Multiple Sclerosis (MS) is a chronic and debilitating disease that is a result of the destruction of the myelin sheath that serves as insulation for the peripheral nerves within the central nervous system (CNS). The loss of myelin has serious implications for the patient suffering from this syndrome – it results in a gradual deterioration of motor function.
To date the etiology of this disease has been unclear. It has long been suggested that Infection
with the Epstein-Barr virus (EBV) may be responsible for triggering the onset
of MS. In a recent issue of the
prestigious publication Science (January, 2022), Kjetil Bjornevik, from
the Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston,
MA, has provided compelling statistical evidence that EBV infection triggers
the onset of MS. According to the
author, “analyzed EBV antibodies in serum from 801 individuals who developed MS
among a cohort of >10 million people active in the US military over a
20-year period (1993–2013). Thirty-five of the 801 MS cases were initially EBV
seronegative, and 34 became infected with EBV before the onset of MS. EBV
seropositivity was nearly ubiquitous at the time of MS development, with only
one of 801 MS cases being EBV seronegative at the time of MS onset. These
findings provide compelling data that implicate EBV as the trigger for the
development of MS.”
EBV (see diagram below) preferentially attacks B cells; B cells are the part of
the immune system repertoire responsible for the production of antibodies. In MS
the myelin sheath is degraded through an inflammatory response. It has been shown that in MS the B cells responsible
for this inflammatory are derived from plasmablasts that are generated in the
marrow and take residence inside the brain and its internal lining. These plasmablasts divide and produce
clusters of daughter cells that produce immunoglobulins. These immunoglobulins contain specific antibodies
that target myelin-producing glial cells within the central nervous system
(CNS).
EBV Virus
One of the accepted therapies that attempt to take advantage
of this etiology is the use of monoclonal antibodies that target CD20 - a protein
preferentially found on the surface of B cells.
However, it has significant drawbacks in so far as these monoclonals do
not readily pass through the blood brain barrier (BBB) and they are unable to
bind to plasmablasts.
What remains unclear, however, is the mechanism through
which EBV triggers this sequence of events in MS patients. One possibility involves what is referred to
as molecular mimicry in which some EBV proteins may be similar enough in
structure to myelin that the immune system is induced to produce antibodies against
the infected individual’s myelin and CNS antigens – this would represent an
autoimmune response. In addition, EBV
encodes an interleukin-10–like protein, which activates B cells. The author of this study, reports that recent
evidence seems to suggest that molecular mimicry may be the actual mechanism
underlying the association between EBV infection and MS.
The results of these kind intensive studies of the etiology
of MS are extremely important in that the product of this work may finally
produce effective therapies for MS patients.
