Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19
Tobias Sinnberg, Christa Lichtensteiger, Omar Hasan Ali, Oltin T. Pop, Ann-Kristin Jochum, Lorenz Risch, Silvio D. Brugger, Ana Velić, David Bomze, Philipp Köhler, Pietro Vernazza, Werner C. Albrich, Christian R. Kahlert, Marie-Therese Abdou, Nina Wyss, Kathrin Hofmeister, Heike Niessner, Carl Zinner, Mara Gilardi, Alexandar Tzankov, Martin Röcken, Alex Dulovic, Srikanth Mairpady Shambat, Natalia Ruétalo, Philipp K. Buehler, Thomas Scheier, Wolfram Jochum, Lukas Kern, Samuel Henz, Tino Schneider, Gabriela M. Kuster, Maurin Lampart, Martin Siegemund, Roland Bingisser, Michael Schindler, Nicole Schneiderhan‐Marra, Hubert Kalbacher, Kathy D. McCoy, Werner Spengler, Martin Brutsche, Boris Maček, Raphael Twerenbold, Josef Penninger, Matthias S. Matter, Lukas Flatz
Abstract
Abstract Rationale Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.