Over the last 20 years, there has been an explosion of antibodies to glial antigens and synaptic proteins, mostly neurotransmitter receptors or associated neuronal proteins. But the field really developed when, in the 1970s, the first reports of acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG) appeared; the antibodies bind to extracellular epitopes on the AChR, the patients improve substantially when the antibodies are reduced by immunotherapies, and one can transfer disease to mice by injection of the patient purified serum IgG. One intriguing, although rare, aspect of MG is that AChR antibodies during gestation, not always associated with clinical myasthenia in the mother or transient myasthenia in the baby, can be associated with a persistent myopathic condition in the child.

Following the discovery of AChR antibodies, the family of peripheral neuropathies with antibodies to myelin associated glycoprotein (MAG), and more frequently gangliosides were studied. Now some of the peripheral diseases are called nodopathies because they have antibodies to extracellular epitopes of nodal proteins like CASPR1, contactin 1 and neurofascin 155/186. There are also rare autoimmune autonomic disorders associated with antibodies to a neuronal ganglionic form of the AChR.

Neuromyelitis optica (NMO) is a neuroinflammatory disease affecting optic nerve, spinal cord and often brainstem. The group of the Mayo Clinic, led by Vanda Lennon, was the first to show in 2004/5 that there were antibodies to the water channel, AQP4, in NMO, and this discovery led to an explosion of papers on NMO, related diseases such as myelin oligodendrocyte glycoprotein (MOG), and their clinical, serological and imaging associations.

The autoimmune forms of encephalitis are the other main group of antibody-mediated conditions. Antibodies to NMDA, GABA and AMPA receptors, proteins LGI1/CASPR2 and DPPX that are associated with Kv1 and Kv4.3 potassium channels respectively, are now regularly found in patients with various forms of limbic encephalitis and the most common condition, NMDAR-Ab encephalitis. The latter presents with seizures, psychiatric or behavioural disorders and, if not treated promptly, can progress to a complex movement disorder, autonomic instability and loss of consciousness. A rare condition is the stiff-person syndrome associated with glycine receptor antibodies. Each of these disorders responds to immunotherapies, but the course of improvement can be very different and the final state usually involves some disability.

The aim of the lecture will be to provide a personal overview of these clinically-important disorders and draw attention to the many aspects that require a better understanding of their neuroimmunological basis.