Thromboembolism of blood vessels, which leads to myocardial infarction, strokes, and venous thromboembolism, is the leading cause of death in the Western Hemisphere. Therefore, it is crucial to understand the mechanisms that prevent clot formation. A new study by the research team Christoph Binder, Principal Investigator at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Professor at the Medical University of Vienna, explains the important role of immunoglobulin M (IgM) antibodies in preventing blood clots. The study was published in the journal blood It demonstrates that these antibodies recognize microscopic vesicles, which are membranous bubbles shed by cells and known for their critical role in blood clotting, thus preventing their pro-coagulation effects. These results provide a novel approach to reduce the risk of blood clots using IgM antibodies.
Antibodies are an important component of the immune system. On the one hand, these proteins work in the body to defend against microbes, and on the other hand, to remove “cell waste” from the body. The natural antibodies present from birth, most of which are immunoglobulin M (IgM), play an essential role in these processes. In the context of blood clotting, previous studies have shown that people with low IgM antibodies have an increased risk of clotting. A research group led by Christoph Binder, Professor of Arteriosclerosis Research at Vienna Medical University and Principal Investigator at CeMM, previously demonstrated in a study published in 2009 that a high proportion of natural IgM antibodies bind oxidative epitopes, which are molecular structures that are present on dying cells and act as “Remove signals me” for the immune system. In this study, the Binder research group identified mechanisms that explain the anticoagulant effects of natural IgM antibodies.
IgM antibodies bind to coagulation-inducing microscopic vesicles
Microcrystalline vesicles, the bubbles drooping from the cell membrane, are important mediators of blood clotting and clot formation. Study authors George Obermayr and Taras Avonyuchkin of the Binder Research Group, both affiliated with CeMM and the Medical University of Vienna, showed that natural IgM antibodies that bind specific oxidative epitopes can inhibit the coagulation and coagulation of microscopic vesicles. This provides a mechanical explanation for a previously published observation that lower levels of these antibodies are associated with an increased risk of thrombosis. Scientists say: “We hypothesize that the natural IgM antibodies recognize the microscopic vesicles that cause inflammation and specifically stimulate clotting.” In both experiments with a mouse model and direct human blood samples, the scientists were able to show that the addition of IgM antibodies inhibited blood clotting caused by microscopic vesicles and mice protected from lung thrombosis. Conversely, it was also shown that depletion of IgM antibodies increased blood clotting.
A potential starting point for future treatments
The study authors explain: “For the first time, the study provides an explanation for why people with low numbers of normal IgM antibodies have an increased risk of clotting.” “The results provide high potential for new therapies to reduce the risk of blood clots,” adds project leader Christoph Binder. “The effect on IgM antibody levels in high-risk patients could be a viable addition to the previously identified blood-thinning treatment, as this is also known to be the case.” It is associated with side effects such as increased bleeding tendency in the case of injuries. ” In addition, the study makes an important contribution to the basic understanding of thrombolytic modifying factor formation. “Microcytic vesicles are already known as an important component of blood clotting. However, our study creates a new possibility to target them therapeutically for the first time,” says Christoph Binder.
A study entitled “IgM Natural Antibodies Prevent Micro-Vesicle Clotting and Thrombosis” is published in the journal. blood, Online on December 8, 2020. DOI: https: /
Authors: George Obermayr *, Taras Avonyuchkin *, Laura Guderle, Florian Bohm, Traud Schrottmeyer, Soren Taqi, Michael Schoames, Jehan Ay, Ingrid Babinger, Bernd Gelma, Alice Asinger, Nigel McMan, Christoph J.
* The authors contributed equally
Funding: This study was supported by the Austrian Science Fund (FWF) SFB-54 “InThro”, the Christian Doppler Laboratory for Innovative Treatments in Sepsis, and the FWF’s CCHD (Cellular Communication in Health and Disease).
Christoph Binder was born in 1973 in Vienna, Austria. After studying medicine at the University of Vienna School of Medicine, where he obtained his doctorate in medicine in 1997, he joined the doctoral program at the University of California, San Diego, where he obtained his doctorate in 2002. In 2005, I joined the Department of Laboratory Medicine at the Medical University of Vienna In 2009, he was appointed Professor of Arteriosclerosis Research, and in 2006 I joined CeMM as Principal Investigator. He is a laboratory medicine specialist and leads a research group focusing on the role of immune function in atherosclerosis and how it can be used in therapeutic interventions. For the first time, the protective effect of vaccination against pneumococcus and normal IgM T15 / E06 was described (Binder et al., 2003). His research group discovered that some of the specific oxidation epitopes derived from lipid peroxidation are prime targets for natural antibodies (Chou et al., 2009) and complementary factor H (Weismann et al., 2011). It also defined the protective roles and mechanisms of the balance for IL-5 cytokines (Binder et al. 2004) and IL-13 (Cardilo-Reis et al., 2012), as well as natural IgM antibodies (Gruber et al., 2016); Tsiantoulas et al. , 2017). His recent work focused on the identification and characterization of extracellular vesicles in mitochondria (Puhm et al., C2019). He is the recipient of numerous prestigious fellowships and awards and has authored over 130 publications in popular journals, including Nature Medicine and Nature.
The mission of the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences is to maximize scientific innovation in molecular medicine to improve healthcare. At CeMM, an international and creative team of scientists and clinicians pursue free basic life science research in a large and lively hospital environment of distinct medical traditions and practices CeMM’s research is based on post-genomic technologies and focuses on diseases of social importance, such as immune disorders, infections, cancer, and metabolic disorders. CeMM works in a unique mode of hyper-collaboration, linking biology with medicine, experiments with arithmetic, discovery with translation, science with society and the arts. The aim of CeMM is to pioneer the science that nurtures accurate, personalized, predictive and preventive medicine into the future. CeMM trains a modern mix of biomedical scientists and is located on the campus of the General Hospital and Medical University of Vienna. http: // www.
The Medical University of Vienna (MedUni Vienna) is one of the most traditional medical education and research facilities in Europe. With nearly 8,000 students, it is currently the largest medical training center in German-speaking countries. With 5,500 employees, 30 departments and 2 clinical institutes, 12 centers of medical theory and several highly specialized laboratories, it is also one of the leading research institutions in Europe in the biomedical sector. http: // www.
http: // cemm.