Risk for Multiple Sclerosis Associated With Epstein-Barr, Cytomegalovirus Infection

Epstein-Barr virus illustration
Epstein-Barr virus illustration
Investigators strived to determine the association between multiple sclerosis and Epstein-Barr virus or cytomegalovirus infection in certain racial groups.

Evidence recently published in Neurology suggests a strong biologic link between Epstein-Barr virus (EBV) infection and risk for multiple sclerosis (MS).  

Researchers sought to determine whether EBV and/or cytomegalovirus (CMV) seropositivity is associated with MS in blacks and Hispanics, and the extent to which measures of the hygiene hypothesis or breastfeeding might clarify these findings. The association between EBV and CMV with MS has already been demonstrated in Caucasians.

According to the hygiene hypothesis, the current increase in allergic and autoimmune disorders is a result of prevention or delay in the presentation of common, early-life infections, thus suppressing the natural development of the immune system. 

In the current study, incident cases of MS or clinically isolated syndrome (CIS), and matched controls from various racial and ethnic groups were recruited from the Kaiser Permanente Southern California membership. Participants included blacks (111 cases, 128 controls); Hispanics (173 cases, 187 controls); and whites (235 cases, 256 controls).

Epstein-Barr nuclear antigen-1 seropositivity was associated with a significantly increased risk for MS/CIS in all 3 racial/ethnic groups (P <.001 for blacks and whites; P =.02 for Hispanics). CMV seropositivity, in contrast, was associated with a significantly decreased risk for MS/CIS among Hispanics (P =.004), but not among blacks (P =.95) or whites (P =.96).

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Birth in a low- or middle-income country was associated with a significantly lower risk for MS among Hispanics (P =.02), but the effect did not perpetuate once Epstein-Barr nuclear antigen-1 seropositivity was considered. The relationship between CMV and MS in Hispanics did not diminish when breastfeeding was taken into account.

The results of the study demonstrate a strong biologic link between EBV infection and MS risk. Although the association between prior CMV infection and MS risk reinforces the hygiene hypothesis, the inconsistency of this relationship across racial/ethnic groups and between studies suggests a noncausal association.


Langer-Gould A, Wu J, Lucas R, et al. Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: a multiethnic study. Neurology. 2017;89(13):1330-1337.