Sunday, January 23, 2022

Epstein Barr Virus Infection May be Associated with the Onset of Multiple Sclerosis

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.

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