**Background of MUSK Antibodies**
MuSK (muscle-specific tyrosine kinase) antibodies are autoantibodies associated with a subset of myasthenia gravis (MG), a chronic autoimmune neuromuscular disorder. MuSK is a receptor tyrosine kinase critical for neuromuscular junction (NMJ) development and maintenance, facilitating acetylcholine receptor (AChR) clustering and synaptic signaling.
In MG, autoantibodies disrupt NMJ function, leading to muscle weakness. While most MG patients have antibodies against AChR, ~40% of AChR-negative cases exhibit MuSK antibodies (MuSK-MG). These IgG4 antibodies directly interfere with MuSK signaling, impairing AChR organization and reducing synaptic transmission efficiency.
MuSK-MG has distinct clinical features compared to AChR-MG, often presenting with prominent facial, bulbar, and respiratory muscle weakness, sparing limb muscles in early stages. Diagnosis relies on detecting MuSK antibodies via cell-based assays or radioimmunoprecipitation, as standard ELISA tests may fail due to conformational epitope specificity.
Treatment differs from conventional MG: acetylcholinesterase inhibitors (e.g., pyridostigmine) are less effective, while immunosuppressants, rituximab, or complement inhibitors (e.g., eculizumab) show better outcomes. Research continues to unravel MuSK’s role in autoimmunity and refine targeted therapies.
Understanding MuSK antibodies has advanced MG subtyping, emphasizing personalized approaches for this rare but severe autoimmune variant.