Immunopathology of acetylcholine receptors in myasthenia gravis

Abstract

It is now clear that the muscular weakness and fatigability seen in MG result from an antibody-mediated immune response to AChR. The mechanisms by which antibodies impair transmission are moderately well understood and detection of antibodies in patient's sera is a reliable diagnostic test for the disease. The spectrum of antibody specificities produced in MG is also beginning to be understood, largely through the use of antibodies produced in the experimental model EAMG. Treatment for MG continues to rely heavily on the symptomatic relief afforded by acetylcholinesterase inhibitors. However, the recent recognition of the autoimmune nature of MG has led to increased emphasis on immunosuppression and antibody removal with some beneficial effects. Despite all that has been learned, the level of ignorance has just been pushed back one step--from the neuromuscular junction to the immune system. What initiates the immune response to AChR in MG and how to specifically suppress this aberrant response remain completely unknown.

BMSCs-derived exosome miR-29a-3p improved the stability of rat myasthenia gravis by regulating Treg/Th17 cells

“…This leads to damage of AChR and associated proteins in the postsynaptic membrane, thereby affecting the interaction between the neurotransmitter acetylcholine (ACh) and the postsynaptic membrane, ultimately causing muscle weakness in patients with MG (Lindstrom, 2000). ACh is hydrolyzed by acetylcholinesterase (AChE) into smaller components that are reuptaken by synaptic terminals and subsequently resynthesized as Ach (Lindstrom, 2000;Seybold and Lindstrom, 1982). Therefore, clinical detection of AChE activity holds signi cant implications for MG patients (Heldal et al, 2014).…”

Repertoires of autoantibodies against homologous eye muscle in ocular and generalized myasthenia gravis differ

“…However, this does not appear to be caused exclusively by autoantibodies against AChR [16,22,23,25]. Recent experiments suggest that certain morphological (thymus) and immunological features in myasthenic patients are strongly related to the patients' anti-receptor antibody status [27], and immunoglobulin heavy-chain gene associations also indicate heterogeneity in myasthenia gravis [6].…”