Advances In The Immunopathogenesis Of Multiple Sclerosis

P.A. MURARO, A. LUGARESI, D. GAMBI Many of the pathological aspects of multiple sclerosis (MS) lesions have been known for over a century. It is only recently, however, that different patterns of demyelination have been linked to distinct pathways of immune-mediated tissue destruction. In particular, the inter-individual heterogeneity of MS lesions has suggested that different mechanisms may act in different patients, accounting for the variability observed in clinical course, immunological findings in peripheral blood and cere brospinal fluid (CSF), and response to immunomodulatory treatments. To provide an overview of the basic mechanisms possibly involved in MS lesion initiation and development, an international meeting was organized in the context of the annual Congress of the Italian Neuroimmunology Association (AINI), held at the University of Chieti, in Chieti Italy on 29 October 1998. The high standard of presentations prompted us to report them in extended form, to highlight recent pro gress in the understanding of basic mechanisms sustaining MS immuno pathogenesis. A central role in the possible mechanisms leading to myelin destruc tion has been attributed to T lymphocytes reactive to myelin antigens. Studies on the myelin antigen-specific T cell repertoire have contributed significant advances to our knowledge of autoimmunity (Chapters 1,2).

Over the past decade, we have made great advances in the field of multiple sclerosis (MS) research, and this book focuses on those advances in MS pathogenesis and treatment. While some of these advances have been through new approaches and ideas that have emerged in the last decade such as the newly identified protective role that amyloid proteins may play in MS or the use of helminths to treat autoimmune diseases, others have evolved from previous theories and ideas that have only now gained momentum and a deeper understanding such as the role of HLA or gender in MS susceptibility. This book covers these emerging and evolving topics and highlights the substantial advancements made in elucidation of the factors regulating susceptibility or disease progression, identification of new ways to monitor or predict MS pathology, and development of new strategies for treating MS.

Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known, but it is generally accepted that it is autoimmune in nature. Our knowledge of the pathogenesis of MS has increased tremendously in the past decade through clinical studies and the use of experimental autoimmune encephalomyelitis (EAE), a model that has been widely used for MS research. Major advances in the field, such as understanding the roles of pathogenic Th17 cells, myeloid cells, and B cells in MS/EAE, as well as cytokine and chemokine signaling that controls neuroinflammation, have led to the development of potential and clinically approved disease-modifying agents (DMAs). There are many aspects related to the initiation, relapse and remission, and progression of MS that are yet to be elucidated. For instance, what are the genetic and environmental risk factors that promote the initiation of MS, and how do these factors impact the immune system? What factors drive the progression of MS, and what are the roles of peripheral immune cells in disease progression? How do the CNS-infiltrated immune cells interact with the CNS-resident glial cells when the disease progresses? What is the role of microbiome in MS? Can we develop animal models that better represent subcategories of MS? Understanding the cellular and molecular mechanisms that govern the pathogenesis of MS will help to develop novel and more specific therapeutic strategies that will ultimately improve clinical outcomes of the treatments. This Special Issue of Cells has published original research articles, a retrospective clinical report, and review articles that investigate the cellular and molecular basis of MS.

Over the past decade, we have made great advances in the field of multiple sclerosis (MS) research, and this book focuses on those advances in MS pathogenesis and treatment. While some of these advances have been through new approaches and ideas that have emerged in the last decade such as the newly identified protective role that amyloid proteins may play in MS or the use of helminths to treat autoimmune diseases, others have evolved from previous theories and ideas that have only now gained momentum and a deeper understanding such as the role of HLA or gender in MS susceptibility. This book covers these emerging and evolving topics and highlights the substantial advancements made in elucidation of the factors regulating susceptibility or disease progression, identification of new ways to monitor or predict MS pathology, and development of new strategies for treating MS.

Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Consequently, the current strategies for treatment and management of patients are limited in their efficacy. The mechanisms of tissue protection and repair are probably even less understood. One reason for these limitations is the enormous complexity of the disease and every facet of its pathogenesis, the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy of treatments and their side effects. The aim of this book is to review the most recent advances made in this highly complex field.

Controversy still exists regarding how early disease-modifying agents (DMA) should be commenced and whether all patients with relapsing-remitting MS should in fact be treated. To answer these questions, it is also important to know the natural history of the disease. MS affects nearly 400,000 people in the United States. With their novel, multifaceted approach to basic science, the authors of this book offer help to clinicians and hope to patients.

Designing immunotherapeutics, drugs, and anti-inflammatory reagents has been at the forefront of autoimmune research, in particular multiple sclerosis, for over 20 years. Delivery methods that are used to modulate effective and long-lasting immune responses have been the major focus. This Special Issue focused on delivery methods to be used for vaccines, immunotherapeutic approaches, drug design, and anti-inflammatories and their outcomes in preclinical studies and clinical trials.

Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known, but it is generally accepted that it is autoimmune in nature. Our knowledge of the pathogenesis of MS has increased tremendously in the past decade through clinical studies and the use of experimental autoimmune encephalomyelitis (EAE), a model that has been widely used for MS research. Major advances in the field, such as understanding the roles of pathogenic Th17 cells, myeloid cells, and B cells in MS/EAE, as well as cytokine and chemokine signaling that controls neuroinflammation, have led to the development of potential and clinically approved disease-modifying agents (DMAs). There are many aspects related to the initiation, relapse and remission, and progression of MS that are yet to be elucidated. For instance, what are the genetic and environmental risk factors that promote the initiation of MS, and how do these factors impact the immune system? What factors drive the progression of MS, and what are the roles of peripheral immune cells in disease progression? How do the CNS-infiltrated immune cells interact with the CNS-resident glial cells when the disease progresses? What is the role of microbiome in MS? Can we develop animal models that better represent subcategories of MS? Understanding the cellular and molecular mechanisms that govern the pathogenesis of MS will help to develop novel and more specific therapeutic strategies that will ultimately improve clinical outcomes of the treatments. This Special Issue of Cells has published original research articles, a retrospective clinical report, and review articles that investigate the cellular and molecular basis of MS.