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A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment
In multiple sclerosis (MS), activated T and B lymphocytes and microglial cells release various proinflammatory cytokines, promoting neuroinflammation and negatively affecting the course of the disease. The immune response homeostasis is crucially regulated by the activity of the enzyme adenosine dea...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601054/ https://www.ncbi.nlm.nih.gov/pubmed/33007809 http://dx.doi.org/10.3390/genes11101152 |
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author | Stampanoni Bassi, Mario Buttari, Fabio Simonelli, Ilaria Gilio, Luana Furlan, Roberto Finardi, Annamaria Marfia, Girolama Alessandra Visconti, Andrea Paolillo, Andrea Storto, Marianna Gambardella, Stefano Ferese, Rosangela Salvetti, Marco Uccelli, Antonio Matarese, Giuseppe Centonze, Diego De Vito, Francesca |
author_facet | Stampanoni Bassi, Mario Buttari, Fabio Simonelli, Ilaria Gilio, Luana Furlan, Roberto Finardi, Annamaria Marfia, Girolama Alessandra Visconti, Andrea Paolillo, Andrea Storto, Marianna Gambardella, Stefano Ferese, Rosangela Salvetti, Marco Uccelli, Antonio Matarese, Giuseppe Centonze, Diego De Vito, Francesca |
author_sort | Stampanoni Bassi, Mario |
collection | PubMed |
description | In multiple sclerosis (MS), activated T and B lymphocytes and microglial cells release various proinflammatory cytokines, promoting neuroinflammation and negatively affecting the course of the disease. The immune response homeostasis is crucially regulated by the activity of the enzyme adenosine deaminase (ADA), as evidenced in patients with genetic ADA deficiency and in those treated with cladribine tablets. We investigated in a group of patients with MS the associations of a single nucleotide polymorphism (SNP) of ADA gene with disease characteristics and cerebrospinal fluid (CSF) inflammation. The SNP rs244072 of the ADA gene was determined in 561 patients with MS. Disease characteristics were assessed at the time of diagnosis; furthermore, in 258 patients, proinflammatory and anti-inflammatory molecules were measured in the CSF. We found a significant association between rs244072 and both clinical characteristics and central inflammation. In C-carriers, significantly enhanced disability and increased CSF levels of TNF, IL-5 and RANTES was observed. In addition, lower CSF levels of the anti-inflammatory cytokine IL-10 were found. Finally, the presence of the C allele was associated with a tendency of increased lymphocyte count. In MS patients, ADA SNP rs244072 is associated with CSF inflammation and disability. The selective targeting of the ADA pathway through cladribine tablet therapy could be effective in MS by acting on a pathogenically relevant biological mechanism. |
format | Online Article Text |
id | pubmed-7601054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76010542020-11-01 A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment Stampanoni Bassi, Mario Buttari, Fabio Simonelli, Ilaria Gilio, Luana Furlan, Roberto Finardi, Annamaria Marfia, Girolama Alessandra Visconti, Andrea Paolillo, Andrea Storto, Marianna Gambardella, Stefano Ferese, Rosangela Salvetti, Marco Uccelli, Antonio Matarese, Giuseppe Centonze, Diego De Vito, Francesca Genes (Basel) Article In multiple sclerosis (MS), activated T and B lymphocytes and microglial cells release various proinflammatory cytokines, promoting neuroinflammation and negatively affecting the course of the disease. The immune response homeostasis is crucially regulated by the activity of the enzyme adenosine deaminase (ADA), as evidenced in patients with genetic ADA deficiency and in those treated with cladribine tablets. We investigated in a group of patients with MS the associations of a single nucleotide polymorphism (SNP) of ADA gene with disease characteristics and cerebrospinal fluid (CSF) inflammation. The SNP rs244072 of the ADA gene was determined in 561 patients with MS. Disease characteristics were assessed at the time of diagnosis; furthermore, in 258 patients, proinflammatory and anti-inflammatory molecules were measured in the CSF. We found a significant association between rs244072 and both clinical characteristics and central inflammation. In C-carriers, significantly enhanced disability and increased CSF levels of TNF, IL-5 and RANTES was observed. In addition, lower CSF levels of the anti-inflammatory cytokine IL-10 were found. Finally, the presence of the C allele was associated with a tendency of increased lymphocyte count. In MS patients, ADA SNP rs244072 is associated with CSF inflammation and disability. The selective targeting of the ADA pathway through cladribine tablet therapy could be effective in MS by acting on a pathogenically relevant biological mechanism. MDPI 2020-09-30 /pmc/articles/PMC7601054/ /pubmed/33007809 http://dx.doi.org/10.3390/genes11101152 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Stampanoni Bassi, Mario Buttari, Fabio Simonelli, Ilaria Gilio, Luana Furlan, Roberto Finardi, Annamaria Marfia, Girolama Alessandra Visconti, Andrea Paolillo, Andrea Storto, Marianna Gambardella, Stefano Ferese, Rosangela Salvetti, Marco Uccelli, Antonio Matarese, Giuseppe Centonze, Diego De Vito, Francesca A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment |
title | A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment |
title_full | A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment |
title_fullStr | A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment |
title_full_unstemmed | A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment |
title_short | A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment |
title_sort | single nucleotide ada genetic variant is associated to central inflammation and clinical presentation in ms: implications for cladribine treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601054/ https://www.ncbi.nlm.nih.gov/pubmed/33007809 http://dx.doi.org/10.3390/genes11101152 |
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