A team of researchers led by prof. Wolfram ruf, principal investigator at the DZHK and scientific director of the center for thrombosis and hemostasis (CTH) at the universitatsmedizin mainz, has uncovered the mechanism that triggers the autoimmune disease APS (antiphospholipid syndrome): a previously unknown interaction between the immune system and the blood clotting system. This causes thrombosis and pregnancy complications in those affected. The discovery raises hopes for a novel therapeutic approach to APS that could be observed in the mouse model.
The APS-triggering mechanism has not yet been sufficiently clarified. "over the past 30 years, various factors in the pathogenesis of the disease have been discussed. Their interaction has been held responsible for the thrombosis tendency and pregnancy complications in APS," reports prof. Wolfram ruf. "We have now been able to show that all the disease-causing effects of APS are primarily caused by the binding of antiphospholipid antibodies to a single target structure in the blood vessels," says ruf. The target structure is a protein-lipid complex, the so-called EPCR-LBPA complex: when the antiphospholipid antibodies bind to it, this activates complex cellular processes that lead to increased blood coagulation and the production of the messenger substance interferon-α. This in turn causes B-lymphocytes to proliferate and produce new antiphospholipid antibodies. In this way, the autoimmune reaction continues to intensify. The mechanism was discovered by a team of researchers from the Center for Thrombosis and Hemostasis (CTH), other institutes of the University of Mainz and colleagues from the USA.
Stroke, heart attack or pulmonary embolism as a result of APS
Antiphospholipid syndrome (APS) is an autoimmune disease in which the immune system mistakenly produces antibodies against the body’s own components. In APS, the eponymous antiphospholipid antibodies are produced. They target components on blood cells and vessel wall cells. This results in an increased tendency of the blood to clot. People with APS are prone to blood clots (thromboses), which can lead to complications such as stroke, heart attack or pulmonary embolism. In the event of pregnancy, affected women are at significantly increased risk for miscarriage.
Observations in animal models give hope for therapeutic approach
"with our study, we have not only uncovered the trigger of the immune disease, but have also shown in an animal model that a new therapeutic approach could prevent the development of the disease and the associated tendency to thrombosis and pregnancy complications," explains ruf. cth scientists succeeded in identifying an antibody that can block the protein-lipid complex in a way that prevents the effects of antiphospholipid antibodies. As a result, the autoimmune reaction did not occur in a mouse model.
Original publication: N. Muller-calleja, A. Hollerbach, J. Royce, S. Knight, D. Pedrosa, T. Madhusudhan, S. Teifel, M. Meineck, F. Houses, A. Canisius, T. Son nguyen, J.Brown, K. Bruns, A. Etzold, U. Zechner, S. Beach, M. Radsak, D. Strand, J-M. Gu, J. Weinmann-menke, C. T. Esmon, L. Teyton, K. J. Lackner, W. Ruf. Lipid presentation by the protein C receptor links coagulation with autoimmunity. Science. 2021 mar 12;371(6534):eabc0956. DOI: 10.1126/science.Abc0956
Scientific contact: univ.-prof. Dr. Wolfram ruf, scientific director of the center for thrombosis and hemostasis (CTH), universitatsmedizin mainz, ruf(at)uni-mainz.De
Further press releases and news
Surprising results on mortality from thrombosis and pulmonary embolism
Fewer deaths from pulmonary embolism, but more younger people dying from thrombosis: a surprising finding from an analysis of World Health Organization (WHO) data. The analysis applies to the entire population of Canada and the U.S. in the.
