JC virus antibody index in natalizumab-treated patients: correlations with John Cunningham virus DNA and C-reactive protein level

Abstract

Roberta Lanzillo,1 Raffaele Liuzzi,2 Luca Vallefuoco,3 Marcello Moccia,1 Luca Amato,1 Giovanni Vacca,1 Veria Vacchiano,1 Giuseppe Portella,3 Vincenzo Brescia Morra1 1Neurological Sciences Department, Federico II University, 2Institute of Biostructure and Bioimaging, National Research Council, 3Clinical Pathology Department, Federico II University, Naples, ItalyAbstract: Natalizumab-treated patients have a higher risk of developing progressive multifocal leukoencephalopathy. Exposure to John Cunningham virus (JCV) is a prerequisite for PML (progressive multifocal leukoencephalopathy). To assess JCV exposure in multiple sclerosis patients, we performed a serological examination, obtained the antibody index, performed real-time polymerase chain reaction (PCR) to detect JCV DNA in plasma and urine, and investigated the role of ultrasensitive C-reactive protein (usCRP) as a possible biological marker of JCV reactivation. We retrospectively analyzed consecutive natalizumab-treated multiple sclerosis patients who underwent a JCV antibody test through a two-step enzyme-linked immunosorbent assay (STRATIFY test) to the measure of serum usCRP levels, and to perform blood and urine JCV PCR. The studied cohort included 97 relapsing–remitting patients (60 women). Fifty-two patients (53.6%) tested positive for anti-JCV antibodies. PCR showed JCV DNA in the urine of 30 out of 83 (36.1%) patients and 28 out of 44 seropositive patients (63.6%), with a 6.7% false-negative rate for the STRATIFY test. Normalized optical density values were higher in urinary JCV DNA-positive patients (P<0.0001). Interestingly, the level of usCRP was higher in urinary JCV DNA-positive patients and correlated to the number of DNA copies in urine (P=0.028). As expected, patients' age correlated with JCV seropositivity and with JC viruria (P=0.02 and P=0.001, respectively). JC viruria was significantly correlated with a high JCV antibody index and high serum usCRP levels. We suggest that PCR and usCRP might be useful as markers of JCV reactivation, and that patients should be monitored between STRATIFY assessments.Keywords: multiple sclerosis, John Cunningham virus, natalizumab, antibodies, polymerase chain reaction, ultrasensitive C-reactive protein