![]() ![]() ĮTX binds to an unknown receptor present both in the brain vasculature and myelinated brain regions e.g. Murrell and colleagues, because of these effects on the CNS, first suggested ETX as a potential MS trigger although humans are not natural hosts for C. visual dysfunction, incoordination and spastic paralysis). ETX is absorbed via the intestine, , –, enters the blood stream and permeabilizes the BBB, resulting in MS like symptoms (e.g. ![]() perfringens toxinotypes B and D are ruminant animals in whom ETX-mediated neurologic symptoms occur when carbohydrate rich feed or over grazing favors exponential growth of the bacilli –. perfringens encoded λ-protease, yielding an active toxin which is ∼1,000X more potent than the protoxin. With log phase growth, protoxin is secreted and cleaved by trypsin and chymotrypsin in the gastrointestinal (GI) tract or by the C. ![]() perfringens types B and D carry the ETX gene, which encodes a 33 kD protoxin –. perfringens is a gram positive, spore forming anaerobe that is sub-categorized into five toxinotypes based on combinatorial carriage of α, β, ε and ι toxins. We reasoned that the environmental trigger for initial lesion formation in MS might be a soluble toxin based on the histopathologic features of the nascent lesion.Ĭ. The absence of an inflammatory infiltrate in nascent lesions argues against MS beginning as an autoimmune phenomenon and instead favors a toxin or viral etiology. In these nascent lesions, demyelination is not yet apparent, there are no lipid-laden macrophages and there is the conspicuous absence of infiltrating lymphocytes –. The earliest lesions studied, fixed hours after onset of symptoms, exhibit blood-brain barrier (BBB) permeability, oligodendrocyte apoptosis, and early microglial activation –. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. Sackler Family Fund for Neuroregenerative Research, The Widgeon Point Charitable Foundation, and the Rockefeller University Funds to the Laboratory of Bacterial Pathogenesis and Immunology. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was generously supported in part by The Laurence Tisch Family Research Fund, The Dr. Received: JanuAccepted: AugPublished: October 16, 2013Ĭopyright: © 2013 Rumah et al. 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.Ĭitation: Rumah KR, Linden J, Fischetti VA, Vartanian T (2013) Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease. 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. The human commensal Clostridium perfringens type A was present in approximately 50% of healthy human controls compared to only 23% in MS patients. perfringens toxinotypes in the gastrointestinal tract. We examined a well-characterized population of MS patients and healthy controls for carriage of C. 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. perfringens type B has been detected in a human. This finding represents the first time that C. 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. ![]()
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