Isolation of Clostridium Perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease

PLoS One. 2013 Oct 16;8(10):e76359. doi: 10.1371/journal.pone.0076359. eCollection 2013.

Abstract

We have isolated Clostridium perfringens type B, an epsilon toxin-secreting bacillus, from a young woman at clinical presentation of Multiple Sclerosis (MS) with actively enhancing lesions on brain MRI. This finding represents the first time that C. perfringens type B has been detected in a human. Epsilon toxin's tropism for the blood-brain barrier (BBB) and binding to oligodendrocytes/myelin makes it a provocative candidate for nascent lesion formation in MS. We examined a well-characterized population of MS patients and healthy controls for carriage of C. perfringens toxinotypes in the gastrointestinal tract. The human commensal Clostridium perfringens type A was present in approximately 50% of healthy human controls compared to only 23% in MS patients. We examined sera and CSF obtained from two tissue banks and found that immunoreactivity to ETX is 10 times more prevalent in people with MS than in healthy controls, indicating prior exposure to ETX in the MS population. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation since these lesions are characterized by BBB permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacterial Toxins / immunology
  • Brain / pathology
  • Case-Control Studies
  • Clostridium perfringens / immunology
  • Clostridium perfringens / isolation & purification*
  • Endothelial Cells / microbiology
  • Endothelial Cells / pathology
  • Environment*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / microbiology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / microbiology*
  • Multiple Sclerosis / pathology*
  • Myelin Sheath / metabolism
  • Prevalence
  • Protein Binding
  • Retinal Vessels / metabolism
  • Young Adult

Substances

  • Bacterial Toxins
  • Clostridium perfringens epsilon-toxin