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Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis-a presymptomatic case-control

Viktor Grut1, Martin Biström1, Jonatan Salzer1

  • 1Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.

European Journal of Neurology
|June 9, 2021
PubMed
Abstract

Insights

Cytomegalovirus (CMV) infection is linked to a lower risk of developing multiple sclerosis (MS). This protective effect is strengthened by interactions with Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A) infections.

Area of Science:

  • Virology
  • Neuroimmunology
  • Epidemiology

Background:

  • Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A) are implicated in increasing multiple sclerosis (MS) risk.
  • Cytomegalovirus (CMV) infection has been hypothesized to reduce MS risk, but presymptomatic evidence is limited.

Purpose of the Study:

  • To investigate the role of cytomegalovirus (CMV) in the etiology of multiple sclerosis (MS).
  • To clarify the association between CMV seropositivity and MS risk in a presymptomatic cohort.

Main Methods:

  • A nested case-control study utilized presymptomatically collected blood samples from MS registries and biobanks.
  • Serological antibody responses to CMV, EBV, and HHV-6A were measured using a multiplex assay.
  • Conditional logistic regression analyzed the odds ratio (OR) for CMV seropositivity, adjusting for EBV and HHV-6A, and assessed statistical interactions.

Main Results:

  • CMV seropositivity was associated with a significantly reduced risk of MS (OR = 0.70, p = 0.003).
  • Significant statistical interactions were found between CMV seronegativity and HHV-6A seropositivity (AP = 0.34).
  • Interactions were also observed between CMV seronegativity and EBV antigen EBNA-1 seropositivity at ages 20-39 (AP = 0.37).

Conclusions:

  • Cytomegalovirus (CMV) seropositivity is associated with a decreased risk of developing multiple sclerosis (MS).
  • The findings support a protective role for CMV infection in MS etiology.
  • Interactions between CMV seronegativity and seropositivity for EBV and HHV-6A further elucidate CMV's influence on MS risk.
Keywords:
case-control studiescytomegalovirusherpesvirusesmultiple sclerosisserology

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