Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab.

The presence of anti-John Cunningham Virus (JCV) antibodies is a risk factor for the development of progressive multifocal leukoencephalopathy (PML) in MS patients treated with natalizumab. It has been suggested that an increase in serum anti-JCV antibody index precedes the development of PML. We here describe extensive longitudinal serum anti-JCV antibody indexes of four MS patients who developed PML. Anti-JCV antibodies were measured using the STRATIFY JCV™DxSelect™ test. All four patients had rather stable high anti-JCV antibody indexes in all samples obtained before developing PML. Possibly caused by reaching the saturation level of the assay, no increase in anti-JCV antibody indexes was seen just before the diagnosis of PML. This study confirms that high serum anti-JCV antibody indexes precede natalizumab-associated PML.

Download Full-text

Changes in John Cunningham virus index in Multiple Sclerosis patients treated with different disease-modifying therapies

Current Neuropharmacology ◽

10.2174/1570159x19666211111123202 ◽

2021 ◽

Vol 19 ◽

Author(s):

Eleonora Sgarlata ◽

Clara Grazia Chisari ◽

Simona Toscano ◽

Chiara Finocchiaro ◽

Salvatore Lo Fermo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Longitudinal Study ◽

Progressive Multifocal Leukoencephalopathy ◽

Dimethyl Fumarate ◽

John Cunningham Virus ◽

Disease Modifying Therapies ◽

Group A ◽

The Mean ◽

Disease Modifying ◽

Multiple Sclerosis Patients

Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated to natalizumab (NTZ) treatment for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease modifying therapies (DMTs) on JCV index have not been fully explored. Objective: to evaluate changes in JCV index during treatment with several DMTs. Methods: This longitudinal study evaluated JCV index before starting DMT (T0) and on DMT (T1). Results: A total of 260 (65.4% females, mean age 43±11.3 ) were enrolled: 68 (26.2%) treated with fingolimod (FTY), 65 (25%), rituximab or ocrelizumab (RTX/OCR), 37 (14.2%), dimethyl-fumarate (DMF), 29 (11.2%), cladribine (CLD), 23 (8.8%), teriflunomide (TFM), 20 (7.7%), interferon or glatiramer acetate (IFN/GA), and 18 (6.9%) alemtuzumab (ALM). At T1, the percentage of patients with JCV index '0.90 was significantly increased in the ALM group (16.7% versus 66.7%, p=0.05), the percentage of patients with JCV index >1.51 was significantly reduced in RTX/OCR group (51.6% versus 37.5%, p=0.04). In the FTY group, a significant reduction in percentage of patients with JCV index '0.90 was also found (23.5% versus 1.4%, p=0.0006). The mean JCV index was reduced in RTX/OCR and ALM groups, while a significant increase was observed in the FTY group. Conclusion: DMTs with a T and/or B depleting mechanism of action induced a significant reduction of the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control, while reducing PML risk.

Download Full-text

Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20180083 ◽

2018 ◽

Vol 76 (9) ◽

pp. 588-591 ◽

Cited By ~ 1

Author(s):

Luciana Prats Branco ◽

Tarso Adoni ◽

Samira Luisa Apostolos-Pereira ◽

Joseph Bruno Bidin Brooks ◽

Eber Castro Correa ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Progressive Multifocal Leukoencephalopathy ◽

Immunosorbent Assay ◽

Treatment Options ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Antibodies ◽

John Cunningham Virus ◽

Blood Tests ◽

Serological Profile

ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

Download Full-text

The effect of tonsillectomy on John Cunningham virus serological status in multiple sclerosis patients: A retrospective case–control study

Multiple Sclerosis Journal ◽

10.1177/1352458520971822 ◽

2020 ◽

pp. 135245852097182

Author(s):

Mirla Avila ◽

Annette Okai ◽

Smathorn Thakolwiboon ◽

Collin O’Bryan ◽

Murali Mohan Reddy Gopireddy ◽

...

