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.