Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19
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Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19. / 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; 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; Maček, Boris; Twerenbold, Raphael; Penninger, Josef M; Matter, Matthias S; Flatz, Lukas.
In: AM J RESP CRIT CARE, Vol. 207, No. 1, 01.01.2023, p. 38-49.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19
AU - Sinnberg, Tobias
AU - Lichtensteiger, Christa
AU - Ali, Omar Hasan
AU - Pop, Oltin T
AU - Jochum, Ann-Kristin
AU - Risch, Lorenz
AU - Brugger, Silvio D
AU - Velic, Ana
AU - Bomze, David
AU - Kohler, Philipp
AU - Vernazza, Pietro
AU - Albrich, Werner C
AU - Kahlert, Christian R
AU - Abdou, Marie-Therese
AU - Wyss, Nina
AU - Hofmeister, Kathrin
AU - Niessner, Heike
AU - Zinner, Carl
AU - Gilardi, Mara
AU - Tzankov, Alexandar
AU - Röcken, Martin
AU - Dulovic, Alex
AU - Shambat, Srikanth Mairpady
AU - Ruetalo, Natalia
AU - Buehler, Philipp K
AU - Scheier, Thomas C
AU - Jochum, Wolfram
AU - Kern, Lukas
AU - Henz, Samuel
AU - Schneider, Tino
AU - Kuster, Gabriela M
AU - Lampart, Maurin
AU - Siegemund, Martin
AU - Bingisser, Roland
AU - Schindler, Michael
AU - Schneiderhan-Marra, Nicole
AU - Kalbacher, Hubert
AU - McCoy, Kathy D
AU - Spengler, Werner
AU - Brutsche, Martin H
AU - Maček, Boris
AU - Twerenbold, Raphael
AU - Penninger, Josef M
AU - Matter, Matthias S
AU - Flatz, Lukas
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
KW - Humans
KW - Pulmonary Surfactants/metabolism
KW - COVID-19
KW - Bronchoalveolar Lavage Fluid/chemistry
KW - Surface-Active Agents
KW - Autoantibodies
KW - Immunoglobulin A
U2 - 10.1164/rccm.202201-0011OC
DO - 10.1164/rccm.202201-0011OC
M3 - SCORING: Journal article
C2 - 35926164
VL - 207
SP - 38
EP - 49
JO - AM J RESP CRIT CARE
JF - AM J RESP CRIT CARE
SN - 1073-449X
IS - 1
ER -