Keyword(s):

Multiple Sclerosis ◽

Case Control Study ◽

The United States ◽

Case Control ◽

Retrospective Case ◽

John Cunningham Virus ◽

Long Term Effect ◽

And Gender ◽

Multiple Sclerosis Patients ◽

Control Study

Tonsils are believed to be the initial site of the John Cunningham virus (JCV) infection. The long-term effect of childhood tonsillectomy on JCV status in multiple sclerosis (MS) patients has not been investigated. In this retrospective case–control study, we analyzed data of 144 JCV seropositive cases and 82 JCV seronegative controls from three outpatient MS clinics in the United States. Early tonsillectomy (before the age of 8) was reported among 8 (5.56%) JCV seropositive subjects and 19 (23.17%) controls. Early tonsillectomy was associated with JCV negative status (adjusted odds ratio = 5.39, 95% confidence interval = 2.13–13.62, p < 0.001) independent of age and gender.

Download Full-text

Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458514534513 ◽

2014 ◽

Vol 20 (14) ◽

pp. 1851-1859 ◽

Cited By ~ 38

Author(s):

M Muñoz-Culla ◽

H Irizar ◽

T Castillo-Triviño ◽

M Sáenz-Cuesta ◽

L Sepúlveda ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multifocal Leukoencephalopathy ◽

Differential Expression ◽

Expression Pattern ◽

Mirna Expression ◽

Disease Biomarkers ◽

Mirna Expression Pattern ◽

Increased Risk ◽

Relapsing Remitting ◽

Multiple Sclerosis Patients

Background: Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability; however, it has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). The differential expression of microRNA (miRNA), the small non-coding RNAs that regulate gene expression, in natalizumab-treated patients has been reported and miRNA have also been described as good candidates for disease biomarkers. Objective: To characterize the effect of natalizumab therapy on the miRNA expression pattern and to search for miRNAs that can predict PML on an individual basis. Methods: The expression of 754 microRNAs was measured in blood samples from 19 relapsing–remitting MS patients at three time points during natalizumab therapy, using TaqMan OpenArray panels. Two patients included in this study developed PML after more than 2 years of therapy. Results: We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy (t6). Furthermore, we observed a differential expression of another three miRNAs (miR-320, miR-320b and miR-629) between the PML and non-PML groups after 12 months of treatment (t12); and a positive correlation was found between therapy time and the expression of miR-320. Conclusions: Natalizumab modified the expression levels of three miRNAs after a 6-month treatment. We suggest miR-320, miR-320b and miR-629 as possible biomarkers for individual PML risk assessment.

Download Full-text

High prevalence and indexes of anti-John Cunningham virus antibodies in a cohort of Chinese patients with multiple sclerosis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318788699 ◽

2018 ◽

Vol 4 (3) ◽

pp. 205521731878869 ◽

Cited By ~ 1

Author(s):

Alexander Lau ◽

Wei Qiu ◽

Allan Kermode ◽

Cheryl Au ◽

Angel Ng ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cross Sectional Study ◽

Chinese Patients ◽

Virus Antibody ◽

Cross Sectional ◽

John Cunningham Virus ◽

High Prevalence ◽

Scale Scores ◽

Disease Modifying ◽

Multiple Sclerosis Patients

We performed a cross-sectional study in 123 Chinese multiple sclerosis patients residing in Hong Kong to evaluate their anti-John Cunningham virus status using STRATIFY JCV DxSelect assays. Anti-John Cunningham virus antibody was present in 98/123 (80%) subjects, among which 75/98 (77%) had an anti-John Cunningham virus index ≥1.5. Anti-John Cunningham virus antibody seropositivity was not correlated with age, disease duration, Expanded Disability Status Scale scores, types of multiple sclerosis (relapsing vs progressive), or disease-modifying treatments used. We found a very high seroprevalence and index of anti-John Cunningham virus antibodies in Chinese multiple sclerosis patients, which may impact the risk assessment and recommendation of disease-modifying treatments in this population.

Download Full-text