Lassman review for 2019. Top four MS papers.

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Lassman review for 2019. Top four MS papers.

Post by frodo » Mon Jan 20, 2020 12:51 am ... /2612/2492

1. Neuronal vulnerability and multilineage diversity in multiple sclerosis (Schirmer et al 2019)

The study supports the importance of meningeal inflammation with high B-lymphocyte content for cortical lesions, the heterogeneous astrocyte and microglia activation in the lesions, the loss of oligodendrocytes, the phagocytosis of myelin debris in macrophages during lesion activity and the importance of oxidative injury as a mechanism of neuronal injury. The most innovative finding is that a distinct subpopulation of excitatory neurons is dominantly affected in subpial cortical lesions of MS patients.

2. Epstein-Barr Virus specific CD8 T cells selectively infiltrate the brain in multiple sclerosis and interact locally with virus-infected cells: Clue for a virus driven immunopathological mechanism (Serafini et al 2019)

Multiple sclerosis is regarded by immunologists as an autoimmune disease, driven by T-lymphocytes directed against myelin anti-gen(s). However, attempts to identify an MS-specific autoimmune response have so far failed (Hohlfeld et al 2016). Even when the investigation specifically focused on activated CD8+ T-cells in the MS lesions, no reactivity was found against the classical candidates of myelin directed autoimmunity, but a substantial number of isolated T-cells recognized epitopes from Epstein Barr virus (EBV; Van Nierop et al 2017, Serafini et al 2019). Furthermore, Serafini et al (2019) showed that these EBV reactive T-cells form close contacts with B-lymphocytes expressing epitopes of EBV related proteins, and these T-cells display CD 107 on their surface, suggesting the release of the content of their cytotoxic granules. Overall these data suggest that the chronic inflammatory response in the MS brains may in part be driven by a T-cell response against EBV (Serafini et al 2019).

3. Microglia nodules provide the environment for pathogenic T cells in human encephalitis (Tröscher et al 2019)

In Rasmussen’s encephalitis T-cells which attack neurons and astrocytes (Bauer et al 2012). In the study by Tröscher et al (2019) it is shown that the initial stage of lesion formation is characterized by microglia activation and the formation of microglia nodules, which occurs before the first CD8+ T-cells have entered the brain. It is suspected that the same can happen in MS.

4. Post mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphism (Fransen et al 2020)

More than 200 gene loci have been found associated with disease incidence, each of them with only very little individual impact.
Fransen et al (2020) found that certain variants of immune related genes, which were before shown to be associated with disease severity, were also associated with the proportion of active lesions. The respective genes were in part related to apoptosis (FAS), T-cell activation (CTLA4) or are playing a role both in inflammation and neurodegeneration (CLEC16A). This study provides a first hint on how the genetic background of MS patients may affect pathological outcome of the lesions.

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