scholarly journals JC Virus-DNA Detection Is Associated with CD8 Effector Accumulation in Peripheral Blood of Patients with Multiple Sclerosis under Natalizumab Treatment, Independently from JC Virus Serostatus

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Maria A. Zingaropoli ◽  
Marco Iannetta ◽  
Simona Pontecorvo ◽  
Elena Anzivino ◽  
Carla Prezioso ◽  
...  

Although natalizumab (anti-α4 integrin) represents an effective therapy for relapsing remitting multiple sclerosis (RRMS), it is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 (N0), 1–12 (N12), 13–24 (N24), 25–36 (N36), and over 36 (N>36) infusions. JCV-DNA was detected in plasma and urine. T-lymphocyte phenotype was evaluated with flow cytometry. JCV serostatus was assessed. Ten healthy donors (HD), whose ages and sexes matched with the RRMS patients of theN0 group, were enrolled. CD8 effector (CD8 E) percentages were increased in natalizumab treated patients with detectable JCV-DNA in plasma or urine compared to JCV-DNA negative patients (JCV−) (p<0.01andp<0.001, resp.). Patients with CD8 E percentages above 10.4% tended to show detectable JCV-DNA in plasma and/or urine (ROC curvep=0.001). The CD8 E was increased when JCV-DNA was detectable in plasma or urine, independently from JCV serology, forN12 andN24 groups (p<0.01). As long as PML can affect RRMS patients under natalizumab treatment with a negative JCV serology, the assessment of CD8 E could help in the evaluation of JCV reactivation.

2012 ◽  
Vol 14 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Colleen E. Miller ◽  
Mary Karpinski ◽  
Mary Ann Jezewski

This phenomenological investigation was undertaken to gain a better understanding of multiple sclerosis (MS) patients' experience with natalizumab (Tysabri; Biogen Idec Inc, Cambridge, MA) treatment and its impact on their quality of life (QOL). Twenty MS patients who were receiving natalizumab treatment were recruited by the physicians, nurse practitioners, nurses, and social worker of the William C. Baird Multiple Sclerosis Center in Buffalo, New York, between March 2009 and November 2009. Patients were invited to participate if they had relapsing-remitting MS, had received at least six treatments of natalizumab, and could articulate their experience. An interviewer obtained informed consent, gathered basic demographic information, and then tape-recorded the participants' accounts of their experience with natalizumab. The audio-recorded interviews were transcribed and de-identified before being submitted to the investigators for analysis. The Atlas.ti qualitative data analysis program (Scolari, Berlin, Germany) was used to manage the data. Patients found natalizumab easy to tolerate and effective; moreover, they described improvement in their QOL. Patients must weigh the benefits of control of their MS against the increased risk of developing progressive multifocal leukoencephalopathy with natalizumab treatment. Information from this study will be used to educate professionals involved in MS patient care as well as patients and families considering treatment with natalizumab.


2020 ◽  
Vol 83 (5) ◽  
pp. 487-492
Author(s):  
Katarzyna Kapica-Topczewska ◽  
Francois Collin ◽  
Joanna Tarasiuk ◽  
Agata Czarnowska ◽  
Monika Chorąży ◽  
...  

<b><i>Introduction:</i></b> Presence of anti-JC-virus antibodies (JCVAbs) is associated with the increased risk of natalizumab (NAT)-related progressive multifocal leukoencephalopathy (PML). Little is known about seroconversion rate and time to seroconversion in relapsing-remitting multiple sclerosis (RRMS) patients treated with NAT in Poland. The aim of the study was to assess the true risk of PML, seroconversion rate, and time to seroconversion in all JCVAb-negative RRMS patients treated with NAT in Poland. <b><i>Methods:</i></b> Demographic and clinical data of all Polish RRMS patients treated with NAT reimbursed by National Health Fund (NFZ) were prospectively collected in electronic files using the Therapeutic Programme Monitoring System provided by NFZ. The assessment of JCVAb presence (without collection of JCVAb index value) in serum (Unilabs, STRATIFY JCV: anti-JCV antibody ELISA) was done at the beginning of therapy and then repeated every 6 months. The maximum follow-up time was 4 years. In Poland, since 2013, according to the NFZ drug program guidance, only patients with negative JCVAb test have started treatment with NAT. <b><i>Results:</i></b> In all Polish multiple sclerosis centers, 210 negative JCVAb RRMS patients with at least 9 (±3) months of observation (146 females, 64 males, and the median age at baseline: 33 years) were included in the study. During the follow-up period, JCVAb status changed from negative to positive in 34 patients (16.2%). For half of the patients, the seroconversion was diagnosed 1 year after starting NAT treatment. In 4 patients (1.9%) during follow-up, JCVAb status changed again from positive to negative. In Poland, before establishment of NFZ drug program, 4 cases of PML in patients treated with NAT in clinical trials were diagnosed. In the NFZ drug program, since 2013, no patient treated with NAT has been diagnosed with PML. <b><i>Conclusions:</i></b> NAT therapy in JCV-seronegative RRMS patients is safe and results in the absence of PML cases. In Poland, JCV seroconversion rate is similar to that observed in other European countries.


