Insights into the pathogenesis of multiple sclerosis: genetics and environment

Abstract

It has been a great honor to host the second MS Summer College in Sapporo. For the past 13 years, clinicians and researchers involved in multiple sclerosis (MS) research have gathered to present their most recent findings and to engage in enthusiastic and informative discussions. Last year, the meeting was reconceived as the first MS Summer College, organized by Professor Kira, and building on the success of that first meeting, it is my great pleasure to welcome everyone to the second MS Summer College. I have confidence that we will continue to advance MS research while deepening our friendship at the same time. The theme of this second MS Summer College was “Insights into the pathogeneses of MS: genetics and environment.” The development of MS is influenced by interactions between multiple genetic and environmental factors. Historically, epidemiological studies have provided clues for the triggers of MS. These studies have identified latitude, or vitamin D as an important risk factor for MS. In addition, the observed link between infectious agents such as Epstein–Barr (EB) virus and MS has led to the “hygiene hypothesis” of MS development, which is further supported by recent advances in the field of mucosal immunology. At this meeting, Professor Goodin gave us an overview of the epidemiology of MS. In the following sessions, Professor Ohno and Dr. Okuno presented their current research on immune regulation by gut microflora, and Professor Fujiwara described recent progress made in the field of autoimmunity triggered by EB virus. In addition to epidemiological and immunological approaches, genetic studies using advanced technologies have identified several human leukocyte antigen (HLA) and non-HLA susceptibility loci involved in MS development. Continued advances in MS genetics lead to the elucidation of MS etiology and further aided in drug discovery and development. Professor Matsushita gave a comprehensive review of recent advances and perspectives in genetic studies on MS. As the effects of individual genes or even combinations of genes on MS development are relatively minor, they explain, at most, only half of the genetic risks for developing MS. Therefore, the limitations of these genetic studies based on “common disease–common variant hypothesis” have been pointed out. In this context, epigenetic mechanisms have been suggested as underlying MS pathogenesis and may partly explain the “missing heritability” of this complex disease. To discuss this in detail, Professor Iwamoto, following an overview of epigenetic studies on MS presented by Dr. Miyazaki, described the recent progress made in the epigenetics of psychiatric disorders, which is expected to provide insights into future research in MS epigenetics. We were also pleased to host Professor Nakashima, who gave a special clinical lecture on the recently identified anti-myelin oligodendrocyte glycoprotein (MOG) antibody-related disease, which has recently been identified among anti-AQP4 antibody-negative neuromyelitis optica and other demyelinating disorders. All these exciting and informative lectures were held in Sapporo, a young and vibrant city surrounded by beautiful nature and with abundant fresh food. I am firmly convinced that this issue of Clinical and Experimental Neuroimmunology (Supplemental Vol. 6) will provide you with the most recent progress in MS research and convey the stimulating atmosphere of the second MS Summer College. The author has no financial interests in the publication of the contents of this article or has no relationships with any company with such financial interests.