MD B2: Investigation of cigarette smoking-induced autoantibodies against human airway epithelial cells in patient with COPD

Background. Cigarette smoking (CS) is associated with numerous human diseases, including autoimmune disorders. Growing evidence suggest that CS-induced autoimmunity is a hallmark of in chronic obstructive pulmonary disease (COPD) and its animal models. However, it remains elusive whether CS-induced autoimmune responses contribute to the development of COPD. Our previous study demonstrates that sera of COPD patients are featured by increased levels of autoantibodies against extracellular antigens. Moreover, it has been shown that autoantibodies in plasma of COPD patients are capable to induce antibody-dependent cell-mediated cytotoxicity (ADCC) of human primary pulmonary epithelial cells. Therefore, here we hypothesize that CS exposure induces the production of pathogenic autoantibodies against airway epithelial cells and thus contribute to the development of COPD. 

Objectives. In this project, we aim to identify the antigen-specificity and pathogenicity of autoantibodies against epithelial cell induced by CS exposure. 

Work program. For this purpose, we will utilize human primary airway epithelial cells to quantify levels of autoantibodies against epithelial cell in sera of COPD patients using flow cytometry. Subsequently, antigen-specificity of anti-epithelial IgG will be determined using immunoprecipitation and N-terminal protein sequencing. Finally, pathogenicity of antigen-specific autoantibodies will be evaluated in vitro with human primary airway epithelial cells using the ADCC assay.