PEPTIDE-BASED THERAPY FOR ANTIPHOSPHOLIPID SYNDROME: ISOLATION AND CHARACTERIZATION OF PEPTIDES THAT INHIBIT THE ACTIVITY OF ANTI-B2GPI ANTIBODIES

Antiphospholipid syndrome (APS) is an autoimmune disorder originally defined by the presence of distinct clinical features and autoantibodies against phospholipids. Clinically, the disease is characterized by excessive clotting events (Hypercoagulability) in both the arterial and venous systems. In women, complications of the disease include recurrent miscarriages presence of characteristic antibodies. The disease can strike any part of the body. The disease can be mild, but it can worsen and develop into Catastrophic Antiphospholipid Syndrome. In this situation there is a storm of coagulation and mortality is about 50%.

These antibodies are Anticardiolipin, Lupus Anticoagulant and Beta 2 glycoprotein I.

While several types of autoantibodies have been described in APS, it has been shown that Antiphospholipid antibodies do not react directly with phospholipids but rather with a serum protein β2- glycoprotein (Β2GPI), only when it is bound to cell membrane. This binding activates the coagulation system resulting in thrombosis in the placenta and complications of pregnancy and menopause. Premature birth occurs in about 70% of all women patients with the disease. Treatment of the disease is essentially giving anticoagulants (warfarin, heparin its various forms) and anti-platelet Igor (especially aspirin). There is medication for the disease, but with side effects and other problems so it is necessary to develop a novel and safe drug.

Our aim in this project was to isolate peptides that would inhibit the binding of anti-B2GPI antibodies to phospholipid-bound B2GPI. Using phage display libraries we isolated several such peptides. The system used to isolate and characterize these peptides will be presented as the planned translational use of these peptides discussed.