Titin and ryanodine receptor antibodies in myasthenia gravis.
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.
Skeie
G O
GO
Department of Clinical Medicine, University of Bergen and Department of Neurology, Haukeland University Hospital, Bergen, Norway. gske@haukeland.no
Aarli
J A
JA
Gilhus
N E
NE
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
D000906:Antibodies; D064211:Connectin; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C577285:TTN protein, human; D011494:Protein Kinases