Neuroimmunology of Multiple Sclerosis: Exploring New Perspectives
Ass. Professor of Neurology Maria Anagnostouli E-Mail
Multiple Sclerosia and Demyelinating Diseases Unit,1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Athens, Greece
Prof. Ilias Doxiadis E-Mail
Institute for Transfusion Medicine, University Hospital Leipzig Leipzig, Germany
Multiple Sclerosis (MS) is a chronic autoimmune disease with a neuroinflammatory and neurodegenerative component that affects both adults and children, as a rare clinical situation, the latest.
The main genetic risk to MS initiation for Caucasians is considered the HLA-DRB1:15:01 allele, worldwide, while other HLA alleles are connected to eastern-MS type and Neuromyelitis Optica (NMO), Neuromyelitis Spectrum Disorders (NMOSD), Acute Disseminating Encephalomyelitis (ADEM) or other demyelinating diseases. HLA-DRB1*15:01 allele has been associated with age at onset, gender, clinical manifestation, clinical course, Magnetic Resonance Imaging (MRI) findings, cognitive status, Oligoclonal Bands (OCBs) presence, neutralizing antibodies production and mainly response to treatment. At the neuroimmunological frame per se, immunogenetic profile affects initial and ongoing innate and adaptive immune responses and importantly microbiome and immune response at the gut level, with impact to Blood Brain Barrier (BBB) integrity, with disruption and T and B cell invasion in the Central Nervous System (CNS).
Multiple Sclerosis was classically considered a T cell mediated disorder, while the last decade the crucial role of B cells in MS immunopathophysiology emerged in a therapeutically useful way, since many monoclonal antibodies discovered, as B-cell targeted therapies. Additionally, new neuroimmunological achievements in MS paved the way to new perspectives of MS immuunopathophysiology and brought to our therapeutic armamendarium many new therapeutic agents and others that are under investigation in clinical trials, like BTKis, that target both adaptive and mainly innate immunity cells in CNS and go beyond neuroinflammation component.
New insights in brain lymphatics, connectome, exosomes, Epstein Barr Virus (EBV) connection with MS, Hematopoietic Stem Cell Transplantation (HSCT) and others have broadened our understanding in MS neuroimmunology.
Biomarkers in Clinically Isolated Syndrome (CIS) and early MS is an unmet need and neuroimmunologists and neurologists look forward a machine learning solution that will combine already existed biomarkers (HLA alleles, neurofilaments, cytokines, T and B cells subtypes, MRI findings, etc) in a really effective way towards an early and effective personalized therapeutic intervention, controlling disease progression.
Keywords: Multiple Sclerosis, neuroimmunology, HLA, T cells, B cells, cytokines, biomarkers, therapeutics, precision medicine immunotherapies, artificial intelligence