Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19

Florian Tran; Danielle M M Harris; Alena Scharmacher; Hanna Graßhoff; Kristina Sterner; Susanne Schinke; Nadja Käding; Jens Y Humrich; Otávio Cabral-Marques; Joana P Bernardes; Neha Mishra; Thomas Bahmer; Jeanette Franzenburg; Bimba F Hoyer; Andreas Glück; Martina Guggeis; Alexander Ossysek; Andre Küller; Derk Frank; Christoph Lange; Jan Rupp; Jan Heyckendorf; Karoline I Gaede; Howard Amital; Philip Rosenstiel; Yehuda Shoenfeld; Gilad Halpert; Avi Z Rosenberg; Kai Schulze-Forster; Harald Heidecke; Gabriela Riemekasten; Stefan Schreiber

doi:10.1183/23120541.00379-2022

Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19

ERJ Open Res. 2022 Dec 27;8(4):00379-2022. doi: 10.1183/23120541.00379-2022. eCollection 2022 Oct.

Authors

Florian Tran^{1

2}, Danielle M M Harris^{1

3}, Alena Scharmacher¹, Hanna Graßhoff⁴, Kristina Sterner⁴, Susanne Schinke⁴, Nadja Käding⁵, Jens Y Humrich⁴, Otávio Cabral-Marques^{6

7

8

9

10}, Joana P Bernardes¹, Neha Mishra¹, Thomas Bahmer^{2

11}, Jeanette Franzenburg^{1

12}, Bimba F Hoyer¹³, Andreas Glück², Martina Guggeis^{1

2}, Alexander Ossysek¹, Andre Küller¹⁴, Derk Frank^{14

15}, Christoph Lange^{16

17

18

19}, Jan Rupp⁵, Jan Heyckendorf^{2

16

17

20}, Karoline I Gaede^{16

17

20

21}, Howard Amital²², Philip Rosenstiel¹, Yehuda Shoenfeld^{22

23

24}, Gilad Halpert²², Avi Z Rosenberg²⁵, Kai Schulze-Forster²⁶, Harald Heidecke²⁶, Gabriela Riemekasten^{3

27

28}, Stefan Schreiber^{1

2

28}

Affiliations

¹ Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
² Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany.
³ Institute for Human Nutrition and Food Science, University Medical Center Schleswig-Holstein, Kiel, Germany.
⁴ Department of Rheumatology and Clinical Immunology, University Medical Center Schleswig-Holstein, Lübeck, Germany.
⁵ Department of Infectious Diseases and Microbiology, University Medical Center Schleswig-Holstein, Lübeck, Germany.
⁶ Department of Immunology, Instituto de Ciencias Biomedicas, Universidade de São Paulo, São Paulo, SP, Brazil.
⁷ Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
⁸ Network of Immunity in Infection, Malignancy, and Autoimmunity, Universal Scientific Education and Research Network, Sao Paulo, SP, Brazil.
⁹ Department of Medicine, Division of Molecular Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
¹⁰ Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil.
¹¹ LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
¹² Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein, Kiel, Germany.
¹³ Section for Rheumatology, Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany.
¹⁴ Department of Internal Medicine III, University Medical Center Schleswig-Holstein, Kiel, Germany.
¹⁵ German Centre for Cardiovascular Research (DZHK), partner site Hamburg, Kiel, Lübeck, Germany.
¹⁶ Research Center Borstel, Borstel, Germany.
¹⁷ German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems, Borstel, Germany.
¹⁸ Respiratory Medicine and International Health, University of Lübeck, Lübeck, Germany.
¹⁹ Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
²⁰ Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany.
²¹ BioMaterialBank Nord, Borstel, Germany.
²² Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Ramat-Gan, Israel.
²³ Ariel University, Ariel, Israel.
²⁴ Laboratory of the Mosaic of Autoimmunity, Saint Petersburg State University, Saint-Petersburg, Russia.
²⁵ Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
²⁶ CellTrend GmbH, Luckenwalde, Germany.
²⁷ Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany.
²⁸ These authors contributed equally.

Abstract

In patients with severe #COVID19, increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. https://bit.ly/3pqM9Vv.