T and B lymphocytes reacting with the extracellular loop of the beta 2-adrenergic receptor (beta 2AR) are present in the peripheral blood of patients with myasthenia gravis.
Eighteen percent of patients with myasthenia gravis (MG) have serum antibodies against a synthetic peptide corresponding to the second extracellular loop of the human beta 2AR (residues 172-197). In this study we examined T and B cell responses to the peptide, using assays to detect individual cells secreting interferon-gamma (IFN-gamma) and IL-4 or antibodies against the peptide, and by measuring thymidine incorporation in response to the peptide. The peptide from the beta 2AR induced cytokine secretion from blood mononuclear cells in 67% of MG patients, compared with 14-28% of the control groups. Cells secreting antibodies binding to the peptide were present in 54% of MG patients and in 19-28% of controls. The numbers of beta 2AR-reactive cells were higher in MG patients than in controls. Peptide-induced increase in thymidine incorporation in cells was also more frequently demonstrated in patients (26%) compared with controls (about 10%). Activation of cells was dependent on monocytes and on MHC class II DR antigen. Based on the pattern of the cytokine secretion induced, beta 2AR-reactive T cells comprise both T helper type-1 and type-2 subsets. In addition, control peptide-reactive T and B cells were much less frequently demonstrated in the patients, and the number of such cells did not differ between the groups. Our results show that beta 2AR-reactive cells are present in most patients with MG. Such autoreactive antibodies and cells might play a role in the pathogenesis of the disease by influencing the function of skeletal muscle and immune systems.
Yi
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Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
He
W
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Matell
G
G
Pirskanen
R
R
Magnusson
Y
Y
Eng
H
H
Lefvert
A K
AK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011487:Protein Conformation; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry* / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D014373:Tuberculin / Q000494:pharmacology
D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D010455:Peptides; D010835:Phytohemagglutinins; D018343:Receptors, Adrenergic, beta-2; D014373:Tuberculin; D015847:Interleukin-4; D007371:Interferon-gamma