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IgA autoantibodies target pulmonary surfactant in patients with severe COVID-19
Tobias Sinnberg; Christa Lichtensteiger; Omar Hasan Ali; Oltin Tiberiu Pop; Mara Gilardi; Lorenz Risch; David Bomze; Philipp Kohler; Pietro Vernazza; Werner C Albrich; Christian R Kahlert; Silvio D Brugger; Marie-Therese Abdou; Carl Zinner; Alexandar Tzankov; Martin Roecken; Lukas Kern; Martin H Brutsche; Hubert Kalbacher; Ana Velic; Boris Macek; Josef M Penninger; Matthias S Matter; Lukas Flatz.
Affiliation
  • Tobias Sinnberg; Department of Dermatology, University Hospital Tuebingen, Liebermeisterstrasse 25, 72076 Tuebingen
  • Christa Lichtensteiger; Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Omar Hasan Ali; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver V6T 1Z3, Canada
  • Oltin Tiberiu Pop; Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Mara Gilardi; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland
  • Lorenz Risch; Labormedizinisches Zentrum Dr. Risch, Wuhrstrasse 14, 9490 Vaduz, Liechtenstein
  • David Bomze; Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Philipp Kohler; Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Pietro Vernazza; Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Werner C Albrich; Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Christian R Kahlert; Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Silvio D Brugger; Department of Infectious Diseases and Hospital Hygiene, University Hospital Zurich, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
  • Marie-Therese Abdou; Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Carl Zinner; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland
  • Alexandar Tzankov; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland
  • Martin Roecken; Department of Dermatology, University Hospital Tuebingen, Liebermeisterstrasse 25, 72076 Tuebingen, Germany
  • Lukas Kern; Lung Center, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Martin H Brutsche; Lung Center, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland
  • Hubert Kalbacher; Institute of Clinical Anatomy and Cell Analysis, University of Tuebingen, Oesterbergstrasse 3, 72074 Tuebingen, Germany
  • Ana Velic; Proteome Center Tuebingen, Interfaculty Institute for Cell Biology, University of Tuebingen, Auf der Morgenstelle 15, 72076 Tuebingen, Germany
  • Boris Macek; Proteome Center Tuebingen, Interfaculty Institute for Cell Biology, University of Tuebingen, Auf der Morgenstelle 15, 72076 Tuebingen, Germany
  • Josef M Penninger; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver V6T 1Z3, Canada
  • Matthias S Matter; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Schoenbeinstrasse 40, 4031 Basel, Switzerland
  • Lukas Flatz; Department of Dermatology, University Hospital Tuebingen, Liebermeisterstrasse 25, 72076 Tuebingen
Preprint in English | medRxiv | ID: ppmedrxiv-21250940
ABSTRACT
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.
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Full text: Available Collection: Preprints Database: medRxiv Type of study: Cohort_studies / Observational study / Prognostic study Language: English Year: 2021 Document type: Preprint
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Full text: Available Collection: Preprints Database: medRxiv Type of study: Cohort_studies / Observational study / Prognostic study Language: English Year: 2021 Document type: Preprint