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 < 0.005). The 49-kD auto-antigen 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.

Lee Y, et al. Allergy Asthma Immunol Res. 2021 Sep;13(5):733-745. https://doi.org/10.4168/aair.2021.13.5.733

Lee JH, et al. Yonsei Med J. 2019 Jun;60(6):570-577. https://doi.org/10.3349/ymj.2019.60.6.570

The antigenic specificity and pathogenetic significance of immunoglobulins in airway secretion from asthmatic patients have not been established. Elevated levels of B-cells and immunoglobulin (Ig)A antibodies have been reported in sputum of asthmatics and these levels correlated with the eosinophil counts and levels of degranulated cytotoxic proteins from eosinophils. This study aimed to investigate the antigen specificity and possible pathogenetic significance of antibodies in airway secretion from asthmatic patients. Specific IgA and IgG antibodies to both allergen (Dermatophagoides farinae) and bacterial antigen (capsular polysaccharide antigen from Streptococcus pneumoniae) were measured in sputum from 16 atopic asthmatic patients sensitized to D. farinae and 12 nonatopic, nonasthmatic controls by enzyme-linked immunosorbent assay. Sputum was induced by inhalation of hypertonic saline. Eosinophil cationic protein (ECP) levels in sputum from asthmatic patients were measured by the Pharmacia CAP system. Levels of IgA to both D. farinae and S. pneumoniae and IgG to D. farinae in the sputum from asthmatic patients were significantly higher than those from controls (p<0.005). No significant difference was found in the levels of IgG to S. pneumoniae between the two groups. In asthmatic patients, there were significant correlations between IgA to D. farinae and S. pneumoniae (r=0.76, p=0.003). Sputum ECP levels correlated significantly with IgA to D. farinae (r=0.55, p=0.03) and S. pneumoniae (r=0.56, p=0.03) and IgG to D. farinae (r=0.52, p=0.04), but not with IgG to S. pneumoniae in asthmatic patients. In conclusion, specific immunoglobulin A antibodies to both allergen and bacterial antigen were elevated in induced sputum from atopic asthmatics and their possible involvement in eosinophil degranulation was suggested.