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Autoimmune mechanisms in myasthenia gravis

Cavalcante, Paola; Bernasconi, Pia; Mantegazza, Renato

doi: 10.1097/WCO.0b013e328357a829
NEUROMUSCULAR DISEASE: MUSCLE: Edited by Tom Rando

Purpose of review This article reviews recent findings on factors and mechanisms implicated in the pathogenesis of myasthenia gravis and briefly summarizes data on therapies acting at various stages of the autoimmune process.

Recent findings Data published over the last year promise to improve understanding of pathogenic mechanisms underlying myasthenia gravis. Animal studies have at last shown that antimuscle-specific kinase (MuSK) autoantibodies, like antiacetylcholine receptor (AChR) autoantibodies, are myasthenogenic. A new autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), has been identified in variable proportions of otherwise seronegative patients. Anti-LRP4 antibodies may define a new myasthenia gravis subtype, supporting the concept that myasthenia gravis is not a single disease entity, and that different subtypes can differ in aetiology. Genetic and environmental factors are implicated in myasthenia gravis. The finding of persisting viral infection in the thymus of AChR-myasthenia gravis patients, combined with data on chronic inflammation, suggest that pathogens may favour intrathymic AChR-specific autosensitization and maintenance of autoimmunity in genetically susceptible individuals. Defective immunoregulatory mechanisms, involving pathogenic Th17 and regulatory T cells, contribute to tolerance loss and perpetuation of the autoimmune response in myasthenia gravis patients.

Summary The recent identification of mechanisms initiating and perpetuating autoimmunity in myasthenia gravis may stimulate the development of more effective therapies.

Department of Neurology IV, Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico ‘Carlo Besta’, Milan, Italy

Correspondence to Dr Renato Mantegazza, Department of Neurology IV, Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico ‘Carlo Besta’, Via Celoria 11, 20133 Milan, Italy. Tel: +39 02 23942372/2282; fax: +39 02 70633874; e-mail: rmantegazza@istituto-besta.it

© 2012 Lippincott Williams & Wilkins, Inc.