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Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression
Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (T(FH)...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585852/ https://www.ncbi.nlm.nih.gov/pubmed/23469245 http://dx.doi.org/10.1371/journal.pone.0057820 |
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author | Christensen, Jeppe Romme Börnsen, Lars Ratzer, Rikke Piehl, Fredrik Khademi, Mohsen Olsson, Tomas Sørensen, Per Soelberg Sellebjerg, Finn |
author_facet | Christensen, Jeppe Romme Börnsen, Lars Ratzer, Rikke Piehl, Fredrik Khademi, Mohsen Olsson, Tomas Sørensen, Per Soelberg Sellebjerg, Finn |
author_sort | Christensen, Jeppe Romme |
collection | PubMed |
description | Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (T(FH)) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4(+) and CD8(+)T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS(+)T(FH)-cells in peripheral blood from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 T(FH)-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 T(FH)-cells. The Th17-subset, interleukin-23-receptor(+)CD4(+)T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN(+) and CD83(+)B-cells in SPMS. ICOS(+)T(FH)-cells and DC-SIGN(+)B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4(+)T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients) had increased expression of T(FH)-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated T(FH)-cells in MS. The increased frequencies of Th17-cells, activated T(FH)- and B-cells parallel findings from pathology studies which, along with the correlation between activated T(FH)- and B-cells and disease progression, suggest a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS. |
format | Online Article Text |
id | pubmed-3585852 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35858522013-03-06 Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression Christensen, Jeppe Romme Börnsen, Lars Ratzer, Rikke Piehl, Fredrik Khademi, Mohsen Olsson, Tomas Sørensen, Per Soelberg Sellebjerg, Finn PLoS One Research Article Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (T(FH)) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4(+) and CD8(+)T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS(+)T(FH)-cells in peripheral blood from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 T(FH)-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 T(FH)-cells. The Th17-subset, interleukin-23-receptor(+)CD4(+)T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN(+) and CD83(+)B-cells in SPMS. ICOS(+)T(FH)-cells and DC-SIGN(+)B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4(+)T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients) had increased expression of T(FH)-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated T(FH)-cells in MS. The increased frequencies of Th17-cells, activated T(FH)- and B-cells parallel findings from pathology studies which, along with the correlation between activated T(FH)- and B-cells and disease progression, suggest a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS. Public Library of Science 2013-03-01 /pmc/articles/PMC3585852/ /pubmed/23469245 http://dx.doi.org/10.1371/journal.pone.0057820 Text en © 2013 Romme Christensen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Christensen, Jeppe Romme Börnsen, Lars Ratzer, Rikke Piehl, Fredrik Khademi, Mohsen Olsson, Tomas Sørensen, Per Soelberg Sellebjerg, Finn Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression |
title | Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression |
title_full | Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression |
title_fullStr | Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression |
title_full_unstemmed | Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression |
title_short | Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression |
title_sort | systemic inflammation in progressive multiple sclerosis involves follicular t-helper, th17- and activated b-cells and correlates with progression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585852/ https://www.ncbi.nlm.nih.gov/pubmed/23469245 http://dx.doi.org/10.1371/journal.pone.0057820 |
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