title: Titin and ryanodine receptor antibodies in myasthenia gravis.
abstract: Some myasthenia gravis (MG) patients have antibodies against skeletal muscle antigens in addition to the acetylcholine receptor (AChR). Two major antigens for non-AchR antibodies in MG are the Ca(2+) release channel of the sarcoplasmic reticulum, the ryanodine receptor (RyR) and titin, a gigantic filamentous muscle protein essential for muscle structure, function and development. RyR and titin antibodies are found mainly in thymoma MG patients and in a few late-onset MG patients and correlate with a severe MG disease. The presence of titin antibodies, which bind to key regions near the A/I junction and in the central I-band, correlates with myopathy. The immunosuppressant (FK506), which enhances Ca(2+) release from the RyR, seems to have a symptomatic effect on MG patients with RyR antibodies. The RyR antibodies recognize a region near the N-terminus important for channel regulation and inhibit Ca(2+) release in vitro. However, evidence that antibodies against the intracellular antigens RyR and titin are pathogenic in vivo is still missing.
authors.affiliation: Department of Clinical Medicine, University of Bergen and Department of Neurology, Haukeland University Hospital, Bergen, Norway. gske@haukeland.no
authors.forename: G O
authors.initials: GO
authors.lastname: Skeie
authors.forename: J A
authors.initials: JA
authors.lastname: Aarli
authors.forename: N E
authors.initials: NE
authors.lastname: Gilhus
mesh_terms: D000906:Antibodies / Q000502:physiology*; D064211:Connectin; D006801:Humans; D009124:Muscle Proteins / Q000276:immunology*; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D011494:Protein Kinases / Q000276:immunology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D000906:Antibodies; D064211:Connectin; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C577285:TTN protein, human; D011494:Protein Kinases