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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Multiple Sclerosis (MS)

The significance of MP in MS has been recently reviewed [98]. Therefore, we here review only some recent work that strikes us as seminal. Among the most intensive studies of MP in MS is that by Verderio et al. [99], a technical tour de force by 20 authors, using two EAEs (animal models of MS). The MP species studied were mainly from microglia/macrophages measured in CSF. Results demonstrate elevation of MP in close association with the evolution of inflammation in the animal models, consistent with results in patients in that report and with an earlier study cited above [37].

A most interesting finding in that report is that a mouse strain (A-SMase KO) known to be resistant to EAE was also deficient in ability to release MP and was also resistant to the inflammatory effects of injecting inflammatory MP [99]. This is persuasive evidence that MP play a decisive role in MS. However, others have shown that MP/exosomes derived from oligodendrocytes can have widely differing effects, suggesting caution in attributing adverse vs. beneficial effects to any given MP phenotype [49]; see also [100]. Nevertheless, it may be interesting to test the effect of inhibitors of MP release on the progression of disease in EAE animal models.

Another highlight concerns the known tendency of progressive MS to remit during pregnancy. Working with an animal model, Gatson et al. initially demonstrated that the active component of this effect was a factor in serum [101] and, in a followup work, identified the serum factor as exosome associated [102]. This discovery could have therapeutic impact, if and when the specifics are delineated. It was recently observed that chronic infection with Staph. aureus also abated progression of EAE (animal model of MS), and the mechanism of benefit was identified [103].

Miscellaneous Others

Neuropsychiatric systemic lupus (NPSLE) was recently shown to be characterized by unusual pattern of MP lineages, of which only monocyte MP were distinctive, others being reduced [104]. The authors do not know if the reduced levels of some phenotypes result in reduced shedding, or increased consumption, possibly sequestered in the brain.

 
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