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Genome-Wide Multiple Sclerosis Association Data and Coagulation
The emerging concept of a crosstalk between hemostasis, inflammation, and immune system prompt recent works on coagulation cascade in multiple sclerosis (MS). Studies on MS pathology identified several coagulation factors since the beginning of the disease pathophysiology: fibrin deposition with bre...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383413/ https://www.ncbi.nlm.nih.gov/pubmed/30837932 http://dx.doi.org/10.3389/fneur.2019.00095 |
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author | La Starza, Sara Ferraldeschi, Michela Buscarinu, Maria Chiara Romano, Silvia Fornasiero, Arianna Mechelli, Rosella Umeton, Renato Ristori, Giovanni Salvetti, Marco |
author_facet | La Starza, Sara Ferraldeschi, Michela Buscarinu, Maria Chiara Romano, Silvia Fornasiero, Arianna Mechelli, Rosella Umeton, Renato Ristori, Giovanni Salvetti, Marco |
author_sort | La Starza, Sara |
collection | PubMed |
description | The emerging concept of a crosstalk between hemostasis, inflammation, and immune system prompt recent works on coagulation cascade in multiple sclerosis (MS). Studies on MS pathology identified several coagulation factors since the beginning of the disease pathophysiology: fibrin deposition with breakdown of blood brain barrier, and coagulation factors within active plaques may exert pathogenic role, especially through the innate immune system. Studies on circulating coagulation factors showed complex imbalance involving several components of hemostasis cascade (thrombin, factor X, factor XII). To analyze the role of the coagulation process in connection with other pathogenic pathways, we implemented a systematic matching of genome-wide association studies (GWAS) data with an informative and unbiased network of coagulation pathways. Using MetaCore (version 6.35 build 69300, 2018) we analyzed the connectivity (i.e., direct and indirect interactions among two networks) between the network of the coagulation process and the network resulting from feeding into MetaCore the MS GWAS data. The two networks presented a remarkable over-connectivity: 958 connections vs. 561 expected by chance; z-score = 17.39; p-value < 0.00001. Moreover, genes coding for cluster of differentiation 40 (CD40) and plasminogen activator, urokinase (PLAU) shared both networks, pointed to an integral interplay between coagulation cascade and main pathogenic immune effectors. In fact, CD40 pathways is especially operative in B cells, that are currently a major therapeutic target in MS field. The potential interaction of PLAU with a signal of paramount importance for B cell pathogenicity, such as CD40, suggest new lines of research and pave the way to implement new therapeutic targets. |
format | Online Article Text |
id | pubmed-6383413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63834132019-03-05 Genome-Wide Multiple Sclerosis Association Data and Coagulation La Starza, Sara Ferraldeschi, Michela Buscarinu, Maria Chiara Romano, Silvia Fornasiero, Arianna Mechelli, Rosella Umeton, Renato Ristori, Giovanni Salvetti, Marco Front Neurol Neurology The emerging concept of a crosstalk between hemostasis, inflammation, and immune system prompt recent works on coagulation cascade in multiple sclerosis (MS). Studies on MS pathology identified several coagulation factors since the beginning of the disease pathophysiology: fibrin deposition with breakdown of blood brain barrier, and coagulation factors within active plaques may exert pathogenic role, especially through the innate immune system. Studies on circulating coagulation factors showed complex imbalance involving several components of hemostasis cascade (thrombin, factor X, factor XII). To analyze the role of the coagulation process in connection with other pathogenic pathways, we implemented a systematic matching of genome-wide association studies (GWAS) data with an informative and unbiased network of coagulation pathways. Using MetaCore (version 6.35 build 69300, 2018) we analyzed the connectivity (i.e., direct and indirect interactions among two networks) between the network of the coagulation process and the network resulting from feeding into MetaCore the MS GWAS data. The two networks presented a remarkable over-connectivity: 958 connections vs. 561 expected by chance; z-score = 17.39; p-value < 0.00001. Moreover, genes coding for cluster of differentiation 40 (CD40) and plasminogen activator, urokinase (PLAU) shared both networks, pointed to an integral interplay between coagulation cascade and main pathogenic immune effectors. In fact, CD40 pathways is especially operative in B cells, that are currently a major therapeutic target in MS field. The potential interaction of PLAU with a signal of paramount importance for B cell pathogenicity, such as CD40, suggest new lines of research and pave the way to implement new therapeutic targets. Frontiers Media S.A. 2019-02-14 /pmc/articles/PMC6383413/ /pubmed/30837932 http://dx.doi.org/10.3389/fneur.2019.00095 Text en Copyright © 2019 La Starza, Ferraldeschi, Buscarinu, Romano, Fornasiero, Mechelli, Umeton, Ristori and Salvetti. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology La Starza, Sara Ferraldeschi, Michela Buscarinu, Maria Chiara Romano, Silvia Fornasiero, Arianna Mechelli, Rosella Umeton, Renato Ristori, Giovanni Salvetti, Marco Genome-Wide Multiple Sclerosis Association Data and Coagulation |
title | Genome-Wide Multiple Sclerosis Association Data and Coagulation |
title_full | Genome-Wide Multiple Sclerosis Association Data and Coagulation |
title_fullStr | Genome-Wide Multiple Sclerosis Association Data and Coagulation |
title_full_unstemmed | Genome-Wide Multiple Sclerosis Association Data and Coagulation |
title_short | Genome-Wide Multiple Sclerosis Association Data and Coagulation |
title_sort | genome-wide multiple sclerosis association data and coagulation |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383413/ https://www.ncbi.nlm.nih.gov/pubmed/30837932 http://dx.doi.org/10.3389/fneur.2019.00095 |
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