The risk of developing multiple sclerosis (MS) after infectious mononucleosis (IM) is significantly increased compared to individuals who have never had IM. Infectious mononucleosis, commonly caused by the Epstein-Barr virus (EBV), is a symptomatic manifestation of primary EBV infection, typically occurring during adolescence or adulthood. Studies have shown that people who experience IM have about a two- to threefold higher risk of later developing MS than those who do not have IM.
This increased risk is tied to the role of EBV in MS pathogenesis. EBV infects B-lymphocytes and establishes lifelong persistence in the host. While EBV infection in early childhood is often asymptomatic, infection during adolescence or adulthood frequently results in IM. The immune response triggered during IM appears to set the stage for autoimmune processes that may contribute to MS development years later. Importantly, MS is extremely rare in individuals who remain EBV-negative, underscoring the virus’s critical role in MS risk.
The biological mechanisms linking IM and MS are not fully understood but several hypotheses exist. One theory suggests that EBV-infected B cells may aberrantly activate the immune system, leading to an autoimmune attack on the central nervous system’s myelin sheath, which is characteristic of MS. Another possibility is that EBV antigens mimic components of myelin, causing the immune system to mistakenly target nerve tissue. Elevated antibodies against EBV proteins, especially EBV nuclear antigen-1, have been detected in individuals before MS onset, supporting the idea that EBV infection precedes and possibly triggers MS.
Genetic and environmental factors also influence the risk. For example, individuals with certain genetic backgrounds may be more susceptible to the autoimmune effects of EBV infection. Additionally, the timing of EBV infection matters: early childhood infection tends to be benign, while delayed infection resulting in IM is more strongly associated with MS risk.
Recent research has explored the potential of targeting EBV as a therapeutic strategy for MS. Some existing MS treatments that deplete B cells may work partly by reducing EBV-infected cells. Observations from people living with HIV, who have a lower incidence of MS possibly due to antiretroviral therapies active against EBV, further support the idea that controlling EBV infection could reduce MS risk or severity.
In summary, infectious mononucleosis caused by EBV significantly raises the risk of developing multiple sclerosis later in life, likely due to complex interactions between the virus, the immune system, and genetic factors. This relationship highlights the importance of EBV in MS pathogenesis and opens avenues for preventive and therapeutic approaches focused on EBV control.
