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Clostridium epsilon toxin is excessive in multiple sclerosis and provokes multifocal lesions in mouse models
Anthony T. Reder
Anthony T. Reder
Published May 1, 2023
Citation Information: J Clin Invest. 2023;133(9):e169643. https://doi.org/10.1172/JCI169643.
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Commentary Article has an altmetric score of 19

Clostridium epsilon toxin is excessive in multiple sclerosis and provokes multifocal lesions in mouse models

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Abstract

Multiple sclerosis (MS) is an inflammatory disease of the CNS. In this issue of the JCI, Ma and Sannino et al. show that two strains of intestinal Clostridium perfringens, known to produce epsilon toxin (ETX), were frequently found in patients with MS. Tiny amounts of this toxin added to immunization with myelin antigens provoked MS-like brain lesions in mice. The distribution of these lesions was diffuse, as in MS, in contrast to the spinal cord–restricted lesions of most animal models. ETX bound to endothelial cells of the CNS to enhance immune cell trafficking through the blood-brain barrier into inflammatory brain lessons. ETX also binds to human, but not murine, white blood cells, perhaps altering immune responses. Barrier disruption and changes in immunity due to the toxin could alter the benefits of immune-modulatory MS therapies and are likely to interact with the complex genetics and environmental influences seen in MS.

Authors

Anthony T. Reder

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Figure 1

Clostridium perfringens epsilon toxin modifies brain lesions in EAE and could affect MS.

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Clostridium perfringens epsilon toxin modifies brain lesions in EAE and...
Patients with MS are more likely to carry two strains of intestinal Clostridium perfringens, known to produce ETX. EAE enhanced by ETX shares more similarities to MS pathology than an EAE model that uses the more standard PTX as an endothelial activator. ETX-EAE is characterized by acute lesions in the brain in addition to the spinal cord; whereas PTX-EAE displays acute lesions exclusively in the spinal cord. Fecal transplants from MS patients will worsen EAE, supporting a model whereby pathogenic bacteria from the small intestine promote brain inflammation in MS.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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