Anti-JCV antibody serostatus and longitudinal evaluation in a Portuguese Multiple Sclerosis population

Correia, Inês; Jesus‐Ribeiro, Joana; Batista, Sónia; Martins, Andrea; Nunes, Cristina; Macário, Maria Carmo; Cunha, Luı́s; Sousa, Lívia

doi:10.1016/j.jocn.2017.08.006

Cited by 15 publications

(16 citation statements)

References 23 publications

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“…The seroprevalence of anti-JCV antibodies in our cohort (80%) was higher than the overall seroprevalence worldwide (57%) among patients with MS and NMOSD,16 and higher than that found (58%) in large clinical studies of natalizumab-treated MS patients 3. Furthermore, 61% of our total cohort had anti-JCV-antibody indices >1.5, which is much higher than the rates reported for Western cohorts, such as 22% in Germany,8 33% in the UK,7 40% in Spain,5 40% in Portugal,4 and 45% in Austria 6. Previous studies have found that the seropositivity rates are higher in males than in females and increase with age,817 but we did not observe significant differences in serostatus according to sex or age.…”

Section: Discussioncontrasting

confidence: 62%

“…It has been suggested that patients with an anti-JCV-antibody index >1.5 have an increased risk of the subsequent development of PML during natalizumab treatment 2. Data on natalizumab-treated patients pooled from large, open-label studies revealed that about 58% of patients were JCV seropositive3 and that 22–45% of patients in European countries had an index >1.5 45678…”

Section: Introductionmentioning

confidence: 99%

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High Seroprevalence and Index of Anti-John-Cunningham Virus Antibodies in Korean Patients with Multiple Sclerosis

Kim

Jung

et al. 2019

J Clin Neurol

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Background and PurposeThe anti-John-Cunningham virus (JCV)-antibody serostatus and index are used in the risk stratification of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab. However, little information on these parameters is available for Asian countries. The purpose of this study was to determine the rate of seropositivity, index, and longitudinal index evolution in Korean patients with MS.MethodsThe antibody seroprevalence was analyzed in 355 samples from 187 patients with clinically isolated syndrome or MS using a second-generation, two-step, enzyme-linked immunosorbent assay. A 4-year longitudinal evaluation was applied to 66 patients.ResultsThe overall antibody seroprevalence was 80% (n=149). Among antibody-positive patients, the index had a median value of 3.27 (interquartile range, 1.52–4.18), with 77% (n=114) and 56% (n=83) of patients having indices >1.5 and >3.0, respectively. The serostatus of 59 (89%) of the 66 patients did not change during the longitudinal analysis, while 3 (6%) of the 53 patients who were initially seropositive reverted to seronegativity, and 2 (15%) of the 13 patients who were initially seronegative converted to seropositivity. All patients with a baseline index >0.9 maintained seropositivity, and 92% of patients with a baseline index >1.5 maintained this index over 4 years. No patients developed PML (median disease duration, 8 years).ConclusionsThe seroprevalence and index of anti-JCV antibodies in Korean patients with MS may be higher than those in Western countries.

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Section: Discussioncontrasting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

High Seroprevalence and Index of Anti-John-Cunningham Virus Antibodies in Korean Patients with Multiple Sclerosis

Kim

Jung

et al. 2019

J Clin Neurol

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“…In this context, it has to be distinguished whether the influence of the variable of interest (e.g., age) on either anti-JCV antibody status or index was investigated, and it has to be distinguished whether a cross-sectional study design (establishing an association between the variable of interest and anti-JCV antibody status or index) or a longitudinal study design (assessing the change over time, i.e., seroconversion/-reversion or change in anti-JCV AI) was applied. By cross-sectional design, higher anti-JCV antibody prevalence ( 5 , 10 – 17 ) and indices ( 4 , 6 ) were observed with increasing patients' age, as well as in most studies higher antibody prevalence in males ( 5 , 10 – 12 , 14 , 16 , 18 ). Prior use of DMTs had no impact on anti-JCV antibody positivity ( 11 – 14 , 16 , 17 ) and index ( 10 ).…”

Section: Discussionmentioning

confidence: 90%

“…By longitudinal design, age ( 4 ) and baseline anti-JCV AI ( 4 , 19 ) were predictors of later anti-JCV antibody serostatus change, whereas no influence of prior and current DMTs on seroconversion rate were observed ( 14 , 17 ). One study reported an increase in the annual rate of seroconversion with NTZ treatment duration, however, these higher rates were observed at the end of follow-up when the number of patients were small due to high drop-outs (e.g., only 20 of 85 patients remained in the study at year 5) ( 18 ). With respect to longitudinal anti-JCV AI evolution, two recent studies observed an increase of anti-JCV AI while on NTZ therapy ( 6 , 7 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of Disease-Modifying Treatments on the Longitudinal Evolution of Anti-JCV Antibody Index in Multiple Sclerosis

et al. 2018

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Background: Risk of natalizumab-related progressive multifocal leukoencephalopathy is associated with the presence of anti-JC-virus (JCV) antibodies.Objective: To investigate the impact of disease-modifying treatments (DMT) on the longitudinal evolution of anti-JCV antibody index.Methods: Patients with multiple sclerosis who had serum sampling at intervals of 6 ± 3 months over up to 6 years and who either started DMT (interferon-β, glatiramer acetate or natalizumab) during the observation period with at least one serum sample available before and after treatment initiation or received no DMT during the observation period were included. Anti-JCV antibody serological status and index were determined by 2-step second-generation anti-JCV antibody assay.Results: A total of 89 patients were followed for a median time of 55.2 months. Of those, 62 (69.7%) started DMT and 27 (30.3%) were without therapy during the observation period. Variation of longitudinal anti-JCV antibody index ranged from 9 to 15% and was similar in patients with and without DMT. Applying a mixed model considering the combined effects of treatment and time as well as individual heterogeneity did not show a significant change of anti-JCV antibody index by the start of treatment with interferon-β, glatiramer acetate, or natalizumab.Conclusion: Evaluated DMTs do not impact longitudinal anti-JCV antibody index evolution.

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“…Determining whether a patient is seropositive for JCV prior to the start of treatment is recommended; however, the high rate of false negatives in these assays can skew risk assessments ( 16 ). In addition, patients seroconvert at higher frequencies during treatment ( 17 , 18 ). Therefore, it will be necessary to monitor additional parameters throughout the course of treatment to more accurately determine risk.…”

Section: Introductionmentioning

confidence: 99%

Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View

Mills

Mao-Draayer

2018

Front. Immunol.

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The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus. The manifestation of PML requires the presence of an active, genetically rearranged form of the JC virus within CNS glial cells, coupled with the loss of appropriate JC virus-specific immune responses. The reliability of metrics used to predict risk for PML could be improved if all three components, i.e., viral genetic strain, localization, and host immune function, were taken into account. Advances in our understanding of the critical lymphocyte subpopulation changes induced by these MS therapies and ability to detect viral mutation and reactivation will facilitate efforts to develop these metrics.

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Anti-JCV antibody serostatus and longitudinal evaluation in a Portuguese Multiple Sclerosis population

Cited by 15 publications

References 23 publications

High Seroprevalence and Index of Anti-John-Cunningham Virus Antibodies in Korean Patients with Multiple Sclerosis

High Seroprevalence and Index of Anti-John-Cunningham Virus Antibodies in Korean Patients with Multiple Sclerosis

Impact of Disease-Modifying Treatments on the Longitudinal Evolution of Anti-JCV Antibody Index in Multiple Sclerosis

Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View

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