Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study

Hegen, Harald; Auer, Michael; Bsteh, Gabriel; Pauli, Franziska Di; Plavina, Tatiana; Walde, Janette; Deisenhammer, Florian; Berger, Thomas

doi:10.1371/journal.pone.0174005

Cited by 28 publications

(37 citation statements)

References 22 publications

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“…We suggest that FTY should be used with caution in patients with JCV‐seropositive or high anti‐JCV antibody index (>1.5) 72, 73. Patients who develop new neurological symptoms suggestive of PML should be urgently evaluated at very early stage and have expeditious MRI and JCV‐polymerase chain reaction analysis.…”

Section: Fingolimod and Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

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Fingolimod (FTY) is the first oral medication approved for treatment of relapsing–remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long‐term post‐marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side‐effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of FTY; (ii) safety profile; (iii) post‐marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after FTY withdrawal; (vi) relationship between FTY and progressive multifocal leukoencephalopathy; (vii) FTY and progressive multifocal leukoencephalopathy‐related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.

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Section: Fingolimod and Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

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“…Regardless of DMD, most subjects showed stable anti‐JCV antibody status over time. We did not find any sign of a higher seroconversion rate in Natalizumab‐treated patients as it was described in previous studies (Hegen et al, ; Schwab et al, ; Vennegoor et al, ; Warnke et al, ), with the limitation that our study was not powered for treatment questions. We observed different anti‐JCV antibody prevalence at baseline between the Natalizumab and Fingolimod group.…”

Section: Discussionmentioning

confidence: 49%

“…We investigated the longitudinal development of anti‐JCV antibody status and index in MS patients using predefined short‐termed intervals. This provides the advantage of clearly defined follow‐up periods of JCV testing in all patients, in contrast to recently published data on cohorts, where test intervals had to be defined retrospectively by approximation (Alroughani et al, ; Donovan & LaGanke, ; Hegen et al, ; Plavina et al, ; Vennegoor et al, ). Regarding demographic data, our study represents a typical MS population with a mean age in the midthirties and a predominance of female patients (Pugliatti et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, we wanted to confirm development of anti‐JCV antibody index values over time in a prospective setting, which has been well described in retrospective analyses (Hegen et al, ; Schwab et al, ).…”

Section: Introductionmentioning

confidence: 93%

“…Furthermore, longitudinal observations of multiple JCV testing showed that most patients present stable anti‐JCV antibody status and index values over years, although seroconvertion rates of 5%–33% per year have been described (reviewed by Schwab et al, ). In this context one has to distinguish between patients who fluctuate around the cut‐off index of the ELISA test, by that converting and reverting between anti‐JCV antibody negative and positive although showing index values within a narrow range, and patients who experience a new infection with JCV by converting from negative to persistently positive anti‐JCV antibody index values (Alroughani et al, ; Campagnolo, Ho, & Patel, ; Donovan & LaGanke, ; Hegen et al, ; Plavina et al, ; Vennegoor et al, ). So far, in Natalizumab‐treated MS patients who are negative or low positive for anti‐JCV antibodies, six‐monthly follow‐up tests are recommended by consensus (McGuigan et al, ), in order to detect seroconverters and to discuss treatment continuation in patients with increased risk of PML.…”

Section: Introductionmentioning

confidence: 99%

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Conversion and reversion of anti‐John Cunningham virus antibody serostatus: A prospective study

et al. 2019

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Introduction Determination of antibodies against the John Cunningham virus (JCV) is an important tool for risk stratification in Natalizumab‐treated multiple sclerosis (MS) patients. Six‐monthly testing has been suggested for anti‐JCV antibody negative patients and patients with low antibody index in order to detect changes of serostatus. We conducted a prospective study with predefined testing intervals in order to investigate the predictability of anti‐JCV antibody status and the intervals for repetitive testing. Methods Our study included 109 patients at the MS Clinic of the Departments of Neurology, Medical Universities of Innsbruck and Salzburg. Blood withdrawals were performed at five time points: baseline, month 1, 3, 6, and 12. Patients’ sera were sent to Unilabs, Copenhagen, Denmark, where anti‐JCV antibodies were tested by a two‐step enzyme‐linked immunosorbent assay. Qualitative (negative/positive) and quantitative results (anti‐JCV antibody index) were used for statistical analyses. Results In our cohort, 52.3% of the patients were positive for anti‐JCV antibodies at baseline, with a significant correlation with age, but no association with sex or prior disease‐modifying therapy. Seven patients converted and reverted from negative to positive status and vice versa around the cut‐off index of 0.4, but no patient showed a permanent seroconversion from negative to highly positive anti‐JCV antibody status. Conclusion Long‐term anti‐JCV antibody status, including seroconverters/‐reverters around the cut‐off index, is highly predictable by testing three times within short intervals, however, we cannot suggest clearly defined intervals for repetitive testing. The rate of real seroconverters, i.e., new infections with JCV, per year seems lower than previously described.

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Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus

Bononi

Mazzoni

Pietrobon

et al. 2018

Journal Cellular Physiology

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JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV encodes for the oncoproteins large T antigen (Tag) and small t-antigen (tag). These oncoproteins are responsible of the cell transformation and tumorigenesis in experimental animals. JCPyV is ubiquitous in human populations. After the primary infection, which is usually asymptomatic, JCPyV remains lifelong in the host in a latent phase. Its reactivation may occur in heathy subjects and immunocompromised patients. Upon reactivation, JCPyV could reach (i) the CNS inducing the PML, (ii) the kidney of transplant patients causing the organ rejection. Association between JCPyV, which is a small DNA tumor virus, and gliomas and colorectal carcinomas has been published. In the present investigation, we report on a new indirect ELISA with two specific synthetic peptides mimicking JCPyV VP1 immunogenic epitopes to detect specific serum IgG antibodies against JCPyV. Serum samples of healthy subjects (n = 355) ranging 2-100 years old, were analyzed by this new indirect ELISA. The linear peptides VP1 K and VP1 N resemble the natural JCPyV VP1 capsidic epitopes constituting a docking site for serum antibodies. Data from this innovative immunologic assay indicate that the overall prevalence of JCPyV-VP1 antibodies in healthy subjects is at 39%. The innovative indirect ELISA with JCPyV VP1 mimotopes seems to be a useful method to detect specific IgG antibodies against this virus, without cross-reactivity with the closely related SV40 and BKPyV polyomaviruses.

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Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study

Cited by 28 publications

References 22 publications

Neurological safety of fingolimod: An updated review

Neurological safety of fingolimod: An updated review

Conversion and reversion of anti‐John Cunningham virus antibody serostatus: A prospective study

Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus

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