Myasthenia gravis: T and B cell reactivities to the beta-bungarotoxin binding protein presynaptic membrane receptor.
Antibodies against acetylcholine receptor (AChR) can be detected in most patients with myasthenia gravis (MG) and are considered to be involved in the immunopathogenesis of this disease. AChR are isolated from crude receptor preparations by binding to alpha-bungarotoxin (alpha-BuTx). Patients with MG have also antibodies against a second protein tentatively named presynaptic membrane receptor (PsmR), which has been isolated from crude receptor utilizing beta-bungarotoxin (beta-BuTx). PsmR could represent another antigen besides AChR relevant for the development of MG. We have now evaluated the T cell reactivity to PsmR in MG and controls by analysing the frequencies of cells which in response to PsmR in short-term cultures secreted interferon-gamma (IFN-gamma). The B cell response to PsmR was analysed in parallel by counting cells secreting anti-PsmR antibodies. Most patients with MG had PsmR reactive T cell in blood with a median number of about 1 per 44,000 mononuclear cells. Cells secreting anti-PsmR antibodies belonging to the IgG and IgA isotypes, less frequently of the IgM isotype were detected in most MG patients. A positive correlation was found between T cells reactive with PsmR and anti-PsmR IgG antibody secreting cells. PsmR reactive T and B cells were also detected in control patients, but at much lower numbers. Our results indicate that MG is accompanied by T as well as B cell responses to PsmR, in addition to the previously recognized responses to AChR. It remains to be shown whether these PsmR reactivities are of pathogenetic importance in MG.
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Department of Neurology, Karolinska Institutet, Stockholm, Sweden.
Sun
J B
JB
Lu
C Z
CZ
Xiao
B G
BG
Fredrikson
S
S
Höjeberg
B
B
Olsson
T
T
D000328:Adult; D000368:Aged; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002038:Bungarotoxins / Q000378:metabolism*; D002417:Cattle; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D009157:Myasthenia Gravis / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D011978:Receptors, Nicotinic; D013569:Synapses / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579167:Chrna7 protein, human; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor