JCV). Our main objective was to assess the utility of testing JCV-DNA, apart from anti-JCV antibodies, to determine which natalizumab-treated MS patients has been previously in contact with the virus. For this purpose, 138 MS natalizumab/non-natalizumab treated patients participated in several studies. Cross-sectional study (CS): association of several epidemiological variables with anti-JCV antibodies and JCV-DNA levels in PBMC/serum/urine. First longitudinal study (A): evaluation of JCV-DNA prevalence in urine throughout the treatment. Second longitudinal study (B): simultaneous assessment of antibodies and viral DNA levels in PBMC/serum/urine at two time points. CS: The seropositivity rate for anti-JCV antibodies (62.3 %) and JCV prevalence in urine (59.4 %) were similar; although 26 % of our population was positive only using one of the two techniques. A: The viral prevalence in urine seemed to increase between the baseline visit and the others (Baseline-Visit/V18months, p = 0.006). B: Our rate of positive antibody seroconversion was 36 %. Nearly all patients with detectable JCV-DNA levels in PBMC excreted the virus intermittently in urine; while our PML case, positive in PBMC and serum samples 2 month before the PML, excreted JCV permanently. In conclusion, the determination of JCV DNA levels in urine could be complementary to anti-JCV antibodies for identifying MS patients who has been infected by the JCV. Further research would be necessary to understand the different JCV excretion profiles in urine.
那他珠单抗是治疗多发性硬化症（MS）最有效的药物之一。然而，它与由JC病毒（JCV）引起的进行性多灶性白质脑病（PML）风险增加有关。我们的主要目标是评估检测JCV-DNA（除抗JCV抗体外）的效用，以确定哪些接受那他珠单抗治疗的MS患者先前已接触过该病毒。为此，138例接受那他珠单抗/未接受那他珠单抗治疗的MS患者参与了多项研究。横断面研究（CS）：若干流行病学变量与外周血单核细胞/血清/尿液中抗JCV抗体和JCV-DNA水平的关联。首次纵向研究（A）：评估整个治疗过程中尿液中JCV-DNA的流行情况。第二次纵向研究（B）：在两个时间点同时评估外周血单核细胞/血清/尿液中的抗体和病毒DNA水平。CS：抗JCV抗体的血清阳性率（62.3%）和尿液中JCV的流行率（59.4%）相似；尽管我们的研究人群中有26%仅使用两种技术之一呈阳性。A：尿液中的病毒流行率在基线访视和其他访视之间似乎有所增加（基线访视/18个月访视，p = 0.006）。B：我们的抗体血清阳转率为36%。几乎所有外周血单核细胞中可检测到JCV-DNA水平的患者在尿液中间歇性排出病毒；而我们的PML病例在PML前2个月外周血单核细胞和血清样本呈阳性，持续排出JCV。总之，检测尿液中的JCV DNA水平对于识别已感染JCV的MS患者可能是抗JCV抗体的补充。有必要进行进一步研究以了解尿液中不同的JCV排泄情况。
