β2-Adrenergic receptor antibodies in myasthenia gravis

Although autoantibodies against the nicotinic acetylcholine receptor are the characteristic feature of the autoimmune disease myasthenia gravis (MG), no strong correlation is found between the autoantibody titer and the degree of clinical severity. Numerous studies have attempted to detect the presence of other autoantibody populations that might have a role in the pathology of the disease. We report, for the first time, that 18% of the MG patients we screened have antibodies in their serum to a peptide corresponding to the second extracellular loop of the human β2-adrenergic receptor (residues 172–197). Affinity purified antibodies to the β2-adrenergic receptor peptide 172–197 reacted with the human β2-adrenergic receptor protein obtained from transfected E. coli cell membrane extracts, but did not cross-react with the human AChR. Sufficient material was obtained from nine MG patients and it was found that the gamma globulin fraction from these patients immunoprecipitated the receptor, and that affinity purified IgG to peptide 172–197 competed for receptor binding with the β-antagonist iodo-cyanopindolol. Using truncated peptides or amino acid modification procedures, no immunodominant B-cell epitope could be detected within region 172–197. Thus, a subpopulation of MG patients possesses anti-β2-adrenergic receptor antibodies which are a distinct set of autoantibodies with possible pharmacological activity.