T And B Lymphocytes Reacting With The Extracellular Loop Of The Beta(2)-Adrenergic Receptor (Beta(2)Ar) 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(2)AR (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(2)AR 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(2)AR-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(2)AR-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(2)AR-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.