Antibodies against the calcium channel beta-subunit in Lambert-Eaton myasthenic syndrome.
The sera of patients with Lambert-Eaton myasthenic syndrome (LEMS) contain autoantibodies against several extracellular and intracellular components of the voltage-gated calcium channel (VGCC)/synaptic vesicle release complex. An example of the latter are anti-beta-subunit antibodies (anti-MysB antibodies). We constructed a full-length cDNA clone of a human VGCC beta-subunit to produce purified beta-subunit fusion protein (MysB protein). Using this protein, we demonstrated that anti-beta-subunit antibodies are present in the sera of 23% of LEMS patients and only, in low titer, in 2% of small cell lung cancer patients without LEMS. The presence of anti-beta-subunit antibodies was closely associated with high titers of P/Q- and N-type VGCC antibodies. Immunization of rats with the purified MysB protein induced high antibody titers, but no signs of neurologic dysfunction were found. We conclude that anti-beta-subunit antibodies are not likely to interfere with ion channel function, but their presence could explain the cross-reactivity of LEMS sera with several subtypes of VGCCs and the lack of correlation between anti-VGCC antibody titer and clinical severity of disease.
Verschuuren
J J
JJ
Department of Neurology, Leiden University Hospital, The Netherlands.
Dalmau
J
J
Tunkel
R
R
Lang
B
B
Graus
F
F
Schramm
L
L
Posner
J B
JB
Newsom-Davis
J
J
Rosenfeld
M R
MR
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001782:Blood Donors; D015220:Calcium Channels / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D020746:Calcium Channels, L-Type; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003001:Cloning, Molecular; D004594:Electrophysiology; D005260:Female; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012016:Reference Values
D001323:Autoantibodies; C079146:CACNA1C protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins