Receptor-specific functional properties of beta 2-adrenergic receptor autoantibodies in asthma.

beta 2-Adrenergic receptor (beta 2 AR) autoantibodies have been reported in the serum from subjects with asthma but the functional significance of such antibodies is not known. To characterize these antibodies, we developed a Western blot (WB) technique that utilized overexpressed recombinant human beta 2AR as antigen and also developed a control antisera in rabbits directed against the C-terminus of the receptor. beta 2AR autoantibodies were detected in approximately 5% of normal subjects and in approximately 40% of asthmatic subjects. Eighty-four percent of these antibodies were of the IgG class, with the remainder being IgM. Most (73%) of WB-positive sera inhibited [125I]cyanopindolol binding to recombinant solubilized receptors. The mean binding inhibition was 40.4 +/- 5.1% for WB-positive sera versus 7.6 +/- 1.2% for WB-negative sera. Binding of antibody to beta 2AR expressed on intact cells significantly depressed receptor function, with a > 50% attenuation of isoproterenol-stimulated cAMP productio...