{"article_processing_charge":"Yes (in subscription journal)","date_published":"2024-09-10T00:00:00Z","pmid":1,"department":[{"_id":"MiSi"}],"day":"10","year":"2024","date_updated":"2024-09-30T09:17:19Z","author":[{"last_name":"Stark","first_name":"Konstantin","full_name":"Stark, Konstantin"},{"full_name":"Kilani, Badr","first_name":"Badr","last_name":"Kilani"},{"first_name":"Sven","full_name":"Stockhausen, Sven","last_name":"Stockhausen"},{"first_name":"Johanna","full_name":"Busse, Johanna","last_name":"Busse"},{"last_name":"Schubert","full_name":"Schubert, Irene","first_name":"Irene"},{"last_name":"Tran","first_name":"Thuy Duong","full_name":"Tran, Thuy Duong"},{"last_name":"Gärtner","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","first_name":"Florian R","full_name":"Gärtner, Florian R"},{"last_name":"Leunig","full_name":"Leunig, Alexander","first_name":"Alexander"},{"last_name":"Pekayvaz","full_name":"Pekayvaz, Kami","first_name":"Kami"},{"first_name":"Leo","full_name":"Nicolai, Leo","last_name":"Nicolai"},{"first_name":"Valeria","full_name":"Fumagalli, Valeria","last_name":"Fumagalli"},{"last_name":"Stermann","first_name":"Julia","full_name":"Stermann, Julia"},{"last_name":"Stephan","full_name":"Stephan, Felix","first_name":"Felix"},{"last_name":"David","full_name":"David, Christian","first_name":"Christian"},{"first_name":"Martin B.","full_name":"Müller, Martin B.","last_name":"Müller"},{"full_name":"Heyman, Birgitta","first_name":"Birgitta","last_name":"Heyman"},{"full_name":"Lux, Anja","first_name":"Anja","last_name":"Lux"},{"full_name":"Da Palma Guerreiro, Alexandra","first_name":"Alexandra","last_name":"Da Palma Guerreiro"},{"last_name":"Frenzel","full_name":"Frenzel, Lukas P.","first_name":"Lukas P."},{"last_name":"Schmidt","full_name":"Schmidt, Christoph Q.","first_name":"Christoph Q."},{"first_name":"Arthur","full_name":"Dopler, Arthur","last_name":"Dopler"},{"first_name":"Markus","full_name":"Moser, Markus","last_name":"Moser"},{"last_name":"Chandraratne","full_name":"Chandraratne, Sue","first_name":"Sue"},{"first_name":"Marie Luise","full_name":"Von Brühl, Marie Luise","last_name":"Von Brühl"},{"first_name":"Michael","full_name":"Lorenz, Michael","last_name":"Lorenz"},{"last_name":"Korff","first_name":"Thomas","full_name":"Korff, Thomas"},{"last_name":"Rudelius","full_name":"Rudelius, Martina","first_name":"Martina"},{"full_name":"Popp, Oliver","first_name":"Oliver","last_name":"Popp"},{"first_name":"Marieluise","full_name":"Kirchner, Marieluise","last_name":"Kirchner"},{"first_name":"Philipp","full_name":"Mertins, Philipp","last_name":"Mertins"},{"first_name":"Falk","full_name":"Nimmerjahn, Falk","last_name":"Nimmerjahn"},{"last_name":"Iannacone","full_name":"Iannacone, Matteo","first_name":"Matteo"},{"last_name":"Sperandio","full_name":"Sperandio, Markus","first_name":"Markus"},{"full_name":"Engelmann, Bernd","first_name":"Bernd","last_name":"Engelmann"},{"first_name":"Admar","full_name":"Verschoor, Admar","last_name":"Verschoor"},{"last_name":"Massberg","full_name":"Massberg, Steffen","first_name":"Steffen"}],"file_date_updated":"2024-09-30T09:16:03Z","publication_identifier":{"eissn":["1097-4180"]},"publisher":"Elsevier","month":"09","page":"2140-2156","issue":"9","publication":"Immunity","_id":"18109","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":57,"date_created":"2024-09-22T22:01:42Z","citation":{"chicago":"Stark, Konstantin, Badr Kilani, Sven Stockhausen, Johanna Busse, Irene Schubert, Thuy Duong Tran, Florian R Gärtner, et al. “Antibodies and Complement Are Key Drivers of Thrombosis.” <i>Immunity</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.immuni.2024.08.007\">https://doi.org/10.1016/j.immuni.2024.08.007</a>.","short":"K. Stark, B. Kilani, S. Stockhausen, J. Busse, I. Schubert, T.D. Tran, F.R. Gärtner, A. Leunig, K. Pekayvaz, L. Nicolai, V. Fumagalli, J. Stermann, F. Stephan, C. David, M.B. Müller, B. Heyman, A. Lux, A. Da Palma Guerreiro, L.P. Frenzel, C.Q. Schmidt, A. Dopler, M. Moser, S. Chandraratne, M.L. Von Brühl, M. Lorenz, T. Korff, M. Rudelius, O. Popp, M. Kirchner, P. Mertins, F. Nimmerjahn, M. Iannacone, M. Sperandio, B. Engelmann, A. Verschoor, S. Massberg, Immunity 57 (2024) 2140–2156.","ama":"Stark K, Kilani B, Stockhausen S, et al. Antibodies and complement are key drivers of thrombosis. <i>Immunity</i>. 