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Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis

In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes i...

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Autores principales: Carstensen, Mikkel, Christensen, Tove, Stilund, Morten, Møller, Holger J, Petersen, Eva L, Petersen, Thor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496724/
https://www.ncbi.nlm.nih.gov/pubmed/32253768
http://dx.doi.org/10.1111/imcb.12337
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author Carstensen, Mikkel
Christensen, Tove
Stilund, Morten
Møller, Holger J
Petersen, Eva L
Petersen, Thor
author_facet Carstensen, Mikkel
Christensen, Tove
Stilund, Morten
Møller, Holger J
Petersen, Eva L
Petersen, Thor
author_sort Carstensen, Mikkel
collection PubMed
description In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes into the CNS mediating demyelination and tissue destruction. In the periphery, monocytes are divided into three subsets depending on expression of CD14 and CD16, representing different stages of activation and differentiation. To investigate their involvement in MS, peripheral blood mononuclear cells (PBMCs) from 61 patients with incipient, untreated MS and 22 symptomatic control (SC) patients as well as 6 patients with radiologically isolated syndrome (RIS) were characterized ex vivo. In addition, paired serum and cerebrospinal fluid (CSF) samples were analyzed with a panel of biomarkers. In PBMC samples, we demonstrate decreased levels of nonclassical monocytes with a concomitant significant decrease of human endogenous retrovirus (HERV) H3 envelope epitopes on this monocyte subset compared with SC and RIS. The observed HERV expression is present on nonclassical monocytes irrespective of MS and thus presumably a result of the inflammatory activation. For the other surface markers analyzed, we found significantly decreased expression between classical and nonclassical monocytes. In matched samples of CSF a highly significant increase in levels of soluble markers of activation and inflammation is shown, and notably this is not the case for the serum samples. Of the soluble markers investigated, interleukin (IL)‐12/IL‐23p40 had the highest discriminatory power in differentiating patients with MS from SC and RIS, almost comparable to the immunoglobulin G index.
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spelling pubmed-74967242020-09-25 Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis Carstensen, Mikkel Christensen, Tove Stilund, Morten Møller, Holger J Petersen, Eva L Petersen, Thor Immunol Cell Biol Original Articles In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes into the CNS mediating demyelination and tissue destruction. In the periphery, monocytes are divided into three subsets depending on expression of CD14 and CD16, representing different stages of activation and differentiation. To investigate their involvement in MS, peripheral blood mononuclear cells (PBMCs) from 61 patients with incipient, untreated MS and 22 symptomatic control (SC) patients as well as 6 patients with radiologically isolated syndrome (RIS) were characterized ex vivo. In addition, paired serum and cerebrospinal fluid (CSF) samples were analyzed with a panel of biomarkers. In PBMC samples, we demonstrate decreased levels of nonclassical monocytes with a concomitant significant decrease of human endogenous retrovirus (HERV) H3 envelope epitopes on this monocyte subset compared with SC and RIS. The observed HERV expression is present on nonclassical monocytes irrespective of MS and thus presumably a result of the inflammatory activation. For the other surface markers analyzed, we found significantly decreased expression between classical and nonclassical monocytes. In matched samples of CSF a highly significant increase in levels of soluble markers of activation and inflammation is shown, and notably this is not the case for the serum samples. Of the soluble markers investigated, interleukin (IL)‐12/IL‐23p40 had the highest discriminatory power in differentiating patients with MS from SC and RIS, almost comparable to the immunoglobulin G index. John Wiley and Sons Inc. 2020-05-05 2020-08 /pmc/articles/PMC7496724/ /pubmed/32253768 http://dx.doi.org/10.1111/imcb.12337 Text en © 2020 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Carstensen, Mikkel
Christensen, Tove
Stilund, Morten
Møller, Holger J
Petersen, Eva L
Petersen, Thor
Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis
title Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis
title_full Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis
title_fullStr Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis
title_full_unstemmed Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis
title_short Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis
title_sort activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496724/
https://www.ncbi.nlm.nih.gov/pubmed/32253768
http://dx.doi.org/10.1111/imcb.12337
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