Pathophysiology of Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is arguably the best understood autoimmune disease, and its study has also led to fundamental appreciation of mechanisms of neuromuscular transmission. MG is caused by antibodies against the acetylcholine receptor (AChR), which produce a compromise in the end-plate potential, reducing the safety factor for effective synaptic transmission. It is clear that AChR antibody destruction of the postsynaptic surface is dependent on complement activation. A muscle-specific kinase has been recently found to be an antigenic target in MG patients without antibodies against the AChR. Autoantibody production in MG is a T-cell-dependent process, but how a breakdown in tolerance occurs is not known. In MG there is an interesting differential involvement of muscle groups, in particular, the extraocular muscles. This article reviews normal neuromuscular transmission, mechanisms of the autoimmune process of MG, and differential susceptibility of eye muscles to MG.

A Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models

“…These Abs activate complement at the neuromuscular endplate causing microlysis and reducing the number of AChR, thus hampering the correct transmission of impulses between motor neurons and muscle leading to weakness and fatigability (38)(39)(40). EGTA serum from an aHUS patient carrying the factor H C-terminal mutation W1183L.…”

Selection of a human butyrylcholinesterase-like antibody single-chain variable fragment resistant to AChE inhibitors from a phage library expressed inE. coli

“…In line with this notion, patients who develop myasthenia gravis have circulating 150 kDa autoantibodies that reach the neuromuscular junction, bind to the acetylcholine receptor, and block cholinergic transmission. [45][46][47] Finally, our experiments demonstrated that WZ1-14.2.1 may function in physiologic conditions (pH 7.4, 37 °C) we reproduced in the modified Ellmann assay. On the other hand, the mass/activity ratio (i.e., the specific activity of WZ1-14.2.1) is probably inappropriate for its clinical use, due to the need of administering the active principle in the order of grams/dose, been the abzyme more than one-thousand weaker in terms of k cat than acetylcholinesterase.…”

Investigation on life quality in patients with myasthenia gravis in Croatia

“…Miastenija gravis je autoimuna bolest o kojoj postoji najveći broj znanstveno citabilnih članaka [2,5], te služi kao model za izučavanje drugih autoimunih bolesti. Unatoč znatnom stupnju poznavanja patofiziologije [2,[5][6][7]10,11], pravi uzrok nastanka bolesti nije u cijelosti znanstveno verificiran.…”

“…Miastenija gravis je rijetka kronična, neuromuskularna i autoimuna bolest [1][2][3][4][5][6][7][8][9][10][11] …”

“…Miastenija gravis stečena je bolest, za koju postoji genetska sklonost u određenim skupinama opće populacije [obitelj, etničke skupine] [9,12,13,14]. Uzrok bolesti je poremećaj prijenosa podražaja sa živca na mišić u području neuromišićne spojnice [5,6,[9][10][11]. Prijenosnici podražaja [molekule neurotransmitera acetilkolina], i komponente neuromišićne spojnice [molekule proteoglikana agrina], nastaju u završetku živčanog vlakna odakle se oslobađaju, i zatim vežu na receptore na površini mišićnog vlakna.…”