2024;57(9):2140-2156. doi:<a href=\"https://doi.org/10.1016/j.immuni.2024.08.007\">10.1016/j.immuni.2024.08.007</a>","ista":"Stark K, Kilani B, Stockhausen S, Busse J, Schubert I, Tran TD, Gärtner FR, Leunig A, Pekayvaz K, Nicolai L, Fumagalli V, Stermann J, Stephan F, David C, Müller MB, Heyman B, Lux A, Da Palma Guerreiro A, Frenzel LP, Schmidt CQ, Dopler A, Moser M, Chandraratne S, Von Brühl ML, Lorenz M, Korff T, Rudelius M, Popp O, Kirchner M, Mertins P, Nimmerjahn F, Iannacone M, Sperandio M, Engelmann B, Verschoor A, Massberg S. 2024. Antibodies and complement are key drivers of thrombosis. Immunity. 57(9), 2140–2156.","ieee":"K. Stark <i>et al.</i>, “Antibodies and complement are key drivers of thrombosis,” <i>Immunity</i>, vol. 57, no. 9. Elsevier, pp. 2140–2156, 2024.","apa":"Stark, K., Kilani, B., Stockhausen, S., Busse, J., Schubert, I., Tran, T. D., … Massberg, S. (2024). Antibodies and complement are key drivers of thrombosis. <i>Immunity</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.immuni.2024.08.007\">https://doi.org/10.1016/j.immuni.2024.08.007</a>","mla":"Stark, Konstantin, et al. “Antibodies and Complement Are Key Drivers of Thrombosis.” <i>Immunity</i>, vol. 57, no. 9, Elsevier, 2024, pp. 2140–56, doi:<a href=\"https://doi.org/10.1016/j.immuni.2024.08.007\">10.1016/j.immuni.2024.08.007</a>."},"publication_status":"published","status":"public","oa_version":"Published Version","file":[{"date_updated":"2024-09-30T09:16:03Z","date_created":"2024-09-30T09:16:03Z","relation":"main_file","success":1,"file_size":6892750,"file_id":"18162","content_type":"application/pdf","checksum":"4683de43d06a8fd8e3fc91af4ddc1ba2","creator":"dernst","access_level":"open_access","file_name":"2024_Immunity_Stark.pdf"}],"scopus_import":"1","doi":"10.1016/j.immuni.2024.08.007","article_type":"original","has_accepted_license":"1","type":"journal_article","language":[{"iso":"eng"}],"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"intvolume":"        57","external_id":{"pmid":["39226900"]},"ddc":["570"],"oa":1,"quality_controlled":"1","acknowledgement":"We thank Michael Carroll (Harvard Medical School, Boston) for providing Ighmtm1Che, C4−/−, and C3−/− mice; Mark Suter (University of Zurich, Zurich) for providing Aicda−/− mice; Marina Botto (Imperial College London, London) for providing C1q−/− and fB−/− mice; Craig Gerard (Harvard Medical School, Boston) for providing C3aR−/− mice; Falk Nimmerjahn (University Erlangen-Nuernberg, Erlangen) for providing Fcgr−/−Fcgr2b−/− mice; Karl Lang (University of Duisburg-Essen, Essen) for providing Fcmr−/− mice; Hans Hengartner and Rolf Zinkernagel (ETH Zurich, Zurich) for providing KL25 mice; Mark Zabel (University Hospital of Zurich, Zurich) for providing CR2−/− mice; Christie Ballantyne (Baylor College of Medicine, Houston) for providing CD11c−/− mice; and Siamon Gordon (University of Oxford, Oxford) for providing CD11b−/− mice. A.V. wishes to thank Michael Grünaug and dedicates this work to Annette, Rita, and Hans.\r\nThis project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. \r\n947611) (K.S.). This study was supported by the Deutsche Forschungsgemeinschaft through the collaborative research center 914 project B02 (K.S. and S.M.), project B04 (A.V.), project A01 (M.M.), project B01 (M.S.), the collaborative research center 1123 project B07 (K.S. and S.M.), the collaborative research center 359 (project A03 [K.S.] and B02 [M.S.]), the international research training group 1911 project B09 (A.V.), the clinical research unit 303 project 7 (A.V.), cluster of excellence 2167 (A.V.), collaborative research center 1526 project 05 (A.V.), the ANR-DFG project JAKPOT (K.S.), LMUexcellent (K.S.), and the Deutsche Zentrum für Herz-Kreislauf-Forschung (PostDoc Grant and partner site project [K.S. and S.M.]). M.I. is supported by the European Research Council (ERC) Advanced Grant 101141363, ERC Proof of Concept Grant 101138728, Italian Association for Cancer Research (AIRC) Grants 19891 and \r\n22737, Italian Ministry for University and Research Grants PE00000007 (INF-ACT) and PRIN \r\n2022FMESXL, Funded Research Agreement from Asher Biotherapeutics, VIR Biotechnology, and BlueJay Therapeutics. V.F. is supported by the Italian Ministry for University and Research Grants PE00000007 (INF-ACT) and Fondazione Prossimo Mio.","title":"Antibodies and complement are key drivers of thrombosis","abstract":[{"text":"Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcμR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.","lang":"eng"}]}