Study of the anti‐<scp>JCV</scp> antibody levels in a Spanish multiple sclerosis cohort

Domínguez-Mozo, María Inmaculada; Rus, Macarena; Santiago, José Luis; Izquierdo, Guillermo; Casanova, Ignacio; Galán, Victoria; García-Martínez, Mª. Ángel; Arias-Leal, Ana María; García-Montojo, Marta; Pérez-Pérez, Silvia; Arroyo, Rafael; Álvarez‐Lafuente, Roberto

doi:10.1111/eci.12721

Cited by 13 publications

(25 citation statements)

References 27 publications

(66 reference statements)

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“…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%

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: 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: 89%

“…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 ). 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 ).…”

Section: Discussionmentioning

confidence: 89%

“…Prior use of DMTs had no impact on anti-JCV antibody positivity ( 11 – 14 , 16 , 17 ) and index ( 10 ). 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 ).…”

Section: Discussionmentioning

confidence: 92%

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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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“…A previous study reported that Scandinavian and German MS patients with anti-JCV antibodies had a significantly lower frequency of the human leukocyte antigen ( HLA ) -DRB1*15 haplotype than those without anti-JCV antibodies, suggesting the DRB1*15 haplotype is negatively associated with anti-JCV antibody positivity [ 13 ]. A recent Spanish study revealed that older age increased anti-JCV antibody positivity while HLA-DRB1*15:01 carriers had marginally lower anti-JCV antibody positivity rates than DRB1*15:01 non-carriers ( p = 0.056) [ 14 ]. These findings suggest that anti-JCV antibody serostatus are influenced by HLA class II alleles.…”

Section: Introductionmentioning

confidence: 99%

Two susceptible HLA-DRB1 alleles for multiple sclerosis differentially regulate anti-JC virus antibody serostatus along with fingolimod

Watanabe

Nakamura

Isobe

et al. 2020

J Neuroinflammation

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Background Progressive multifocal leukoencephalopathy (PML) caused by JC virus (JCV) is a rare but serious complication of some disease-modifying drugs used to treat multiple sclerosis (MS). Japanese MS patients treated with fingolimod were reported to be 10 times more likely to develop PML than equivalent patients in other countries. The strongest susceptibility human leukocyte antigen ( HLA ) class II alleles for MS are distinct between races ( DRB1*15:01 for Caucasians and DRB1*04:05 and DRB1*15:01 for Japanese); therefore, we investigated whether HLA class II alleles modulate anti-JCV antibody serostatus in Japanese MS patients with and without fingolimod. Methods We enrolled 128 Japanese patients with MS, in whom 64 (50%) were under fingolimod treatment at sampling, and examined the relationship between HLA class II alleles and anti-JCV antibody serostatus. Serum anti-JCV antibody positivity and index were measured using a second-generation two-step assay and HLA-DRB1 and -DPB1 alleles were genotyped. Results HLA-DRB1*15 carriers had a lower frequency of anti-JCV antibody positivity (57% vs 78%, p = 0.015), and lower antibody index (median 0.42 vs 1.97, p = 0.037) than non-carriers. Among patients without HLA-DRB1*15 , DRB1*04 carriers had a higher seropositivity rate than non-carriers (84% vs 54%, p = 0.030), and DPB1*04:02 carriers had a higher anti-JCV antibody index than non-carriers (3.20 vs 1.34, p = 0.008) although anti-JCV antibody-positivity rates did not differ. Patients treated with fingolimod had a higher antibody index than other patients (1.46 vs 0.64, p = 0.039) and treatment period had a positive correlation with antibody index ( p = 0.018). Multivariate logistic regression analysis revealed that age was positively associated, and HLA-DRB1*15 was negatively associated with anti-JCV antibody positivity (odds ratio [OR] = 1.06, p = 0.006, and OR = 0.37, p = 0.028, respectively). Excluding HLA-DRB1*15 -carriers, DRB1*04 was an independent risk factor for the presence of anti-JCV antibody (OR = 5.50, p = 0.023). Conclusions HLA-DRB1*15 is associated with low anti-JCV antibody positive rate and low JCV antibody index, and in the absence of DRB1*15 , DRB1*04 carriers are associ...

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Study of the anti‐JCV antibody levels in a Spanish multiple sclerosis cohort

Abstract: Old age and HLA-DRB115:01 were the factors that influence positively and negatively, respectively, our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB115:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment.

Cited by 13 publications

References 27 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

Two susceptible HLA-DRB1 alleles for multiple sclerosis differentially regulate anti-JC virus antibody serostatus along with fingolimod

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Study of the anti‐JCV antibody levels in a Spanish multiple sclerosis cohort

Abstract: Old age and HLA-DRB1*15:01 were the factors that influence positively and negatively, respectively, our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB1*15:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment.

Cited by 13 publications

References 27 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

Two susceptible HLA-DRB1 alleles for multiple sclerosis differentially regulate anti-JC virus antibody serostatus along with fingolimod

Contact Info

Product

Resources

About

Abstract: Old age and HLA-DRB115:01 were the factors that influence positively and negatively, respectively, our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB115:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment.