Special Issue "The Molecular and Cellular Basis for Multiple Sclerosis - Series 2"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 31 May 2021.

Special Issue Editors

Prof. Dr. Christoph Kleinschnitz
E-Mail Website
Guest Editor
Universitätsklinikum Essen (AöR), Klinik für Neurologie, Hufelandstraße 55, D-45147 Essen, Germany
Interests: neuroimmunology; emphasis on Multiple Sclerosis; stroke (experimental/clinical); thromboinflammation; immune system/inflammation; neuroprotection; cellular and molecular neuroimaging by magnetic resonance imaging
Special Issues and Collections in MDPI journals
Prof. Dr. Sven G. Meuth
E-Mail Website
Guest Editor
Dr. Refik Pul
E-Mail Website
Guest Editor
Universitätsklinikum Essen (AöR), Klinik für Neurologie, Hufelandstraße 55, D-45147 Essen, Germany
Interests: neuroimmunology; multiple sclerosis; animal models; glial cells; neuroimaging; biomarkers in MS
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease. Despite extensive research, the question of whether it is triggered by an initial event outside the CNS (outside–in hypothesis) or whether it is a CNS-intrinsic event (inside–out hypothesis) is still not resolved. The discovery of several molecular and cellular mechanisms has provided valuable insight into the disease mechanism of multiple sclerosis (MS). The former concept that inflammation is only confined to white matter lesions and that autoreactive CD4+ T cells are the exclusive disease contributors no longer holds true. MS is a systemic disease that affects both the grey and white matter of the central nervous system (CNS). Inflammatory and degenerative mechanisms take place at the same time, and their balance probably determines a relapsing–remitting or a progressive disease course. It remains elusive whether primary progressive MS is a disease entity of its own or merely a disease phenotype that lacks superimposed high-grade inflammatory mechanisms. The same question is valid for highly active MS with tumefactive lesions, and the question arises whether there is a molecular key that determines an excessive or a more subtle immune response. Recent research reveals that it does not seem to be a single mechanism, and that there is a need to discover and classify inflammatory molecular and cellular patterns. Understanding these patterns and their dynamics in association with clinical and imaging data will be of utmost importance in deciphering disease mechanisms. In contrast to inflammation, our knowledge about axonal and neural degeneration is quite more restricted. It has been shown that mechanisms underlying neurodegeneration, at least in the long term, proceed autonomously and may be the central pathological feature. The elucidation of emerging cellular and molecular pathways and their relationship to demyelination and inflammation will herald a breakthrough in our understanding of the disease and in developing targeted therapies for neurodegeneration. Moreover, the significant progress made in analyzing genetic risk factors by using genome-wide association studies may not only help to shed light on individual susceptibility and environmental risk factors to develop the disease but also to unravel supervisory roles at the genetic and epigenetic level. More than 150 single nucleotide polymorphisms (SNP) outside the human leucocyte antigen (HLA) system have been discovered and mostly implicate immune genes. For most of the genes located at those SNPs, it must first be verified whether they are functionally relevant at all.

The inclusion of the oligoclonal bands (OCBs) in the new 2017 revised McDonald criteria supports the concept of early diagnosis and treatment but also underlines the need of further molecular and cellular predictors in MS. The current spotlight is on the soluble neurofilament light chain as a disease marker with the capability to follow the footsteps of OCBs. Indeed, there is an urgent need for molecular and cellular biomarkers not only to evaluate MS therapies but also to fill the gap between relapses and MRI lesions. A biomarker that exactly displays the inflammatory and degenerative components of the disease will enable an exactly adapted therapy without losing time in treatment optimization and without hesitation in the treatment of special conditions like radiologically isolated syndrome.

It is fascinating to see how many new drugs have been approved for MS in the last years. Changing the focus to B cells or the idea to “grow a healthier” or more anti-inflammatory immune system after cell depletion are new treatment approaches, but molecular and cellular mechanisms that may explain their effects are lacking. Research focused on the mode of action of MS drugs is of great interest, since it is inevitably associated with the unveiling of disease mechanisms.

This Special Issue is dedicated to the description of pathological cellular and molecular mechanisms, the identification of the fundamental basis of the disease, and the development of molecular interventions to prevent or treat them towards a molecular medicinal perspective of MS.

Prof. Dr. Christoph Kleinschnitz
Prof. Dr. Sven G. Meuth
Dr. Refik Pul
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiple sclerosis
  • demyelination
  • remyelination
  • inflammation
  • neurodegeneration
  • biomarker
  • disease mechanism
  • mode of action of MS drugs

Published Papers (1 paper)

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Research

Open AccessArticle
Cerebrospinal Fluid Biomarkers in Relation to MRZ Reaction Status in Primary Progressive Multiple Sclerosis
Cells 2020, 9(12), 2543; https://doi.org/10.3390/cells9122543 - 25 Nov 2020
Viewed by 692
Abstract
The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS [...] Read more.
The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS (PPMS) but its pathophysiological and wider clinical relevance is unclear. This study aimed to investigate whether PPMS patients with a positive MRZR (MRZR+) differ from those with a negative MRZR (MRZR-) according to cerebrospinal fluid (CSF) biomarkers of B cell activity, neuroaxonal damage or glial activity, and clinical features. (1) Methods: In a multicenter PPMS cohort (n = 81) with known MRZR status, we measured B cell-activating factor (BAFF), chemokine CXC ligand 13 (CXCL-13), soluble B cell maturation antigen (sBCMA), soluble transmembrane activator and CAML interactor (sTACI), and chitinase-3-like protein 1 (CHI3L1) in the CSF with enzyme-linked immunosorbent assays (ELISAs). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were detected in serum and CSF using single molecule array (SIMOA) technology. (2) Results: MRZR+ patients (45.7% of all PPMS patients) revealed higher levels of NfL in CSF compared to MRZR- patients (54.3%). There were positive correlations between each of sBCMA, sTACI, and intrathecal immunoglobin G (IgG) synthesis. Additionally, NfL concentrations in serum positively correlated with those in CSF and those of GFAP in serum. However, MRZR+ and MRZR- patients did not differ concerning clinical features (e.g., age, disease duration, Expanded Disability Status Scale (EDSS) at diagnosis and follow-up); CSF routine parameters; CSF concentrations of BAFF, CXCL-13, sBCMA, sTACI, CHI3L1, and GFAP; or serum concentrations of GFAP and NfL. (3) Conclusions: In PPMS patients, MRZR positivity might indicate a more pronounced axonal damage. Higher levels of the soluble B cell receptors BCMA and transmembrane activator and CAML interactor (TACI) in CSF are associated with a stronger intrathecal IgG synthesis in PPMS. Full article
(This article belongs to the Special Issue The Molecular and Cellular Basis for Multiple Sclerosis - Series 2)
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