德国吕贝克大学Admar Verschoor等研究人员合作发现，抗体和补体是血栓形成的关键驱动因素。该项研究成果于2024年9月2日在线发表在《免疫》杂志上。

研究人员发现血流减慢使免疫球蛋白M（IgM）能够与FcμR和聚合免疫球蛋白受体（pIgR）结合，启动内皮激活和血小板募集。随后，激活的血小板的促凝表面接受抗原和FcγR无关的IgG沉积，导致经典补体激活，进而形成促血栓的恶性循环。

该机制的关键元素在人类静脉淤滞和COVID-19的失调性免疫血栓中均存在。通过药物靶向补体可以预防这种抗体驱动的血栓。因此，该研究揭示了抗体作为血栓形成的未被发掘的核心调节者。这些发现对抗体的治疗应用具有重要意义，并为在不影响止血功能的情况下靶向血栓形成提供了创新途径。

据了解，静脉血栓栓塞症（VTE）是一种常见且致命的疾病，尽管已有预防措施，其发病率仍在上升。临床观察表明，抗体浓度升高或基于抗体的治疗与血栓事件相关。然而，抗体如何促成血栓的形成尚不清楚。

附：英文原文

Title: Antibodies and complement are key drivers of thrombosis

Author: Konstantin Stark, Badr Kilani, Sven Stockhausen, Johanna Busse, Irene Schubert, Thuy-Duong Tran, Florian Gaertner, Alexander Leunig, Kami Pekayvaz, Leo Nicolai, Valeria Fumagalli, Julia Stermann, Felix Stephan, Christian David, Martin B. Müller, Birgitta Heyman, Anja Lux, Alexandra da Palma Guerreiro, Lukas P. Frenzel, Christoph Q. Schmidt, Arthur Dopler, Markus Moser, Sue Chandraratne, Marie-Luise von Brühl, Michael Lorenz, Thomas Korff, Martina Rudelius, Oliver Popp, Marieluise Kirchner, Philipp Mertins, Falk Nimmerjahn, Matteo Iannacone, Markus Sperandio, Bernd Engelmann, Admar Verschoor, Steffen Massberg

Issue&Volume: 2024-09-02

Abstract: 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.

DOI: 10.1016/j.immuni.2024.08.007

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00406-0