The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis
Georgia Mandolesi,
Francesca Romana Rizzo,
Sara Balletta,
Mario Stampanoni Bassi,
Luana Gilio,
Livia Guadalupi,
Monica Nencini,
Alessandro Moscatelli,
Colleen Patricia Ryan,
Valerio Licursi,
Ettore Dolcetti,
Alessandra Musella,
Antonietta Gentile,
Diego Fresegna,
Silvia Bullitta,
Silvia Caioli,
Valentina Vanni,
Krizia Sanna,
Antonio Bruno,
Fabio Buttari,
Chiara Castelli,
Carlo Presutti,
Francesca De Santa,
Annamaria Finardi,
Roberto Furlan,
Diego Centonze,
Francesca De Vito
Affiliations
Georgia Mandolesi
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Francesca Romana Rizzo
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Sara Balletta
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Mario Stampanoni Bassi
Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy
Luana Gilio
Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy
Livia Guadalupi
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Monica Nencini
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Alessandro Moscatelli
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Colleen Patricia Ryan
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Valerio Licursi
Laboratory of Functional Genomics and Proteomics of Model Systems, Department of Biology and Biotechnologies “C. Darwin,” University of Rome “Sapienza”, Rome 00185, Italy
Ettore Dolcetti
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Alessandra Musella
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Antonietta Gentile
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Diego Fresegna
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Silvia Bullitta
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Silvia Caioli
Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy
Valentina Vanni
Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, 00166 Rome, Italy
Krizia Sanna
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Antonio Bruno
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Fabio Buttari
Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy
Chiara Castelli
Laboratory of Functional Genomics and Proteomics of Model Systems, Department of Biology and Biotechnologies “C. Darwin,” University of Rome “Sapienza”, Rome 00185, Italy
Carlo Presutti
Laboratory of Functional Genomics and Proteomics of Model Systems, Department of Biology and Biotechnologies “C. Darwin,” University of Rome “Sapienza”, Rome 00185, Italy
Francesca De Santa
Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), 00015 Rome, Italy
Annamaria Finardi
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy
Roberto Furlan
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy
Diego Centonze
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
Francesca De Vito
Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy
The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation. Additionally, we found that the CSF let-7b-5p levels were significantly reduced in patients with the progressive MS compared to patients with relapsing-remitting MS and were negatively correlated with characteristic hallmark processes of the two phases of the disease. Indeed, in the non-progressive phase, let-7b-5p inversely associated with both central and peripheral inflammation; whereas, in progressive MS, the CSF levels of let-7b-5p negatively correlated with clinical disability at disease onset and after a follow-up period. Overall, our results uncovered, by the means of a multidisciplinary approach and multiple statistical analyses, a new possible pleiotropic action of let-7b-5p in MS, with potential utility as a biomarker of MS course.