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Seropositivity against rubella virus envelope protein 1, but not 2, is associated with an increased risk of multiple

Jens Ingvarsson1, Viktor Grut1, Martin Biström1

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

Clinical & Translational Immunology
|April 20, 2026
PubMed
Abstract

Insights

Rubella virus (RV) E1 antibodies are linked to increased multiple sclerosis (MS) risk, even after accounting for other viruses. This suggests RV may play a role in MS development, preceding axonal injury.

Area of Science:

  • Neurology
  • Virology
  • Immunology

Background:

  • Multiple sclerosis (MS) risk is influenced by various factors, including Epstein-Barr virus (EBV), human herpesvirus 6A (HHV-6A), and cytomegalovirus (CMV).
  • Previous research indicated a potential association between rubella virus (RV) envelope protein 1 (E1) seropositivity and MS risk.

Purpose of the Study:

  • To investigate the association between rubella virus (RV) envelope protein 1 (E1) and envelope protein 2 (E2) seropositivity and the risk of developing multiple sclerosis (MS).
  • To explore the temporal relationship between RV E1 seroreactivity and axonal injury markers in MS cases.

Main Methods:

  • Analysis of pre-onset bio-banked blood samples from 981 MS cases and 1278 matched controls.
  • Assays for antibodies against RV E1 and E2, and serum-neurofilament light chain (S-NfL).
  • Conditional logistic regression used to analyze the association between RV serostatus and MS risk, adjusting for other viral infections.

Main Results:

  • Rubella E1 seropositivity was significantly associated with an increased risk of MS (OR=1.67, P<0.001), independent of EBV, CMV, and HHV-6A status.
  • Increased RV E1 seroreactivity was observed to precede elevations in S-NfL, suggesting it occurs before axonal injury in the MS prodrome.
  • No association was found between RV E2 serostatus and MS risk.

Conclusions:

  • The findings support the broadening of the viral hypothesis in multiple sclerosis etiology.
  • Further research into the neurotropic potential of rubella virus in MS pathogenesis is warranted.
Keywords:
multiple sclerosisneurofilament light‐chainrubella virusserologyvaccination

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