The autoreactivity phenomenon in the pathogenesis of asthma-COPD overlap (ACO)

Abstract

The modern concept of development of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) implies the leading role of immune reactions with the true inflammatory autoimmune pathogenetic components. Aim of the study was to evaluate the autoreactivity in patients with chronic immune-mediated respiratory diseases: BA, COPD, and their combination — ACO. Methods. The study enrolled 155 patients with the average age of 49 ± 17 years old. We modified quantitative ELISA for detection of IgE and IgG4-autoantibodies using commercial tissue antigens of epithelial keratin, type III and VI collagen, myosin and elastin (Sigma, USA), conjugates of monoclonal anti-IgE or anti-IgG4 antibodies and IgE and IgG4 reference reagents (Dr. Fooke, Germany). Results. Concomitant COPD and BA symptoms were accompanied by significantly higher levels of IgE autoAbs to epithelial keratin, type III and VI collagen and myosin and were associated with a higher detection rate of these Abs, especially in severe forms of the disease (50 — 80%). The IgE-autoAbs to myosin increased in individuals with ACO as compared to BA and reached the maximum values in patients with COPD. There was an opposite trend: the frequency of detection and concentration of IgG4-autoAbs decreased with the disease severity. The levels of IgG4-autoAbs to type III and IV collagens and to elastin decreased as the obstruction worsened and were undetectable in patients with COPD and ACO. IgE and IgG4 autoAbs were inversely correlated to type VI collagen, type III collagen, elastin and myosin (r = -0.38; -0.61). The spirometry showed the inverse correlations between the increased IgE-autoAbs to type III collagen and high-speed ventilation parameters (R = -0.79; p = 0.01). So, IgE-autoAbs may be considered a factor of the progressive course of BA in combination with COPD associated with a significant bronchial obstruction. Conclusion. Thus, the detection of IgE and IgG4-AT to tissue antigens of collagen, elastin and myosin can be further used for clinical and immunological monitoring of BA and COPD, especially with their combined phenotype (ACO). The increased levels of IgE-autoAbs can be considered one of the immunological prognostic markers of intense remodeling processes in the bronchial wall. These processes are also confirmed by an increased IgE-mediated immune response to miosine and elastine EG in patients with the severe disease. The developed assay of the level of autoAbs to tissue antigens can be used in the early diagnostics of adverse course of asthma, especially ACO, and can be used as a laboratory criterion of the control over the disease when making decisions on personalized pharmacotherapy and patient management.