Publication

Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19.

Journal Paper/Review - Jan 1, 2023

Units
PubMed
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Citation
Sinnberg T, Lichtensteiger C, Ali O, Pop O, Risch L, Brugger S, Velic A, Bomze D, Kohler P, Vernazza P, Albrich W, Kahlert C, Abdou M, Wyss N, Hofmeister K, Niessner H, Zinner C, Gilardi M, Tzankov A, Röcken M, Dulovic A, Shambat S, Ruetalo N, Buehler P, Scheier T, Jochum W, Kern L, Henz S, Schneider T, Kuster G, Lampart M, Siegemund M, Bingisser R, Schindler M, Schneiderhan-Marra N, Kalbacher H, McCoy K, Spengler W, Brutsche M, Macek B, Twerenbold R, Penninger J, Matter M, Flatz L, Jochum A. Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19. Am J Respir Crit Care Med 2023; 207:38-49.
Type
Journal Paper/Review (English)
Journal
Am J Respir Crit Care Med 2023; 207
Publication Date
Jan 1, 2023
Issn Electronic
1535-4970
Pages
38-49
Brief description/objective

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.