Venous thromboembolism (VTE) is a life-threatening blood clot which its frequency is increasing worldwide despite preventive measures. The role of antibodies in immune defence has long been known, but this study brings surprising new findings: IgM and IgG antibodies, regardless of their specificity to a particular antigen, promote the formation of blood clots.
Antibodies as the key to thrombosis formation
IgM antibodies bind to endothelial cells that line the blood vessels and activate them, which triggers the accumulation of platelets. This phase is the first step in the formation of a thrombus. IgG antibodies then attach to activated platelets and trigger the complement system, which initiates a cascade of biochemical processes that intensify thrombosis formation through inflammatory processes.
‘Our study shows that antibodies and the complement system play a previously underestimated role in the development of thrombosis, regardless of which antigens the antibodies recognise,’ explains Prof. Konstantin Stark, Senior Consultant in Cardiology at the LMU Hospital in Munich and author of the study.
IgM and IgG - more than just defence players
IgM and IgG are reffered to as two of the most important antibodies in the human immune system. IgM antibodies are the first to be produced after an infection and play a decisive role in the initial defence against pathogens. They are particularly efficient in neutralising bacteria and viruses and in activating the complement system. IgG antibodies are the most abundant antibodies in the blood and are responsible for long-term immunity. They mark pathogens so that they can be more easily recognised and eliminated by immune cells.
However, the present study showed that these antibodies not only contribute to immune defence, but can also trigger and promote thrombosis. It is particularly noteworthy that this process occurs independently of the antigen specificity of the antibodies, which means that the antibodies exert their prothrombotic effects without having to recognise a specific antigen.
New therapeutic approaches: Protection against thrombosis without the risk of bleeding
One of the most important discoveries of the study shows that the targeted inhibition of the complement system can prevent thromboses. In contrast to conventional blood thinners, which often increase the risk of severe bleeding, natural blood clotting remains unaffected. The researchers found that this blockade is not only safer, but also effectively reduces thrombosis.
‘This method offers a promising new approach to prevention of thrombosis, which prevents the formation of blood clots without increasing the risk of bleeding,’ explains Prof Stark.
Relevance to COVID-19 and other diseases
The study results not only have an impact on the treatment of venous thrombosis, but also affect other diseases in which the complement system is involved.The parallels between thrombosis development and the thrombotic complications observed in severe COVID-19 cases are of particular scientific interest. In the autopsy samples from COVID-19 patients, the researchers found the same prothrombotic mechanisms as in their animal models: Antibodies and the complement system worked together to promote the formation of blood clots.
These findings could also play a role in the treatment of other immune-mediated thromboses, such as antiphospholipid syndrome. In addition, inhibition of the complement system could play a key role in the future in the treatment of thrombotic complications triggered by vaccines or antibody therapies, as it has been reported regarding COVID-19 vaccines.
Clinical application and future prospects
The possibility of specifically inhibiting the complement system without increasing the risk of bleeding could be particularly important for patients who have a high risk of both thrombosis and bleeding.
‘We are still at the beginning of clinical research of these new therapeutic approaches, but our results offer a promising perspective in the prevention of thrombosis,’ concludes Prof Stark. ‘Our research shows that we can pursue new approaches that primarily target the immune response in order to effectively and safely prevent thrombosis.’
Original publication:
Antibodies and complement are key drivers of thrombosis. Stark et al. (Immunity 2024)
Scientific contact:
Prof. Konstantin Stark, LMU Klinikum München, Konstantin.Stark@med.uni-muenchen.de
