Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783603308468895744
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
work_keys_str_mv AT stampanonibassimario asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT buttarifabio asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT simonelliilaria asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT gilioluana asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT furlanroberto asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT finardiannamaria asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT marfiagirolamaalessandra asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT viscontiandrea asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT paolilloandrea asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT stortomarianna asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT gambardellastefano asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT fereserosangela asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT salvettimarco asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT uccelliantonio asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT mataresegiuseppe asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT centonzediego asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT devitofrancesca asinglenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT stampanonibassimario singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT buttarifabio singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT simonelliilaria singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT gilioluana singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT furlanroberto singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT finardiannamaria singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT marfiagirolamaalessandra singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT viscontiandrea singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT paolilloandrea singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT stortomarianna singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT gambardellastefano singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT fereserosangela singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT salvettimarco singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT uccelliantonio singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT mataresegiuseppe singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT centonzediego singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment
AT devitofrancesca singlenucleotideadageneticvariantisassociatedtocentralinflammationandclinicalpresentationinmsimplicationsforcladribinetreatment