Table 1.
Three types of striational antibodies in myasthenia gravis (MG).
| Autoantigen | Titin | Ryanodine receptor | Voltage-gated K channel (VGKC) |
|---|---|---|---|
| (RyR) | Kv1.4 | ||
| Molecular structure | Skeletal and cardiac sarcomere | RyR1: skeletal type | Brain, nerve, skeletal, and heart muscles |
| Giant protein (3000 kD) | RyR2: cardiac type | Homo- or hetero-tetramers | |
| Repetitive structure | 565 kD with 4 homologous subunits | One α-subunit (73 kD) | |
| Original report | Aarli et al. 1990 [7] | Mygland et al. 1992 [11] | Suzuki et al. 2005 [13] |
| Antibodies detection | ELISA (commercially available) | ELISA, Western blot | Immunoprecipitation assay |
| Myasthenia gravis titin-30 (MGT-30) near the A/I-band junction | Epitopes in both RyR1 and RyR2 | 35-S-labeled rabdomyosarcoma cell | |
| Sarcoplasmic reticulum from rabbit skeletal muscle N- and C-terminus of RyR1 sequence | Band at 70 kD | ||
| Epidemiology | 20–40% in all MG patients | 13–38% in all MG patients | 12–15% in all MG patients |
| 60–80% in MG patients older than 60 years | Mean onset age: 57 years | Mean onset age: 49 years | |
| 32% in nonthymoma MG patients older than 50 years | M : F = 1 : 1 | M : F = 1 : 1 | |
| Immunopathogenesis | T cell proliferative response to MGT-30 | Complement activation | Different from neuronal VGKC |
| Complement activation | Inhibiting Ca2+ release from sarcoplasmic reticulum | QT prolongation on electrocardiogram | |
| Myopathy in electromyogram | Autoantibodies to dihydropyridine receptor | ||
| Association with DR7 in Caucasians | or transient receptor potential canonical type-3 | ||
| Inhibiting excitation-contraction coupling | |||
| Thymoma-associated MG (T-MG) | 49–95% in T-MG | 70–80% in T-MG | 40–70% in T-MG |
| Titin epitope expression | RyR epitope expression | Kv1.4 mRNA expression | |
| Production from clonal thymic B cells | Diagnosis of thymoma | ||
| Diagnosis of thymoma (younger than 50 years) | C-terminal regions in RyR1 as epitope | ||
| Clinical presentation | Association with severe MG | More severe than anti-titin | More severe with anti-titin |
| Concomitant with myositis | Bulbar, respiratory, and neck involvement | Bulbar involvement and myasthenic crisisMyocarditis and/or myositis | |
| Myocarditis and/or myositis | Lethal arrhythmias | ||
| Treatment and management | Some late-onset MG with ocular type | Early pharmacological effect of tacrolimus | Responder to calcineurin inhibitors |
| poor prognosis in invasive thymoma | Sudden death | ||