Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder of the neuromuscular junction. Approximately 20% of patients with generalized MG are “seronegative (herein, negative for antibodies against nicotinic acethylcholine receptor).” Seronegative MG patients have less benefit from thymectomy as compared with AchR-positive patients. Why could this happen?
Hy, I thinking that patients MG may have another pathogenesis of disease. You need exam other antibodies : like Anti-MuSK, titin and ryanodine antibodies who is correlates with MG severity.
Seronegative MG positive for anti-MuSK antinody tends to exhibit the better response to plasma exchange as compared with general anti-AchR Abs-positive patients.
Yes, but patients with anti-MuSK antibody's more efective response when treated with imunosuppresants.
Unfortunately I have no the clear explanation of the link between biochemical or biophysical mechanism MG, causing an antibody-mediiated autoimmune disorder of neuromuscular function, and biochemical or biophysical mechanism of thymus operation.
MuSK antibodies are largely belong to IgG4. This is related to the better therapeutic response to immuno-suppressive therapies?
Seronegative myasthenia gravis (MG) patients with antibodies against muscle-specific tyrosine kinase (MuSK Abs) frequently exhibit oculobulbar, neck, or respiratory weakness and are less likely to benefit from thymectomy as compared with acetylcholine receptor (AchR)-positive MG.(1,2) Notably, seronegative MG patients significantly respond to plasma exchange even at MG crisis.(1,3,4) MuSK is expressed at the neurotransmitter junction. However, the postsynaptic membrane tends to be preserved in the motor end-plate of seronegative MG patients, because MuSK Abs are largely IgG4, a subclass which does not strongly activate complement C3.(4,5) Thus, attenuated Agrin/LRP4-MuSK axis is expected to be responsible for the clinical involvement of the impaired muscles in MuSK Abs-associated MG and the better therapeutic response to immunotherapies.
References
1. Sanders DB, El-Salem K, Massey JM, McConville J, Vincent A. Clinical aspects of MuSK antibody positive seronegative MG. Neurology 2003;60:1978-80.
2. Evoli A, Tonali PA, Padua L, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 2003;126:2304-11.
3. Suzuki H, Motomura M, Yoshimura T, et al. [A case of myasthenia gravis with anti-MuSK antibodies showing a dramatic improvement with plasma exchange]. Rinsho Shinkeigaku 2005;45:510-3.
4. Shiraishi H, Motomura M, Yoshimura T, et al. Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis. Ann Neurol 2005;57:289-93.
5. Tuzun E, Christadoss P. Complement associated pathogenic mechanisms in myasthenia gravis. Autoimmun Rev 2013;12:904-11.
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biomolecules
- Nucleic Acids
- RNA
- Small RNA
- microRNA