Autoantibodies in different forms of myasthenia gravis and in the Lambert–Eaton syndrome

Abstract

In the Lambert–Eaton myasthenic syndrome (LEMS), the neuromuscular junction defect is presynaptic rather than postsynaptic, and it results in reduced quantal release of acetylcholine (ACh). This chapter concentrates on the serological studies that demonstrated the presence of antibodies in myasthenia gravis (MG) and LEMS, and their significance with respect to other clinical aspects of the two diseases. The acetylcholine receptor (AChR) is a pentameric membrane protein with two α-subunits and one each of the β, δ, and ɛ at the normal neuromuscular junction; and β, γ, and δ in extra-junctional regions of mature muscle or at the endplate in fetal muscle. Fetal AChR antibodies directly block fetal AChR function, and not adult AChR function. Seronegative MG (SNMG) is similar to AChR antibody positive MG in its clinical features, in electrophysiological defects, and in thymic pathology. The criteria that helped to define MG as an autoimmune disease also applied to the Lambert–Eaton myasthenic syndrome (LEMS). Voltage-gated calcium channels (VGCCs) are a family of channels composed of an α1 subunit that contains the calcium pore and determines the functional subtype and sensitivity to various neurotoxins. Using different neurotoxins that bind to different subtypes of VGCC, it was possible to demonstrate antibodies in patients with LEMS using the radioimmunoprecipitation technique.