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Trigger for autoimmune disease APS discovered

The autoimmune disease APS can lead to complications in pregnant women. Researchers have now discovered the trigger for APS. | © evgenyatamanenko - stock.adobe.com

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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 University Medical Center Mainz, has uncovered the mechanism that triggers the autoimmune disease APS (antiphospholipid syndrome). APS is a previously unknown interaction between the immune system and the blood coagulation system. It causes thrombosis and pregnancy complications in affected individuals. The discovery raises hope for a novel therapeutic approach for APS, which could be observed in the mouse model.

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The APS-inducing mechanism has not been adequately understood. "Over the past 30 years, various factors in disease development have been discussed. Their interaction was held responsible for the thrombosis tendency and pregnancy complications in APS," reports Prof. Wolfram Ruf. "In contrast, we have now been able to show that the binding of antiphospholipid antibodies primarily causes all the disease-causing effects of APS to a single target structure in the blood vessels," Ruf said. 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. In turn, B lymphocytes proliferate, producing 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 Medical Center 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 defensive substances (antibodies) against the body's own components. In APS, the eponymous antiphospholipid antibodies are produced. They are directed against components on blood cells and vessel wall cells. This leads to an increased tendency of the blood to clot. This can have serious consequences for those affected: People with APS are prone to blood clots (thromboses), leading to complications such as stroke, heart attack or pulmonary embolism. In the event of pregnancy, the risk of miscarriage is significantly increased in affected women.

Observations in the animal model give hope for a therapeutic approach

"With our study, we have not only uncovered the trigger of the immune disease but have furthermore 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. The CTH scientists succeeded in identifying an antibody that can be used to block the protein-lipid complex in a way that prevents the effects of the antiphospholipid antibodies. As a result, the autoimmune reaction was absent in a mouse model.

Original publication: N. Müller-Calleja, A. Hollerbach, J. Royce, S. Ritter, D. Pedrosa, T. Madhusudhan, S. Teifel, M. Meineck, F. Häuser, A. Canisius, T. Son Nguyen, J.Braun, K. Bruns, A. Etzold, U. Zechner, S. Strand, 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), University Medicine Mainz, ruf(at)uni-mainz.de

Source: Press release University Medicine Mainz