The auto-antigen repertoire in myasthenia gravis

Abstract

Myasthenia Gravis (MG) is an antibody-mediated autoimmune disorder affecting the postsynaptic membrane of the neuromuscular junction (NMJ). MG is characterized by an impaired signal transmission between the motor neuron and the skeletal muscle cell, caused by auto-antibodies directed against NMJ proteins. The auto-antibodies target the nicotinic acetylcholine receptor (nAChR) in about 90% of MG patients. In approximately 5% of MG patients, the muscle specific kinase (MuSK) is the auto-antigen. In the remaining 5% of MG patients, however, antibodies against the nAChR or MuSK are not detectable (idiopathic MG, iMG). Although only the anti-nAChR and anti-MuSK auto-antibodies have been demonstrated to be pathogenic, several other antibodies recognizing self-antigens can also be found in MG patients. Various auto-antibodies associated with thymic abnormalities have been reported, as well as many non-MG-specific auto-antibodies. However, their contribution to the cause, pathology and severity of the disease is still poorly understood. Here, we comprehensively review the reported auto-antibodies in MG patients and discuss their role in the pathology of this autoimmune disease.

Myasthenia gravis and amyotrophic lateral sclerosis: A pathogenic overlap

“…The co-occurrence of other autoimmune diseases and autoantibodies in MG patients may be explained by a general dysfunction of immune regulation [36]. Our patients had clinical and electrophysiological signs of ALS together with positive AChR antibodies at the primary examination, suggesting a co-appearance of pathognomonic processes for both diseases.…”

Myasthenogenicity of the main immunogenic region and endogenous muscle nicotinic acetylcholine receptors

“…Myasthenia gravis is caused by antibodies to muscle AChRs [1–3], but is associated with the presence of autoantibodies to many other proteins [22]. These other autoantibodies may reflect a genetic proclivity for antoimmune responses in MG patients, and may in some cases modify the impaired neuromuscular transmission in MG which results from loss of AChRs and disruption of the postsynaptic membrane.…”

An introduction to biomaterial-based strategies for curbing autoimmunity

“…18 In Grave's disease, the scenario is slightly different, thyroid-stimulating immunoglobulins recognize and bind to the thyrotropin receptor (TSH receptor) which stimulates the secretion of thyroxine and triiodothyronine. The result is high levels of circulating thyroid hormones and hyperthyroidism.…”