Atopy, autonomic function and beta-adrenergic receptor autoantibodies.
Atopic individuals (with asthma, allergic rhinitis or atopic eczema) have impaired sensitivity to beta-adrenergic agents. After the finding of antibodies to the beta-adrenergic receptor in the serum of a subject with allergic rhinitis, coded sera from atopic and control subjects were assayed for immunoglobulins that inhibited the specific binding of 125I-labelled hydroxybenzylpindolol to beta-receptors in mammalian lung membranes. Antibodies were present in nine of 60 subjects: 3/19 normal control subjects, 1/9 pre-allergic, 4/17 asthma, 0/8 allergic rhinitis, and 1/7 cystic fibrosis patients. Antibodies of the IgG class in these sera were also demonstrated by indirect precipitation of solubilized lung beta-receptors. The autonomic sensitivity of the nine antibody-positive subjects (Ab+) was compared with that of antibody-negative subjects (Ab-). The Ab+ subjects required 15.0 +/- 1.9 ng isoprenaline (isoproterenol) kg-1 min-1 i.v. to increase pulse pressure by at least 22 mmHg (Ab-, 7.7 +/- 0.4; n = 20; P less than 0.001), and 12.4 +/- 1.8 ng isoprenaline kg-1 min-1 i.v. to increase plasma cyclic AMP concentrations by 50% (Ab-, 8.08 +/- 0.62; n = 13; P less than 0.02). Ab+ subjects required 2.06 +/- 0.3% phenylephrine to dilate their pupils (Ab-, 2.55 +/- 0.08; n = 57; P less than 0.05) and 0.61 +/- 0.08% carbachol to constrict their pupils (Ab-, 0.78 +/- 0.03%; n = 57; P less than 0.05). A role for autoantibodies as beta-receptor antagonists was further supported by showing that human lung cells (VA-13 line) cultured in the presence of globulins from Ab+ subjects had a markedly impaired cyclic AMP response to isoprenaline. These results suggest that autoantibodies to beta-receptors play a pathogenetic role in asthma and related disorders. They have important implications for the concept of autoimmunity.
D001323:Autoantibodies / Q000276:immunology; D001341:Autonomic Nervous System / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology; D011941:Receptors, Adrenergic / Q000276:immunology*; D011943:Receptors, Adrenergic, beta / Q000276:immunology*
D001323:Autoantibodies; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta