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Clostridium perfringens epsilon toxin (ETX) is the third most lethal bacterial toxin and has been suggested to be an environmental trigger of multiple sclerosis, an immune-mediated disease of the human central nervous system. However, ETX cytotoxicity on primary human cells has not been investigated. In this article, we demonstrate that ETX preferentially binds to and kills human lymphocytes expressing increased levels of the myelin and lymphocyte protein MAL. Using flow cytometry, ETX binding was determined to be time and dose dependent and was highest for CD4+ cells, followed by CD8+ and then CD19+ cells. Similar results were seen with ETX-induced cytotoxicity. To determine if ETX preference for CD4+ cells was related to MAL expression, MAL gene expression was determined by RT-qPCR. CD4+ cells had the highest amount of Mal gene expression followed by CD8+ and CD19+ cells. These data indicate that primary human cells are susceptible to ETX and support the hypothesis that MAL is a main receptor for ETX. Interestingly, ETX bindings to human lymphocytes suggest that ETX may influence immune response in multiple sclerosis.

Abstract Background With the adoption of the English language in medical education, a gap in clinical communication may develop in countries where the native language is different from the language of medical education. This study investigates the association between medical education in a foreign language and students’ confidence in their history-taking skills in their native language. Methods This cross-sectional study consisted of a 17-question survey among medical students in clinical clerkships of Lebanese medical schools. The relationship between the language of medical education and confidence in conducting a medical history in Arabic (the native language) was evaluated (n = 457). Results The majority (88.5%) of students whose native language was Arabic were confident they could conduct a medical history in Arabic. Among participants enrolled in the first clinical year, high confidence in Arabic history-taking was independently associated with Arabic being the native language and with conducting medical history in Arabic either in the pre-clinical years or during extracurricular activities. Among students in their second clinical year, however, these factors were not associated with confidence levels. Conclusions Despite having their medical education in a foreign language, the majority of students in Lebanese medical schools are confident in conducting a medical history in their native language.

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.