Quantitative Detection of Epstein-Barr Virus DNA in Cerebrospinal Fluid and Blood Samples of Patients with Relapsing-Remitting Multiple Sclerosis

OBJECTIVE: To determine if the presence of oligoclonal bands (OB) at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB. METHODS: Relapsing-remitting multiple sclerosis (RRMS) patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF) were included. SIENAX was used for total brain volume (TBV), gray matter volume (GMV), and white matter volume (WMV). RESULTS: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS), treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6) compared with 1.64 mm³ x 10(6) in the negative ones (p=0.02). GMV was 0.51 mm³ x 10(6) in positive IgG-OB compared with 0.62 mm³ x 10(6) in negative ones (p=0.002). No differences in WMV (p=0.09) were seen. CONCLUSIONS: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR) markers in early RRMS.

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Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein–Barr virus in relapsing-remitting multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458516654310 ◽

2016 ◽

Vol 23 (3) ◽

pp. 395-402 ◽

Cited By ~ 32

Author(s):

Egil Røsjø ◽

Andreas Lossius ◽

Nada Abdelmagid ◽

Jonas C Lindstrøm ◽

Margitta T Kampman ◽

...

Keyword(s):

Vitamin D ◽

Epstein Barr Virus ◽

High Dose ◽

Oral Vitamin ◽

Barr Virus ◽

Relapsing Remitting ◽

Dose Oral ◽

Epstein Barr ◽

Antibody Levels ◽

Relapsing Remitting Multiple Sclerosis

Background: Elevated antibody levels against Epstein–Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. Objectives: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. Methods: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385–420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Results: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV. Conclusion: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

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Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510368051 ◽

2010 ◽

Vol 16 (7) ◽

pp. 883-887 ◽

Cited By ~ 19

Author(s):

Massimiliano Castellazzi ◽

Carmine Tamborino ◽

Alice Cani ◽

Elena Negri ◽

Eleonora Baldi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Neurological Disorders ◽

Epstein Barr Virus ◽

Serum Levels ◽

Nuclear Antigen ◽

Enzyme Linked Immunosorbent Assay ◽

Barr Virus ◽

Epstein Barr ◽

Multiple Sclerosis Patients

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

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