Are highly active and aggressive multiple sclerosis the same entity?

Correale, Jorge; Rush, Carolina; Barboza, Andrés

doi:10.3389/fneur.2023.1132170

Cited by 3 publications

(1 citation statement)

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“…The most common form of MS is relapsing-remitting MS (RRMS), which is characterized by episodes of neurological dysfunction (relapses) followed by periods of full or partial recovery (remission; [3]). RRMS is highly heterogeneous in terms of disease course and symptoms [4] and the evolution of MS seems to be the result of the interplay between acute inflammatory relapses, chronic inflammation in the CNS, the degeneration of axons and loss of oligodendrocytes. Increased resilience in the rates of both axon degeneration and the efficiency of remyelination at early stages of the disease have been proposed to be the basis of the heterogeneous severity found in this clinical MS subtype [5].…”

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confidence: 99%

Circulating Myeloid-Derived Suppressor Cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis

Serrano-Regal,

Camacho-Toledano,

Alonso-García

et al. 2024

Preprint

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BackgroundMultiple sclerosis (MS) is a chronic, inflammatory and demyelinating disease of the central nervous system (CNS) that is highly heterogeneous in terms of disease severity and tissue damage extent. Improving myelin restoration is essential to prevent neurodegeneration and the associated disability in MS patients. However, remyelinating therapies are failing in clinical trials, in part, due to the absence of classifying biomarkers of different endogenous regenerative capacities amongst enrolled patients. We previously reported that circulating monocytic myeloid-derived suppressor cells (M-MDSCs) at the onset of the murine model of MS experimental autoimmune encephalomyelitis (EAE) are associated with milder disease courses and less degree of demyelination and axonal damage in spinal cord lesions, while at peak are indicative of a better symptom recovery. Moreover, M-MDSCs are able to promotein vitrooligodendrocyte precursor cell (OPC) proliferation and differentiation towards mature oligodendrocytes (OLs) through the release of the soluble factor osteopontin.ResultsHere, we show a relationship between disease severity and a gradient of OPCs between the rim and the core in mixed active-inactive lesions of MS patients, along with a positive correlation between M-MDSC density and OPC abundance in the same lesions. We also show that EAE disease severity negatively influences the density of total and newly generated OPCs found associated to the demyelinated lesions of the spinal cord at the peak of the disease. In addition, disease severity also impacts the abundance of newly generated OLs originated either during the effector phase or during the early recovery phase. We also demonstrate the positive association between infiltrated M-MDSCs and the abundance of OPCs in the periplaque of demyelinating lesions at the peak of EAE. Interestingly, circulating M-MDSCs at EAE onset and peak of the disease are directly associated to a higher density of newly generated OLs in the plaque and periplaque, respectively.ConclusionDisease severity clearly impacts oligodendrocyte generation during a neuroinflammatory insult like EAE. Our results set the basis for further studies on M-MDSCs as a promising new biomarker that identify a CNS prone to the generation of new OLs that may contribute to restore myelin.

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confidence: 99%