What is seronegative myasthenia gravis (MG)?

Updated: Aug 27, 2018
  • Author: Abbas Jowkar, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

Patients without anti-AChR antibodies are recognized as having seronegative MG (SNMG). These patients usually have autoantibodies (IgG4) against muscle-specific kinase (MuSK). These do not activate complement, unlike AChR-abs. MuSK plays a critical role in postsynaptic differentiation and clustering of AChRs at the NMJ to promote efficient neuromuscular transmission. MuSK autoantibodies are pathogenic and this is proven by passive transfer and active immunization studies in animals. It is likely MuSK autoantibodies disrupt the interaction between MuSK and the LRP4 and collagen Q. Patients with anti-MuSK antibodies are predominantly women, with a tendency of disease onset in the third or fourth decades. They have prominent oculobulbar weakness with dysarthria. Face and tongue atrophies have been reported in long-standing disease. It is often confused with bulbar amyotrophic lateral sclerosis (ALS). Another group has reported patients who exhibit prominent neck (dropped head syndrome), shoulder, and respiratory weakness. [12, 13]  Myasthenic crises appear to be more frequent in patients with MuSK antibodies. [22, 23]

The role of the thymus in the pathogenesis of MG is not entirely clear, but 75% of patients with MG have some degree of thymus abnormality (eg, hyperplasia or thymoma). Histopathologic studies have shown prominent germinal centers. Epithelial myoid cells normally present in the thymus resemble skeletal muscle cells and possess AChRs on their surface membrane. These cells may become antigenic by molecular mimicry and unleash an autoimmune attack on the muscular endplate nicotinic AChRs.


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