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

Content Provider	Europe PMC
Author	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
Copyright Year	2023
Abstract	RationaleCoronavirus 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.ObjectivesTo assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity.MethodsWe 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 ResultsIgA 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.ConclusionsOur 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.
Page Count	12
ISSN	1073449X
Journal	American Journal of Respiratory and Critical Care Medicine
Volume Number	207
PubMed Central reference number	PMC9952873
Issue Number	1
PubMed reference number	35926164
e-ISSN	15354970
DOI	10.1164/rccm.202201-0011OC
Language	English
Publisher	American Thoracic Society
Publisher Date	2023-01-01
Access Restriction	Open
Rights License	This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern (dgern@thoracic.org). Copyright © 2023 by the American Thoracic Society
Subject Keyword	COVID-19 autoimmunity immunoglobulin A pulmonary surfactant pulmonary-associated surfactant protein
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine Critical Care and Intensive Care Medicine