Immune Soluble Factors in the Cerebrospinal Fluid of Progressive Multiple Sclerosis Patients Segregate Into Two Groups

Frontiers in Immunology

Daniele Peluso¹  Daniele Michelis²  Chiara Zecca³  Alice Laroni⁴  Elisabetta Volpe⁵  Gloria Donninelli⁵  Laura Brambilla⁷  Renato Mantegazza⁷  Paolo Confalonieri⁷  Valeria Studer⁸ 

[1] Bioinformatics e Biostatistics Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Rome, Italy;Department of Neuroscience, Rehabilitation, Opthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy;Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland;Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, Genova, Italy;Molecular Neuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Rome, Italy;Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, Lugano, Switzerland;Neuroimmunology and Neuromuscular Diseases Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan, Italy;Neurology Department, Martini Hospital, Turin, Italy;

关键词: progressive multiple sclerosis;    cytokines;    chemokines;    expanded disability status scale;    cerebrospinal fluid;   

DOI  :  10.3389/fimmu.2021.633167

来源: DOAJ

【 摘 要 】

Primary-progressive (PP) and secondary-progressive (SP) multiple sclerosis (MS) are characterized by neurological deficits caused by a permanent neuronal damage, clinically quantified by the expanded disability status scale (EDSS). Neuronal tissue damage is also mediated by immune infiltrates producing soluble factors, such as cytokines and chemokines, which are released in the cerebrospinal fluid (CSF). The mechanisms regulating the production of a soluble factor are not completely defined. Using multiplex bead-based assays, we simultaneously measured 27 immune soluble factors in the CSF collected from 38 patients, 26 with PP-MS and 12 with SP-MS. Then, we performed a correlation matrix of all soluble factors expressed in the CSF. The CSF from patients with PP-MS and SP-MS had similar levels of cytokines and chemokines; however, the stratification of patients according to active or inactive magnetic resonance imaging (MRI) unveils some differences. Correlative studies between soluble factors in the CSF of patients with PP-MS and SP-MS revealed two clusters of immune mediators with pro-inflammatory functions, namely IFN-γ, MCP-1, MIP-1α, MIP-1β, IL-8, IP-10, and TNF-α (group 1), and anti-inflammatory functions, namely IL-9, IL-15, VEGF, and IL-1ra (group 2). However, most of the significant correlations between cytokines of group 1 and of group 2 were lost in patients with more severe disability (EDSS ≥ 4) compared to patients with mild to moderate disability (EDSS < 4). These results suggest a common regulation of cytokines and chemokines belonging to the same group and indicate that, in patients with more severe disability, the production of those factors is less coordinated, possibly due to advanced neurodegenerative mechanisms that interfere with the immune response.

【 授权许可】

Unknown