A single nucleotide ADA genetic variant is associated to central inflammation and clinical presentation in MS: Implications for cladribine treatment

Mario Stampanoni Bassi, Fabio Buttari, Ilaria Simonelli, Luana Gilio, Roberto Furlan, Annamaria Finardi, Girolama Alessandra Marfia, Andrea Visconti, Andrea Paolillo, Marianna Storto, Stefano Gambardella, Rosangela Ferese, Marco Salvetti, Antonio Uccelli, Giuseppe Matarese, Diego Centonze, Francesca De Vito

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1152
Pages (from-to)1-12
Number of pages12
JournalGenes
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 2020

Keywords

  • ADA
  • Cladribine tablets
  • IL-10
  • Inflammation
  • Multiple sclerosis
  • TNF

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'A single nucleotide ADA genetic variant is associated to central inflammation and clinical presentation in MS: Implications for cladribine treatment'. Together they form a unique fingerprint.

Cite this