Neurologic autoimmunity: mechanisms revealed by animal models

Over the last decade, neurologic autoimmunity has become a major consideration in the diagnosis and management of patients with many neurologic presentations. The nature of the associated antibodies and their targets has led to appreciation of the importance of the accessibility of the target antigen to antibodies, and a partial understanding of the different mechanisms that can follow antibody binding. This chapter will first describe the basic principles of autoimmune inflammation and tissue damage in the central and peripheral nervous system, and will then demonstrate what has been learnt about neurologic autoimmunity from circumstantial clinical evidence and from passive, active, and occasionally spontaneous or genetic animal models. It will cover neurologic autoimmune diseases ranging from disorders of neuromuscular transmission, peripheral and ganglionic neuropathy, to diseases of the central nervous system, where autoantibodies are either pathogenic and cause destruction or changes in function of their targets, where they are harmless bystanders of T-cell-mediated tissue damage, or are not involved at all. Finally, this chapter will summarize the relevance of current animal models for studying the different neurologic autoimmune diseases, and it will identify aspects where future animal models need to be improved to better reflect the disease reality experienced by affected patients, e.g., the chronicity or the relapsing/remitting nature of their disease.