Newly published research funded by the LRI has identified the exact cell autoantibodies target to cause dangerous blood clots in people with lupus.
Led by Dr. Bruce Furie of Beth Israel Deaconess Medical Center and Harvard Medical School, the findings provide researchers with insight on how to develop safer and more specific treatments to stop clotting in lupus. In addition, the findings may be applicable to anyone who suffers from the autoimmune clotting disorder known as antiphospholipid syndrome (APS) – with or without lupus.
Why does clotting go awry?
Platelets are blood cells that are the first responders to an injury. When someone gets a cut, platelets arrive at the scene and help form a clot to stop the bleeding.
A person with lupus is at risk for APS, a potentially life-threatening complication where the body makes antibodies that interact with blood cells to trigger blood clots when there is no injury. These clots can cause strokes, heart attacks and other dangerous conditions. APS also has a significant impact on the health and safety of pregnant women because these antibodies can cause miscarriages and pre-eclampsia (high blood pressure during pregnancy).
Previous research identified autoantibodies that attach to a protein called beta2-glycoprotein-1 as a biomarker for predicting and monitoring APS. Beta2-glycoprotein-1 circulates through the bloodstream and when the autoantibodies come into contact with it they fuse together into a complex that mistakenly triggers clotting. Until this recent discovery the exact kind of cell the complex acts on to promote clotting was a mystery..
Hitting the Bullseye
Accurately identifying the target of the beta2-glycoprotein-1 autoantibody complex was challenging. Researchers have thought that the autoantibodies could be activating any of the different types of cells integral to the clotting process.
With his 2013 LRI Novel Research Grant, Dr. Furie used cutting-edge imaging techniques in live mice to show that it is the beta2-glycoprotein-1 autoantibody complex that activates platelets to form clots. Dr. Furie’s study also showed that when platelets are not switched on, clotting stopped even in the presence of APS autoantibodies.
Treatment options for people with lupus and APS are limited. If we can understand the pathway by which APS antibodies cause harm, therapies can be developed to block these mechanisms. The ultimate goal is an oral medication that prevents these deadly blood clots.
Building on the new discovery described here, Dr. Furie’s next step is to narrow down what the autoandibody complexes are attaching to on the platelet. Once the receptor on platelets is located and characterized, researchers may be able to create targeted treatments that stop the autoantibody complexes from attaching to platelets to trigger clotting.