2017 ◽  
Vol 24 (11) ◽  
pp. 1453-1460 ◽  
Author(s):  
Cyra E Leurs ◽  
Zoé LE van Kempen ◽  
Iris Dekker ◽  
Lisanne J Balk ◽  
Mike P Wattjes ◽  
...  

Background: Natalizumab is an effective treatment in relapsing-remitting multiple sclerosis (MS). Mainly because of the risk of progressive multifocal leukoencephalopathy (PML), a substantial proportion of John Cunningham (JC) virus–positive patients switch to fingolimod. Previous reports show a clear benefit when the duration of a washout (WO) period of natalizumab is 0–3 months in comparison to longer WO periods. However, there is no consensus regarding the optimal duration of a WO period under 3 months. Objective: We compared MS disease activity after different WO periods. In addition, we investigated several factors that possibly influence recurrence of disease activity, including serum natalizumab concentration and lymphocyte counts. Methods: From a prospective observational cohort study of natalizumab-treated patients, we selected 52 patients who switched to fingolimod. We divided the patients in three groups (<6 weeks, 6–8 weeks, >8 weeks WO). Serum natalizumab concentration and lymphocyte count were assessed during and after natalizumab treatment. Results: Patients with a WO period of >8 weeks had a significant higher recurrence of disease activity (odds ratio, 6.8; 95% confidence interval, 1.4–32.8) compared to patients with a WO period of <6 weeks. Serum natalizumab concentration and lymphocyte count did not predict recurrence of disease activity. Interpretation: A short WO period decreases the risk of recurrence of disease activity. The possible impact of a short WO period on the risk of carry-over PML in JC virus–positive patients remains uncertain.


2018 ◽  
Vol 41 (6) ◽  
pp. 199-201 ◽  
Author(s):  
Hussein Algahtani ◽  
Bader Shirah ◽  
Hind Abobaker ◽  
Nebras Alghanaim ◽  
Fatemah Kamel

2010 ◽  
Vol 17 (2) ◽  
pp. 198-203 ◽  
Author(s):  
Sven G Meuth ◽  
Stefan Bittner ◽  
Carola Seiler ◽  
Kerstin Göbel ◽  
Heinz Wiendl

Background and Objective: The objective of this study was to examine the effects of natalizumab on functional parameters assessed by evoked potentials (visual [VEP], somatosensory [SEP] and motor evoked potentials [MEP]) in a cohort study in relapsing–remitting multiple sclerosis patients. Methods: EP data of 44 patients examined 12 months prior to natalizumab treatment, at the timepoint of treatment initiation and 1 year later were compared. Sum scores (VEP, MEP, SEP) were evaluated and correlated with the Expanded Disability Status Scale. Results: Improvement of the VEP sum score was found in 33% of natalizumab-treated patients but only in 9% of the same patients prior to treatment ( p = 0.041). A comparable situation was found for SEP (improvement: 32% versus 5%; worsening: 11% versus 37%; p = 0.027). For MEP no significant differences were seen (improvement: 10% versus 18%; worsening: 5% versus 29%; p = 0.60). EP recordings (VEP = SEP > MEP) have the capacity to demonstrate treatment effects of natalizumab on a functional level. Conclusions: Natalizumab therapy increases the percentage of patients showing stable or even ameliorated electrophysiological parameters in the investigated functional systems.


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