Three Types of Striational Antibodies in Myasthenia Gravis

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 Ca^2+ 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