Targets of the humoral autoimmune response in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS) with heterogeneous clinical, genetic and pathophysiological characteristics. The establishment of reliable biomarkers for diagnosis, prognosis and treatment of MS has therefore proven to be very difficult. During the last decades, mounting evidence has been collected for the involvement of B cells and antibodies in MS pathogenesis. A wide variety of autoantibodies has been described in MS and these autoantibodies could be useful biomarkers for MS. Since demyelination is a key component of MS pathogenesis, myelin antigens were first investigated as primary targets of autoantibodies in MS. More recently, it became evident that the humoral autoimmune response is not restricted to myelin but is much more widespread throughout the brain. Autoantibodies are formed against different CNS cell types, including neurons, oligodendrocytes and astrocytes, and even immune cells, indicating the complex heterogeneity of the disease. In this review, we give an extensive overview of the known autoantibody targets in MS, not according to the traditional subdivision of myelin and non-myelin components but according to each of the affected cell types, including the most recently described target antigens.