AUTHOR=Weissert Robert TITLE=Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00336 DOI=10.3389/fimmu.2017.00336 ISSN=1664-3224 ABSTRACT=

There are common aspects and mechanisms between different types of autoimmune diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), and autoimmune encephalitis (AE) as well as paraneoplastic inflammatory disorders of the central nervous system. To our present knowledge, depending on the disease, T and B cells as well as antibodies contribute to various aspects of the pathogenesis. Possibly the events leading to the breaking of tolerance between the different diseases are of great similarity and so far, only partially understood. Beside endogenous factors (genetics, genomics, epigenetics, malignancy) also exogenous factors (vitamin D, sun light exposure, smoking, gut microbiome, viral infections) contribute to susceptibility in such diseases. What differs between these disorders are the target molecules of the immune attack. For T cells, these target molecules are presented on major histocompatibility complex (MHC) molecules as MHC-bound ligands. B cells have an important role by amplifying the immune response of T cells by capturing antigen with their surface immunoglobulin and presenting it to T cells. Antibodies secreted by plasma cells that have differentiated from B cells are highly structure specific and can have important effector functions leading to functional impairment or/and lesion evolvement. In MS, the target molecules are mainly myelin- and neuron/axon-derived proteins; in NMOSD, mainly aquaporin-4 expressed on astrocytes; and in AE, various proteins that are expressed by neurons and axons.