Welcome Letter
Dear Students,
Erdem Tuzun and I are delighted to take you through the autoimmune disorders of the neuromuscular junction (NMJ), and as you will see, we will even venture into the central nervous system.
Since the NMJ is the archetypal synapse, and the diseases that affect it are prototypical antibody-mediated conditions, we discuss them at some length. However, this first requires that you know something about neuromuscular transmission and its key components, as these are the targets for of autoimmune attack. This, in turn, requires a brief review of immunology. With this foundation, we can begin a discussion of the diseases of the NMJ, most importantly, myasthenia gravis, but also seronegative myasthenia, Lambert Eaton myasthenic syndrome, and acquired neuromyotonia. You will then see how, using our knowledge of a very rare disease that affects the periphery and the central nervous system (Morvan’s syndrome), we and others have been able to more broadly explore antibody-mediated diseases of the CNS. The text covers these diseases systematically and the references encompass the most general aspects, but there is ample opportunity for further explorfation of the literature.
What we hope you will appreciate, more than anything, from this module is the history of the research on NMJ disease and how experimental and basic science have combined to provide an understanding of these conditions; the extent to which the identification of specific target antigens has revolutionized our understanding of them and thus of their diagnosis and treatment; and how research into NMJ disease has helped us in identifying other, unrecognized or neglected, immunotherapy-responsive conditions of the CNS.
My contribution to this module consists of the clinical immunology aspects while Dr Tüzün covers most of the clinical questions and the more detailed immunology, particularly of the experimental model of myasthenia. We hope you enjoy this module and interacting with us.

Angela Vincent
Professor of Neuroimmunology,
Honorary Consultant in Immunology,
University of Oxford

Erdem Tüzün
Consultant Neuroimmunologist,
University of Istanbul, Turkey.

Abstract: Neuromuscular transmission was the original model for studying synaptic transmission in the nervous system largely because of the easy accessibility of the neuromuscular junction. There are genetic, neurotoxic, and autoimmune diseases of the neuromuscular junction. Genetic diseases are rare and caused by mutations in many of the key molecules involved in transmission. Neurotoxicity occurs due to poisoning by venomous species and also by botulinism, which is still clinically important in some parts of the world. Autoimmunity, the main topic of this Unit, occurs when autoantibodies bind to specific targets at the neuromuscular junction, which leads to defective transmission. Here, we first briefly describe the structure and function of the neuromuscular junction, and then discuss the clinical, pathological, and immunological features of four autoimmune disorders of neuromuscular transmission: myasthenia gravis, myasthenia gravis with MuSK antibodies, the Lambert Eaton myasthenic syndrome, and acquired neuromyotonia. Each of these conditions is caused by autoantibodies to a receptor or ion channel.
These diseases will be discussed in detail and provide the paradigms for understanding the newly described CNS disorders that are briefly reviewed at the end of the Unit. Collectively, many of these conditions can now be called 'autoimmune channelopathies.'

Development of the Unit
This Unit consists of four parts. The first consists of the anatomy, physiology, and biochemistry of neuromuscular transmission, about a brief presentation of the molecules that are targets for the autoimmune diseases under discussion, and a simple overview of how antibodies are produced. The second, largest section discusses in some detail myasthenia gravis, which is the main autoimmune disorder of neuromuscular transmission, as well as its pathology and etiology; it also offers a few comments on the different treatments. In the third section, we briefly describe the other two autoimmune disorders, Lambert Eaton myasthenic syndrome and acquired neuromyotonia. In the fourth, we take note of the newly described diseases of the central nervous system, which, due to the characteristic presence of antibodies directed against ion channels and receptors, are proving to be immunotherapy responsive.