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- Title
Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19.
- Authors
Sinnberg, Tobias; Lichtensteiger, Christa; Ali, Omar Hasan; Pop, Oltin T.; Jochum, Ann-Kristin; 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
- 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 lungspecific 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.
- Subjects
SWITZERLAND; GERMANY; PULMONARY surfactant; INFLUENZA; AUTOANTIBODIES; MECONIUM aspiration syndrome; COVID-19; ADULT respiratory distress syndrome; SURFACE tension measurement; DESMOGLEINS
- Publication
American Journal of Respiratory & Critical Care Medicine, 2023, Vol 207, Issue 1, p38
- ISSN
1073-449X
- Publication type
Article
- DOI
10.1164/rccm.202201-0011OC