TY - JOUR
T1 - Etiology of myasthenia gravis
T2 - Innate immunity signature in pathological thymus
AU - Cavalcante, Paola
AU - Cufi, Perrine
AU - Mantegazza, Renato
AU - Berrih-Aknin, Sonia
AU - Bernasconi, Pia
AU - Le Panse, Rozen
PY - 2013/7
Y1 - 2013/7
N2 - Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction (NMJ), whose clinical hallmark is muscle weakness and early fatigability. The main target of autoimmunity in MG is the acetylcholine receptor (AChR) located in the NMJ. It is now widely accepted that the thymus is probably the prime site of autoimmunity development and maintenance in AChR-positive MG patients; however, the exact mechanisms triggering and perpetuating the intra-thymic autoimmune response to AChR are still unknown. As with many autoimmune diseases, MG has a multifactorial etiology, resulting from complex interactions between genetic and environmental factors, as fully described in this review. Among environmental factors, viral infections could play a central role in autoimmunity, mainly through the induction of dysregulated Toll-like receptor (TLR)-mediated innate immune responses, which can lead to inflammation and adaptive autoimmune response. Growing evidence of chronic inflammation, TLR activation, and persistent viral infections in the thymus of MG patients, strongly supports the hypothesis that, in the context of a genetic susceptible background, the intrathymic innate immune responses to pathogen infections might contribute to MG etiology.
AB - Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction (NMJ), whose clinical hallmark is muscle weakness and early fatigability. The main target of autoimmunity in MG is the acetylcholine receptor (AChR) located in the NMJ. It is now widely accepted that the thymus is probably the prime site of autoimmunity development and maintenance in AChR-positive MG patients; however, the exact mechanisms triggering and perpetuating the intra-thymic autoimmune response to AChR are still unknown. As with many autoimmune diseases, MG has a multifactorial etiology, resulting from complex interactions between genetic and environmental factors, as fully described in this review. Among environmental factors, viral infections could play a central role in autoimmunity, mainly through the induction of dysregulated Toll-like receptor (TLR)-mediated innate immune responses, which can lead to inflammation and adaptive autoimmune response. Growing evidence of chronic inflammation, TLR activation, and persistent viral infections in the thymus of MG patients, strongly supports the hypothesis that, in the context of a genetic susceptible background, the intrathymic innate immune responses to pathogen infections might contribute to MG etiology.
KW - Etiology
KW - Inflammation
KW - Myasthenia gravis
KW - Thymus
KW - Toll-like receptors
KW - Viral infection
UR - http://www.scopus.com/inward/record.url?scp=84879167018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879167018&partnerID=8YFLogxK
U2 - 10.1016/j.autrev.2013.03.010
DO - 10.1016/j.autrev.2013.03.010
M3 - Article
C2 - 23535157
AN - SCOPUS:84879167018
VL - 12
SP - 863
EP - 874
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
SN - 1568-9972
IS - 9
ER -