A study has revealed how white blood cells in the body react to the Epstein-Barr virus (EBV) in a way that drives autoimmunity in multiple sclerosis (MS), which could help identify and design effective therapies for the condition.
The findings, in Science Translational Medicine, shine a light on immune mechanisms underlying the well-established link between infection with the virus and MS.
Nearly all MS patients are seropositive for EBV, a widespread virus that commonly causes glandular fever otherwise known as infectious mononucleosis.
The research suggests T helper cells in the immune system—also called CD4+ cells—primarily react to particular EBV viral components.
These responses were reduced by B cell depletion therapy, which has known MS therapeutic benefit, suggesting it may be particularly useful for the disease.
“By identifying a readily measurable, peripherally accessible immune response linked to disease, this work provides a foundation for the rational design and monitoring of EBV-targeted vaccines and antivirals for MS,” added the researchers.
MS is a chronic inflammatory disease in which the central nervous system is attacked by the body’s own immune system, damaging the fatty myelin sheath protecting nerves and causing other harm that can affect vision, movement and cognition.
Kjetil Bjornevik, PhD, from Harvard T. H. Chan School of Public health in Boston, and colleagues examined how the virus could affect immune responses by studying healthy individuals, people with treatment-naive MS, and those with MS receiving disease-modifying therapies.
The team found that the CD4+ T cells in the group with MS predominantly targeted several viral components, in particular the late lytic capsid and glycoprotein antigens that are components of EBV viral particles.
The EBV-specific CD4+ T cell response in untreated MS patients was twice that of healthy control individuals, further implicating this response. Responses to other herpes viruses remained similar, suggesting a specific role for EBV in MS immunopathology.
B cell depletion therapy based on anti-CD20 antibodies reduced CD4+ T cell responses to the virus 2.5-fold in two MS groups comprising a total of 69 patients. It also eliminated detectable viral shedding in saliva, consistent with B cells serving as the primary viral reservoir.
The authors concluded: “Together, our findings establish EBV viral particle antigens as the dominant targets of CD4+ T cell responses in MS and demonstrate that these responses are modifiable by current therapies.”
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