Oxidation-specific epitopes as targets for biotheranostic applications in humans

Abstract

Emerging data demonstrate the potential of translational applications of antibodies directed against oxidation-specific epitopes (OSEs). 'Biotheranostics' as used in this context in cardiovascular disease (CVD) describes targeting of OSEs for biomarker, therapeutic and molecular imaging diagnostic applications. Atherogenesis can be viewed as a chronic, maladaptive inflammatory response to OSE and related antigens. Lipid oxidation collectively yields a large variety of OSE, such as oxidized phospholipids (OxPL) and malondialdehyde epitopes. OSEs are immunogenic, proinflammatory, proatherogenic and plaque destabilizing and represent danger-associated molecular patterns (DAMPs). DAMPs are recognized by the innate immune system via pattern recognition receptors, including scavenger receptors, IgM natural antibodies and complement factor H, which bind, neutralize and/or facilitate their clearance. Biomarker assays measuring OxPL present on apolipoprotein B-100 lipoproteins, and particularly on lipoprotein (a), predict the development of CVD events. In contrast, OxPL on plasminogen facilitate fibrinolysis and may reduce atherothrombosis. Oxidation-specific antibodies attached to magnetic nanoparticles image lipid-rich, oxidation-rich plaques. Infusion or overexpression of oxidation-specific antibodies reduces the progression of atherosclerosis by potentially neutralizing and clearing OSE and preventing foam cell formation, suggesting similar applications in humans. Using the accelerating knowledge base and improved understanding of the interplay of oxidation, inflammation and innate and adaptive immunity in atherogenesis, emerging clinical applications of oxidation-specific antibodies may identify, monitor and treat CVD in humans.