Human Plasma-Derived IgG Protects Against Respiratory Pathogens in an Epithelial Air-Liquid Interface Model

Recurrent respiratory tract infections are a hallmark of COPD and bronchiectasis. The role of respiratory tract immunoglobulins in chronic airway diseases is still unclear. Here, we investigated whether human plasma-derived IgG preparations have specificities against respiratory pathogens and whether IgG can attenuate the sequelae of infection in vitro. We hypothesize that local IgG treatment of the respiratory tract will reduce pathogen burden, inflammation and as a consequence lower exacerbation risk in patients with chronic airway disease. We conducted experiments to study the interaction of IgG, mucins and pathogens at the respiratory epithelium to gain a better understanding of the dynamic events leading to pathogen binding and elimination. We used a 3D pseudostratified in vitro epithelial air-liquid interface tissue culture model (MucilAir™) derived from healthy individuals and patients with COPD. We conducted functional studies with viral and bacterial agents to investigate IgG-pathogen interactions and dynamics in the mucus environment. We showed that plasma-derived IgG contains antibody specificities against respiratory pathogens, including viral (rhinovirus, influenza virus) and bacterial agents (S. pneumoniae and P. aeruginosa). In vitro, plasma-derived IgG protected epithelial cultures against viral infections and maintained epithelial integrity, cilia beating frequency, and mucociliary clearance. Studies are ongoing to investigate the dynamics of plasma-derived IgG and pathogen in the mucus environment. These studies support a contribution of topically applied human plasma-derived IgG to humoral immune defence at the mucosal barrier in chronic airway diseases.