Characteristics of myasthenia gravis with antibodies to muscle‐specific kinase and low‐density lipoprotein‐related receptor protein 4

Abstract

Myasthenia gravis (MG) is characterized by fatigable weakness of voluntary muscles caused by immunoglobulin G autoantibodies binding to post‐synaptic proteins at the neuromuscular junction. Antibodies specific for the acetylcholine receptor are detected in the great majority (85%) of MG patients. Serum immunoglobulin G binding to the muscle‐specific kinase (MuSK) are found in approximately 40% of anti‐acetylcholine receptor‐negative patients. Recently, the low‐density lipoprotein receptor‐related protein 4 (Lrp4), which is the MuSK co‐receptor for agrin, has been recognized as a new antigen in MG. Specific antibodies bind to the extracellular domains of MuSK and Lrp4 and, as experimental models have shown, interfere with the protein function. The present review describes the MuSK‐Lrp4 complex, and summarizes the effects of MuSK and Lrp4 antibodies at the neuromuscular junction. Furthermore, the epidemiological and clinical characteristics, the response to therapy and the controversies in management of the specific diseases are discussed.

Oral corticosteroid therapy and present disease status in myasthenia gravis

“…Evoli and Iorio described the muscle-specific receptor tyrosine kinase and low-density lipoprotein receptorrelated protein 4 complex, in neuromuscular junctions and also the clinical characteristics of MG with autoantibodies to these specific molecules. 6 It is important to understand these distinctive features to carry out accurate diagnoses.…”

Coexistence of myasthenia gravis and Lambert–Eaton myasthenic syndrome in a small cell lung cancer patient

“…[ 8 ] AChR antibodies are present in 50% of patients with ocular MG and 85% of patients with generalized MG. [ 8 ] MuSK antibodies are found in approximately 40% (range of 0–70%) of the 15% AChR-negative generalized MG group but are rarely positive in patients with ocular MG. [ 5 ] More recently, LRP4 antibodies have been found in a small number of patients who are negative for AChR and MuSK. [ 9 ] Autoantibodies to agrin are thought another autoantigen in patients with MG and may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the neuromuscular junction. [ 10 ] However, as known, the antigenic target in LEMS is the P/Q type voltage-gated calcium channel (VGCC) on the presynaptic nerve terminal.…”

Significance of follow‐up thoracic imaging in myasthenia gravis

“…However, in anti-muscle-specific receptor tyrosine kinase antibody-positive MG, thymic abnormalities are very rare. 4 The incidence of thymoma in patients with MG has been reported as 22.7% in a previous Japanese study. 5 Therefore, it is considered mandatory for patients to undergo a thoracic imaging study, such as computed tomography (CT) or magnetic resonance imaging, on diagnosis of MG, and one is carried out almost without exception.…”

“…Patients with thymoma‐associated MG are usually anti‐AChR antibody‐positive, with rare exceptions. However, in anti‐muscle‐specific receptor tyrosine kinase antibody‐positive MG, thymic abnormalities are very rare . The incidence of thymoma in patients with MG has been reported as 22.7% in a previous Japanese study .…”