Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19.
Journal Paper/Review - Jan 1, 2023
Sinnberg Tobias, Lichtensteiger Christa, Ali Omar Hasan, Pop Oltin T, Risch Lorenz, Brugger Silvio D, Velic Ana, Bomze David, Kohler Philipp, Vernazza Pietro, Albrich Werner C, Kahlert Christian R, Abdou Marie-Therese, Wyss Nina, Hofmeister Kathrin, Niessner Heike, Zinner Carl, Gilardi Mara, Tzankov Alexandar, Röcken Martin, Dulovic Alex, Shambat Srikanth Mairpady, Ruetalo Natalia, Buehler Philipp K, Scheier Thomas C, Jochum Wolfram, Kern Lukas, Henz Samuel, Schneider Tino, Kuster Gabriela M, Lampart Maurin, Siegemund Martin, Bingisser Roland, Schindler Michael, Schneiderhan-Marra Nicole, Kalbacher Hubert, McCoy Kathy D, Spengler Werner, Brutsche Martin H, Macek Boris, Twerenbold Raphael, Penninger Josef M, Matter Matthias S, Flatz Lukas, Jochum Ann-Kristin
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. To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. 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. 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. 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.