Associate Professor of Medicine
- BA, Tulane University, 1977
- MD, Louisiana State University, 1981
Antiphospholipid autoantibodies are strongly associated with arterial and venous thrombosis, recurrent fetal loss, and thrombocytopenia. These antibodies may occur in patients with systemic lupus erythematosus or related diseases, or as a primary syndrome in the absence of other autoimmune diseases. Antiphospholipid antibodies are typically categorized based on the method used to detect them. Antibodies detected by their ability to prolong certain in vitro coagulation assays are termed lupus anticoagulants; anticardiolipin antibodies are detected in ELISAs in which cardiolipin is the putative antigen. It is hypothesized that these autoantibodies are directly pathogenic by interfering with coagulation reactions that occur on the surface of platelets and/or vascular endothelial cells.
Accordingly, the goal of Dr. Roubey's research is to determine the mechanisms by which antiphospholipid antibodies contribute to thrombosis and recurrent fetal loss. It has previously been though that antiphospholipid autoantibodies are directed against various negatively-charged phospholipids. Over the past several years, however, data from several labs including Dr. Roubey's has challenged this model and suggested that "antiphospholipid" autoantibodies are directed against a number of phospholipid-binding plasma proteins or complexes of these proteins with anionic phospholipid. Potential antigenic targets include b2-glycoprotein I (b2GPI), prothrombin, protein C, and protein S. b2GPI is a normal plasma protein that binds weakly to anionic phospholipids and has anticoagulant activity in a number of in vitro assays. Its physiological role, however, is not known. In patients with the antiphospholipid syndrome, most antibodies detected in anticardiolipin assays are directed against b2GPI; most lupus anticoagulants are antibodies against prothrombin or b2GPI. Antibodies to protein C and protein S, while not detectable by current antiphospholipid antibody assays, may be of significance because of their ability to inhibit the anticoagulant protein C pathway.
Areas of ongoing investigation include the following: characterization of the spectrum of antigenic specificities of "antiphospholipid" antibodies and their respective clinical associations, investigations of the mechanisms of autoantibody-mediated thrombosis in in vitro and in vivo model systems, the effect of antiphospholipid antibodies on the protein C anticoagulant pathway, development of immunoassays using purified protein antigens, and the role of b2GPIin apoptosis.
Dr. Roubey's research team takes advantage of the excellence in thrombosis-related research at the University via collaborations with several members of the UNC Center for Thrombosis and Hemostasis.