The severity of myasthenia gravis correlates with the serum concentration of titin and ryanodine receptor antibodies.
BACKGROUND
Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor (AChR). Non-AChR muscle autoantibodies are present in many MG serum samples, mainly from patients with thymoma or late-onset MG. The exact relationship between MG severity and several non-AChR muscle antibodies is unknown.


OBJECTIVE
To study the correlation between the severity of MG and the concentration of antibodies against striated muscle tissue sections, titin, citric acid antigen, ryanodine receptor, and AChR.


METHODS
The severity of MG was graded in 146 consecutive patients with MG, and their serum samples were tested for the presence of autoantibodies. Ten patients who were titin antibody positive were observed in longitudinal follow-up.


RESULTS
No significant difference was found in MG severity between late-onset and thymoma MG. Titin, citric acid antigen, and ryanodine receptor antibodies occurred significantly more often among patients with severe MG than among patients with less severe disease. Changes in MG severity correlated with changes in titin antibody titer in the individual patient. Titin antibodies showed a better longitudinal correlation with disease severity than the AChR antibodies.


CONCLUSIONS
Non-AChR muscle autoantibodies occurred more frequently in severe MG regardless of MG subgroup. Thymoma per se does not generate a more severe MG. It may well be the presence of a humoral immune response to non-AChR muscle antigens such as titin, citric acid antigen, and ryanodine receptor that leads to a severe disease, not the presence of thymoma or a late age of onset. These antibodies can serve as important prognostic markers in MG regardless of the presence of thymoma.
Romi
F
F
Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway. fredrik.romi@haukeland.no
Skeie
G O
GO
Aarli
J A
JA
Gilhus
N E
NE
D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D019343:Citric Acid / Q000276:immunology*; D064211:Connectin; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000276:immunology*; D018482:Muscle, Skeletal / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology*; D011494:Protein Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000276:immunology*; D012720:Severity of Illness Index; D013945:Thymoma / Q000150:complications; D013953:Thymus Neoplasms / Q000150:complications
D001323:Autoantibodies; D064211:Connectin; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; C577285:TTN protein, human; D019343:Citric Acid; D011494:Protein Kinases