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Epstein-Barr Virus in the Cerebrospinal Fluid and Blood Compartments of Patients With Multiple Sclerosis and Controls

Joonas Lehikoinen1, Katariina Nurmi1, Mari Ainola1

  • 1From the Translational Immunology Research Program (J.L., K.N., M.A., J.K.N., L.J., S.M.L., K.K.E., P.J.T.), University of Helsinki; Departments of Neurology (J.L., J.K.N., L.J., S.M.L., P.J.T.), Neurocenter, and Rheumatology (K.N., M.A., K.K.E.), Helsinki University Hospital; Research and Development (J.C.), Finnish Red Cross Blood Service, Helsinki; and Department of Virology (H.V., A.V., T.S.), Medicum, University of Helsinki, Finland.

Neurology(R) Neuroimmunology & Neuroinflammation
|April 12, 2024
PubMed
Abstract

Insights

Epstein-Barr virus (EBV) DNA is equally detectable in cerebrospinal fluid (CSF) cells of multiple sclerosis (MS) patients and controls. The proportion of EBV-positive B cells in CSF and blood may be higher than previously thought.

Area of Science:

  • Neuroimmunology
  • Virology
  • Molecular Biology

Background:

  • Epstein-Barr virus (EBV) infection is a significant risk factor for multiple sclerosis (MS).
  • This study investigates the presence and prevalence of EBV DNA in the cerebrospinal fluid (CSF) and blood of MS patients and controls.

Purpose of the Study:

  • To determine if EBV DNA is more common in the CSF of MS patients compared to controls.
  • To estimate the proportions of EBV-positive B cells in both CSF and blood.

Main Methods:

  • Collected CSF and blood samples from 45 MS patients and 45 matched controls, all EBV seropositive.
  • Utilized multiple droplet digital PCR (ddPCR) to detect EBV DNA in CSF cells and blood B cells.
  • Performed RNA sequencing on blood lymphocyte subpopulations to detect viral RNA as a sign of activation.

Main Results:

  • EBV DNA was detected in CSF cells of 64% of MS patients and 54% of controls (p=0.59).
  • A probabilistic approach suggests near 100% EBV positivity in CSF cells of EBV-seropositive individuals.
  • The estimated proportion of EBV-positive B cells in CSF and blood exceeded 1/10,000.

Conclusions:

  • EBV DNA detection in CSF cells using ddPCR is similar between MS patients and controls.
  • The true EBV positivity rate in CSF cells approaches 100% in EBV-seropositive individuals.
  • The prevalence of EBV-positive B cells may be underestimated by previous studies.

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