Detection of JC virus DNA in cerebrospinal fluid from multiple sclerosis patients

JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), has been proposed as a possible aetiopathogenic factor in multiple sclerosis (MS). We performed a study to search the LT region of JCV genome by nested PCR in cerebrospinal fluid (CSF), peripheral blood mononuclear cell (PBMC) and urine samples collected from 121 MS patients, 24 patients with other neurological disorders (OND), 30 non neurological patients (NND) and in PBMCs and urine of 40 healthy subjects. JCV DNA has been found in the CSF of 11 MS patients (9%) while all the CSFs from the 24 OND and the 30 NND cases were negative. No significant differences have been observed as regard to the frequency of JCV DNA detection in PBMCs and urine between the MS patients and the control groups. Nucleotide sequences analysis of seven JCV CSF isolates showed that five strains were identical the prototypal strain, while the other two had a base mutation (T→C) in 4286 nucleotide (nt). The finding of JCV DNA in the CSF of MS patients suggest that JCV could play a role in the triggering and/or in the maintenance of MS aetiopathogenic process, and therefore it should be taken in consideration when monitoring this disease.

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Cerebrospinal fluid and serum JC virus antibody detection in multiple sclerosis patients treated with natalizumab

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2013.05.009 ◽

2013 ◽

Vol 261 (1-2) ◽

pp. 123-128 ◽

Cited By ~ 8

Author(s):

Jerry Lin ◽

Peggy Bettin ◽

John K. Lee ◽

Joseph K. Ho ◽

Saud A. Sadiq

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Jc Virus ◽

Antibody Detection ◽

Virus Antibody ◽

Multiple Sclerosis Patients

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JC virus in cerebrospinal fluid samples of multiple sclerosis patients at the first demyelinating event

Multiple Sclerosis Journal ◽

10.1177/1352458506073116 ◽

2007 ◽

Vol 13 (5) ◽

pp. 590-595 ◽

Cited By ~ 20

Author(s):

Roberto Alvarez-Lafuente ◽

Marta García-Montojo ◽

Virginia De Las Heras ◽

Manuel Bartolomé ◽

Rafael Arroyo

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Jc Virus ◽

Neurological Diseases ◽

Positive Sample ◽

Viral Loads ◽

Immunological Activation ◽

Viral Particles ◽

Multiple Sclerosis Patients

Objective To evaluate the possible involvement of JC virus (JCV) in the aetiology of multiple sclerosis (MS), through the comparison of DNA prevalences and viral loads of JCV in cerebrospinal fluid (CSF) of MS patients at the first demyelinating event and subjects suffering from other neurological diseases (OND). Methods Seventy-three CSF samples (43 from MS patients at the first demyelinating event, and 30 from patients with OND) were collected; all MS cases were followed up from 1 to 6.7 years after they were diagnosed with clinically definite MS. DNA was extracted and analysed by real-time PCR for the detection of JCV genomes. Results We found JCV DNA in the CSF of two MS patients (4.7%) with a mean viral load of 2.1 and 6.7 copies/mL of CSF. Among the patients of the OND group we did not find any positive sample. We did not find any difference in the course of the disease between MS patients with and without JCV genomes in their CSF along the follow up. Conclusion JCV seems to be only a bystander in the pathology of MS, and the presence of cell-free viral particles could be related to the immunological activation of the disease, mainly during relapses. Multiple Sclerosis 2007; 13: 590-595. http://msj.sagepub.com

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Effects on cerebrospinal fluid biomarkers in multiple sclerosis patients after repeated intrathecal triamcinolone acetonid application

Aktuelle Neurologie ◽

10.1055/s-2007-988026 ◽

2007 ◽

Vol 34 (S 2) ◽

Author(s):

M Abu-Mugheisib ◽

H Tumani ◽

F Kamin ◽

A Apel ◽

W Köhler ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Cerebrospinal Fluid Biomarkers ◽

Multiple Sclerosis Patients

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JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

Journal of Clinical Medicine ◽

10.3390/jcm10091998 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1998

Author(s):

Robert Bonek ◽

Wojciech Guenter ◽

Robert Jałowiński ◽

Anna Karbicka ◽

Anna Litwin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Jc Virus ◽

Dimethyl Fumarate ◽

Risk Category ◽

Seroprevalence Rate ◽

Immunomodulatory Drugs ◽

Cross Sectional ◽

Treatment Type ◽

Multiple Sclerosis Patients ◽

The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

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NRAMP1 Polymorphism and Viral Factors in Sardinian Multiple Sclerosis Patients

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100009173 ◽

2008 ◽

Vol 35 (4) ◽

pp. 491-494 ◽

Cited By ~ 12

Author(s):

Maria Gazouli ◽

Leonardo Sechi ◽

Daniela Paccagnini ◽

Stefano Sotgiu ◽

Giannina Arru ◽

...

Keyword(s):

Multiple Sclerosis ◽

Autoimmune Disease ◽

Promoter Region ◽

Viral Infections ◽

Jc Virus ◽

Allelic Variation ◽

Sardinian Population ◽

Multiple Sclerosis Patients ◽

Viral Sequences

Background:Multiple sclerosis (MS) is believed to be an autoimmune disease occurring in genetically predisposed individuals after an appropriate environmental exposure such as viral infections. Recent studies suggest a significant association between MS and the functional 5’-(GT)n polymorphism in the promoter region of the NRAMP1 gene. In the present study we aimed to evaluate the contribution of the allelic variation in the NRAMP1 promoter to MS susceptibility and to study the role of viral infection in relation to specific NRAMP1 genotypes, in a Sardinian cohort.Methods:Sixty MS patients and 66 healthy individuals were genotyped, and screened for the presence of Epstein-bar virus (EBV) and JC virus (JCV) sequences.Results:Consistent with previous autoimmune disease studies, allele 3 at the functional 5’(GT)n promoter region repeat polymorphism, was significantly overrepresented among MS patients when compared to controls (p=0.02). The EBV and JCV sequences were detected in 8/60 (13.33%) and in 4/60 (6.66%) of MS patients respectively and in 5/66 (7.57%) and in 0/66 of controls.Conclusion:The allelic variation in the NRAMP1 promoter may contribute to MS susceptibility in the Sardinian population. The viral sequences were not confined to a specific NRAMP1 genotype.

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