Am J Respir Crit Care Med
. 2022 Aug 4.
doi: 10.1164/rccm.202201-0011OC. Online ahead of print.
Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19
Tobias Sinnberg 1 2 , Christa Lichtensteiger 3 , Omar Hasan Ali 4 5 , Oltin T Pop 3 , Ann-Kristin Jochum 6 , Lorenz Risch 7 , Silvio D Brugger 8 , Ana Velic 9 , David Bomze 10 , Philipp Kohler 11 , Pietro Vernazza 12 , Werner C Albrich 13 , Christian R Kahlert 11 , Maire-Therese Abdou 3 , Nina Wyss 14 , Kathrin Hofmeister 1 , Heike Niessner 1 , Carl Zinner 15 , Mara Gilardi 15 , Alexandar Tzankov 15 , Martin Röcken 1 , Alex Dulovic 16 , Srikanth Mairpady Shambat 17 , Natalia Ruetalo 18 , Philipp K Buehler 19 , Thomas C Scheier 20 , Wolfram Jochum 21 , Lukas Kern 22 , Samuel Henz 23 , Tino Schneider 24 , Gabriela M Kuster 25 , Maurin Lampart 25 , Martin Siegemund 26 , Roland Bingisser 27 , Michael Schindler 18 , Nicole Schneiderhan-Marra 16 , Hubert Kalbacher 28 , Kathy D McCoy 29 , Werner Spengler 30 , Martin H Brutsche 31 , Boris Macek 9 , Raphael Twerenbold 32 , Josef M Penninger 33 34 , Matthias S Matter 15 , Lukas Flatz 35
Affiliations
- PMID: 35926164
- DOI: 10.1164/rccm.202201-0011OC
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 bronchoalveolar lavage 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 bronchoalveolar lavage 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 against pulmonary surfactant proteins B and C and that these antibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: COVID-19; IgA; autoimmunity; pulmonary surfactant; pulmonary-associated surfactant protein.