Increased IgG Antibody-Induced Cytotoxicity Against Airway Epithelial Cells in Patients with Nonallergic Asthma

Abstract

Background IgG autoantibodies to airway epithelial cell proteins have been detected in patients with nonallergic asthma. Objective and Methods To evaluate the functional significance of these autoantibodies, we examined the presence of IgG antibody-induced cytotoxicity against airway epithelial cells (A549) by the microcytotoxicity assay using IgG antibodies purified from patients with nonallergic asthma. Results IgG antibody-induced cytotoxicity (expressed as percent cell lysis) was significantly increased in nine patients with nonallergic asthma (mean ± standard deviation; 30.6±7.3%) as compared with eight healthy controls (13.9±5.1%) and nine patients with allergic asthma (20.3± 10.4%; p<0.05). In addition, IgG antibody-induced cytotoxicity was significantly inhibited when IgG antibodies from patients with nonallergic asthma were pre-incubated with recombinant human airway epithelial cell autoantigens (cytokeratin 18 or alpha-enolase proteins; p<0.05). Conclusion These results suggest a possible involvement of IgG autoantibody-induced cytotoxicity against airway epithelial cells in the pathogenesis of nonallergic asthma.

Highly Cytokinergic IgE Antibodies and Autoimmune Mechanisms

“…Several environmental allergens sharing structural similarities with human proteins can be autoantigens 14-16. Some tissue antigens were thought to be derived from thyroid proteins and epithelial cells interacting with environmental factors 9,10,17. This study5 also confirmed the presence of human IgE antibodies reacting to thyroglobulin, which is closely associated with the autoimmunity of chronic urticaria 11.…”

“…Several studies have suggested that autoimmune mechanisms play an important part in the development and progression of chronic allergic inflammation in subsets of asthma,9,10 chronic urticaria,11 and atopic dermatitis patients 12. Moreover, the chronic urticaria patients with high specific IgE to thyroid peroxidase showed a favorable response to anti-IgE therapy 13.…”

Untangling asthma phenotypes and endotypes

“…Autoreactive immune mechanisms induced either by molecular mimicry or as a consequence of chronic allergic inflammation and the generation of cytotoxic autoantibodies have been described (33). IgG antibodies directed against epithelial proteins, such as cytokeratin-18, have been detected in adults with intrinsic asthma (33) where dysregulated epithelial repair and impaired resolution of the inflammation might also play a role.…”

Pathophysiology of allergic inflammation

“…Circulating antibodies to cytokeratin‐18 and α‐enolase, which occur in epithelial cells, have been described in patients with intrinsic asthma and more severe asthma (61, 62). IgG autoantibodies from patients with intrinsic asthma have cytotoxic effects on epithelial cells, whereas these antibodies are not found in extrinsic asthma (63). It is possible that these autoantibodies damage airway epithelial cells so that superantigen‐producing organisms are able to more easily infect the airway surface.…”