IgA autoantibodies target pulmonary surfactant in patients with severe COVID-19

Sinnberg, T.; Lichtensteiger, C.; Hasan Ali, O.; Pop, O. T.; Gilardi, M.; Risch, L.; Bomze, D.; Kohler, P.; Vernazza, P.; Albrich, W. C.; Kahlert, C. R.; Brugger, S. D.; Abdou, M.-T.; Zinnber, C.; Tzankov, A.; Roecken, M.; Kern, L.; Brutsche, M. H.; Kalbacher, H.; Velic, A.; Macek, B.; Penninger, J. M.; Matter, M. S.; Flatz, L.

Complications affecting the lung are hallmarks of severe coronavirus disease 2019 (COVID-19). While there is evidence for autoimmunity in severe COVID-19, the exact mechanisms remain unknown. Here, we established a prospective observational cohort to study lung specific autoantibodies (auto-Abs). Incubation of plasma from severe COVID-19 patients with healthy human lung tissue revealed the presence of IgA antibodies binding to surfactant-producing pneumocytes. Enzyme-linked immunosorbent assays (ELISA) and protein pull-downs using porcine surfactant confirmed the presence of auto-Abs binding to surfactant proteins in severe COVID-19 patients. Mass spectrometry and ELISAs with recombinant proteins identified IgA auto-Abs that target human surfactant proteins B and C. In line with these findings, lungs of deceased COVID-19 patients showed reduced pulmonary surfactant. Our data suggest that IgA-driven autoimmunity against surfactant may result in disease progression of COVID-19.