Extraocular muscle susceptibility to myasthenia gravis: unique immunological environment?
Extraocular muscle (EOM) is susceptible to neuromuscular junction disorders, in particular, myasthenia gravis (MG). While EOM physiological characteristics and the ocular motor system requirements contribute to the propensity of ocular motor deficits observed among patients with MG, the authors propose that EOM have immunological features that place the muscles at risk for immune attack. Genomic profiling studies have demonstrated that genes associated with the immune response are differentially expressed in EOM, with particular differences in both classical and alternative complement-mediated immune response pathways. Intrinsic complement regulators are expressed at lower levels at rodent EOM neuromuscular junctions, which would put them at risk for the complement-mediated injury that occurs in MG. In fact, systemic C inhibition in experimental autoimmune MG (EAMG) induced by administration of acetylcholine receptor (AChR) antibodies or immunization with AChR will eliminate complement deposition at junctions of other skeletal muscle, but not EOM. Also, EOM junctions have greater injury in active and passive EAMG by several measures, suggesting that the lack of complement inhibition puts the EOM at risk. Among ocular myasthenia patients, serum AChR antibody levels are low, which would support the concept that EOM junctions are more susceptible to antibody injury than are other junctions. These observations suggest that complement inhibitory therapies may prove to be particularly effective in treatment of ocular myasthenia.
Soltys
Jindrich
J
Department of Neurology & Psychiatry, Saint Louis University, 1438 South Grand Avenue, St. Louis, MO 63104, USA.
Gong
Bendi
B
Kaminski
Henry J
HJ
Zhou
Yuefang
Y
Kusner
Linda L
LL
D000818:Animals; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology / Q000473:pathology; D006801:Humans; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009801:Oculomotor Muscles / Q000033:anatomy & histology / Q000276:immunology*
D003165:Complement System Proteins