Identification of Cytokeratin 18 as a Bronchial Epithelial Autoantigen Associated with Nonallergic Asthma

Abstract

The allergic response to common environmental agents (allergens) has been regarded as an important mechanism in the development of airway inflammation of patients with asthma. However, allergic sensitization cannot be detected in a significant number of adult patients with asthma. The etiologic mechanism responsible for nonallergic asthma has not yet been identified. The idea of a possible involvement of autoimmunity in the pathogenesis of nonallergic asthma has been proposed by earlier studies. To test for the possible presence of an autoimmune response to bronchial epithelial cell antigens in nonallergic asthma, we examined circulating autoantibodies to cultured human bronchial epithelial cells (BEAS-2B) in sera from patients with nonallergic asthma by immunoblot analysis. IgG autoantibodies to the 49-kD bronchial epithelial cell antigen were detected in 10 of 23 patients with nonallergic asthma (43%), 3 of 27 patients with allergic asthma (11%), 2 of 20 patients with systemic lupus erythematosus (10%), and 3 of 34 healthy volunteers (9%) (p Ͻ 0.005). The 49-kD autoantigen was purified and identified as cytokeratin 18 by amino acid sequencing. In this study, we identified cytokeratin 18 as a bronchial epithelial autoantigen associated with nonallergic asthma. Further studies are needed to determine the significance of autoimmunity in nonallergic asthma.

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

“…All asthmatic subjects underwent a skin-prick test with 50 common aeroallergens (Allergy Therapeutics, West Sussex, UK). Asthmatic patients were classified as having allergic asthma when the wheal diameter of any one allergen was greater than 3 mm over the negative control (normal saline), and there was a definite clinical history or objective evidence of asthmatic responses induced by allergen exposure as previously described [14]. In this study, patients with allergic asthma displayed typical clinical histories of mildto-moderate asthma, and the majority of the patients were sensitized to house dust mites.…”

“…IgG autoantibodies against airway epithelial cell proteins were detected by immunoblot analysis using a polyvinylidene difluoride (PVDF) membrane (Bio-Rad Laboratories, Hercules, CA, USA) as previously described [14]. The immunoreactivity of each serum sample was assessed by two independent investigators.…”

“…Previously, we explored the hypothesis that an autoimmune response against airway epithelial cell proteins might be involved in the pathogenesis of nonallergic asthma. While exploring the hypothesis that an autoimmune response to airway epithelial cell proteins might be involved in the pathogenesis of asthma, we have identified cytokeratin 18 and alphaenolase as airway epithelial cell autoantigens associated with nonallergic asthma and severe asthma, respectively [14,15].…”

Autologous Serum Skin Test for Autoantibodies Is Associated with Airway Hyperresponsiveness in Patients with Asthma

“…The possible involvement of autoimmunity in the pathogenesis of asthma has been proposed by few studies [15,16,17,18,19]. FcεRI is a multimeric surface receptor that is expressed exclusively as a tetramer on rodent cells, but exists as a tetramer or trimer on human cells.…”

Relationships between allergic disease and autoimmunity

“…В одном из исследований у 43 % больных НБА и 11 % -атопической БА были обнаружены IgG АТ к 49 kDа антигену эпителиальных клеток бронхов, идентифицированному как цитокератин 18, а в даль нейшем показано наличие ассоциированного с тя желой БА IgG ответа к 52 kDа ААГ эпителиальных клеток бронхов, идентичного 52 kD антигену тром боцитов и α энолазе [32]. Определяемые в сыворот ке крови у больных тяжелой БА IgG ААТ к α энола зе, как полагают, являются биологическим маркером тяжелой БА [33].…”