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Viremia preceding multiple sclerosis: Two nested case-control studies.

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This study investigated infections in Multiple Sclerosis (MS) using metagenomic sequencing. While Anelloviridae viruses were more common in MS cases before diagnosis in one cohort, this association was not replicated, suggesting potential statistical artifact.

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Area of Science:

  • Infectious Disease Epidemiology
  • Neuroimmunology
  • Metagenomics

Background:

  • Growing evidence suggests a potential role for infectious agents in the etiology of Multiple Sclerosis (MS).
  • Metagenomic sequencing offers a powerful approach to identify known and novel microorganisms associated with diseases.
  • Previous studies have explored viral associations with MS, necessitating further investigation in well-defined cohorts.

Purpose of the Study:

  • To investigate the association between microbial infections, specifically Anelloviridae, and Multiple Sclerosis (MS) using metagenomic sequencing.
  • To analyze serum samples from nested case-control studies to identify microorganisms present before MS diagnosis.
  • To validate initial findings of Anelloviridae association with MS in an independent cohort.

Main Methods:

  • Conducted two nested case-control studies involving registry-linked cohorts for MS.
  • Utilized metagenomic sequencing on serum samples collected from MS cases and matched controls, including samples taken up to two years prior to diagnosis.
  • Analyzed viral reads, focusing on Anelloviridae, and performed statistical comparisons between cases and controls.

Main Results:

  • In the first cohort (75 cases, 75 controls), a significant overrepresentation of Anelloviridae-related viral reads was observed in MS cases.
  • Specific Anellovirus species (TTMV1, TTMV6, TTV27) were found to be significantly more common in cases with samples taken up to two years before MS diagnosis.
  • The second cohort (93 cases, 93 controls) did not replicate the significant case-control difference for Anelloviridae, despite similar viral read profiles.

Conclusions:

  • The observed association between Anelloviridae and Multiple Sclerosis in the initial cohort may be a result of multiple hypothesis testing.
  • While the findings suggest a potential statistical artifact, other explanations for the initial association cannot be entirely excluded.
  • Further research is warranted to elucidate the complex interplay between infections and MS pathogenesis.