Article Sections

Introduction

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction characterized by fluctuating muscle weakness and fatigability.

Pathophysiology

MG is caused by an autoantibody-mediated, T cell–dependent attack on the postsynaptic nicotinic acetylcholine receptors (AChRs) of the neuromuscular junction ( Figure 1).  Blockade of the active site of AChRs prevents acetylcholine from binding and also triggers endocytosis of AChRs (receptor internalization), as well as complement-mediated membrane damage.  Over time, these changes result in reduced numbers of AChRs.  The decrease in available cation channels reduces the end plate potential following acetylcholine release ( Figure 2).  Because the threshold potential is not reached, the muscle cells do not depolarize as frequently, leading to defective neuromuscular transmission.

The thymus is involved in the differentiation of T cells and seems to be the site of autoimmunization in MG, perhaps by reacting to muscle-like cells in the thymus that express AChR antibodies.  This may be why most patients with MG are found to have some form of thymic disease (thymic hyperplasia, thymoma).

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