Abstract
The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC) positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.
Highlights
Multiple sclerosis (MS) is the most frequent chronic inflammatory disease of the central nervous system (CNS)
Results of routine cerebrospinal fluid (CSF) examination were consistent with the final diagnosis of relapsing-remitting MS (RRMS) in each patient and all the samples were available for analysis
In the overall control population composed by OIND + NIND, 8 samples obtained from 7 out of 51 (13.7%) subjects had quantifiable EBNA-1 DNA in CSF (4 in cell-free CSF and 4 in CSF pellet, with two positive samples coming from the same NIND patient) and 19 (37.3%) had positive blood samples (3 plasma and peripheral blood mononuclear cells (PBMC) samples from patients), as shown in Table 2 and S1
Summary
Multiple sclerosis (MS) is the most frequent chronic inflammatory disease of the central nervous system (CNS). A recent focused experts workshop on the detection of EBV in MS brain [19] highlighted the possibility that divergent results may be due, at least in part, to technical issues, including methodological approaches and differences in the sensitivity and specificity of the various, mostly ‘‘in house’’, detection assays used. These conclusions are likely to apply to CSF studies
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