title: Etiology of myasthenia gravis: innate immunity signature in pathological thymus.
abstract: 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.
authors.affiliation: Department of Neurology IV, Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico 'Carlo Besta', Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cavalcante
authors.forename: Perrine
authors.initials: P
authors.lastname: Cufi
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.forename: Sonia
authors.initials: S
authors.lastname: Berrih-Aknin
authors.forename: Pia
authors.initials: P
authors.lastname: Bernasconi
authors.forename: Rozen
authors.initials: R
authors.lastname: Le Panse
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009469:Neuromuscular Junction / Q000276:immunology / Q000473:pathology; D011950:Receptors, Cholinergic / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D011950:Receptors, Cholinergic; D051193:Toll-Like Receptors