title: Autoimmune mechanisms in myasthenia gravis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The recent identification of mechanisms initiating and perpetuating autoimmunity in myasthenia gravis may stimulate the development of more effective therapies.
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: Pia
authors.initials: P
authors.lastname: Bernasconi
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology; D009469:Neuromuscular Junction / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents