Genetic regulation of IL-8 influences disease presentation of multiple sclerosis

Author:

Dolcetti Ettore1,Bruno Antonio1,Azzolini Federica1,Gilio Luana1,Pavone Luigi1,Iezzi Ennio1,Galifi Giovanni1,Gambardella Stefano2,Ferese Rosangela1,Buttari Fabio1,De Vito Francesca1,Colantuono Paola3,Furlan Roberto4ORCID,Finardi Annamaria4,Musella Alessandra5,Mandolesi Georgia5,Centonze Diego6,Stampanoni Bassi Mario1

Affiliation:

1. IRCSS Neuromed, Pozzilli, Italy

2. IRCSS Neuromed, Pozzilli, Italy/Department of Biomolecular Sciences, University of Urbino “Carlo Bo,” Urbino, Italy

3. Department of Medicine and Health Sciences “Vincenzo Tiberio,” Unimol, Campobasso, Italy

4. Clinical Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Hospital, Milan, Italy

5. Synaptic Immunopathology Lab, IRCCS San Raffaele Roma, Roma, Italy/Department of Human Sciences and Quality of Life Promotion, University of Rome San Raffaele, Rome, Italy

6. IRCSS Neuromed, Pozzilli, Italy/Department of Systems Medicine, Tor Vergata University, Rome, Italy

Abstract

Background: Individual genetic variability may influence the course of multiple sclerosis (MS). The interleukin (IL)-8C>T rs2227306 single nucleotide polymorphism (SNP) regulates IL-8 activity in other clinical conditions; however, its role in MS has never been investigated. Objectives: To explore the association between IL-8 SNP rs2227306, cerebrospinal fluid (CSF) IL-8 concentrations, clinical, and radiological characteristics in a group of newly diagnosed MS patients. Methods: In 141 relapsing-remitting (RR)-MS patients, rs2227306 polymorphism, CSF levels of IL-8, clinical, and demographical characteristics were determined. In 50 patients, structural magnetic resonance imaging (MRI) measures were also assessed. Results: An association between CSF IL-8 and Expanded Disability Status Scale (EDSS) at diagnosis was found in our set of patients ( r = 0.207, p = 0.014). CSF IL-8 concentrations were significantly higher in patients carrying the T variant of rs2227306 ( p = 0.004). In the same group, a positive correlation emerged between IL-8 and EDSS ( r = 0.273, p = 0.019). Finally, a negative correlation between CSF levels of IL-8 and cortical thickness emerged in rs2227306T carriers ( r = −0.498, p = 0.005). Conclusion: We describe for the first time a role of SNP rs2227306 of IL-8 gene in regulating the expression and the activity of this inflammatory cytokine in MS.

Funder

Project ‘Nuovi Biomarker Diagnostici e Terapeutici delle Malattie Neurodegenerative’—ADOPT co-funded by FOE 2020

Ministero della Salute

Fondazione Italiana Sclerosi Multipla

5 per mille

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

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