Atherosclerosis and antiphospholipid syndrome

Atherosclerosis is an autoimmune/inflammatory disease associated with infectious, inflammatory, and autoimmune factors. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and/or progression of atheromatous lesions. Heat-shock protein (hsp), oxidized low-density lipoprotein (LDL), and beta2-GPI have been reported to elicit humoral and cellular immune response in both experimental animals and humans. These autoantigens are expressed within atherosclerotic lesions. Immunization with the given autoantigens elicits an immune response that influences lesion progression. Atherosclerosis susceptibility can be transferred by autoantigen-sensitized lymphocytes from immunized animals. Patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) have a high risk for atherosclerotic cardiovascular events. The traditional risk factors fail to fully account for accelerated atherosclerosis in SLE and APS. Immunological alterations, such as antibodies to oxidized LDL, antiphospholipid antibodies (aPL), antibodies to beta-2 Glycoprotein (anti-beta2-GPL), anti-prothrombin antibodies, may play a role in premature atherosclerosis in SLE and APS. Paraoxonase (PON1) is an enzyme with antioxidant activity attached to the circulating high-density lipoprotein (HDL) in plasma. Its function is to prevent oxidation of LDL, thereby accounting for the antioxidant properties and the atherosclerotic protective effects of HDL. The relationship between PON1 and aPL has been recently suggested. IgG anti-HDL and IgG anti-beta2-GPI antibodies were associated with reduced PON1 activity in patients with SLE and primary APS. The determination of classic and new factors, together with specific autoantibody titers and the use of Doppler carotid ultrasound, are useful methods to detect early atherosclerosis in SLE and PAPS. Therapeutic strategies, including early control of disease and other risk factors, are essential to reduce morbidity and mortality.