Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19.

Sinnberg, Tobias; Lichtensteiger, Christa; Hasan Ali, Omar; 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, Maire-Therese; Wyss, Nina; Hofmeister, Kathrin; Niessner, Heike; Zinner, Carl; Gilardi, Mara; Tzankov, Alexandar; ... (2023). Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19. American journal of respiratory and critical care medicine, 207(1), pp. 38-49. American Lung Association 10.1164/rccm.202201-0011OC

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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/).

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