title: Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease.
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.
authors.affiliation: Tri-Institutional M.D.-Ph.D. Program of Weill Cornell Medical College, Rockefeller University and Memorial Sloan-Kettering Hospital, New York, New York, United States of America ; The Brain and Mind Research Institute and the Department of Neurology, Weill Cornell Medical College, New York, New York, United States of America ; The Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, New York, United States of America.
authors.forename: Kareem Rashid
authors.initials: KR
authors.lastname: Rumah
authors.forename: Jennifer
authors.initials: J
authors.lastname: Linden
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
authors.forename: Timothy
authors.initials: T
authors.lastname: Vartanian
mesh_terms: D000328:Adult; D001427:Bacterial Toxins / Q000276:immunology; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D003016:Clostridium perfringens / Q000276:immunology / Q000302:isolation & purification*; D042783:Endothelial Cells / Q000382:microbiology / Q000473:pathology; D004777:Environment; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000382:microbiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D009186:Myelin Sheath / Q000378:metabolism; D015995:Prevalence; D011485:Protein Binding; D012171:Retinal Vessels / Q000378:metabolism; D055815:Young Adult
chemical_list: D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin