Atherosclerosis and APS 79 Clinical Reviews in Allergy & Immunology Volume 25, 2003 79 *Author to whom all correspondence and reprint requests should be addressed. E-mail: shoenfel@post.tau.ac.il Clinical Reviews in Allergy and Immunology © Copyright 2003 by Humana Press Inc. 1080-0549/03/79–88/$20.00 Index Entries: Abstract Atherosclerosis is an autoimmune/inflammatory disease associated with infectious, inflam- matory, 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 β2-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 ani- mals. 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 β-2 Gly- coprotein (anti-β2-GPL), anti-prothrombin antibodies, may play a role in premature athero- sclerosis 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 oxi- dation of LDL, thereby accounting for the antioxidant properties and the atherosclerotic pro- tective effects of HDL. The relationship between PON1 and aPL has been recently suggested. IgG anti-HDL and IgG anti-β2-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 meth- ods 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. Atherosclerosis and Antiphospholipid Syndrome Luis J. Jara, 1 Gabriela Medina, 2 Olga Vera-Lastra, 3 and Yehuda Shoenfeld *,4 1 Clinical Research Unit and Rheumatology Department, Hospital de Especialidades Centro Medico La Raza, 2 Internal Medicine Department, Hospital General N° 76, 3 Internal Medicine Department, Hospital de Especialidades Centro Medico La Raza, IMSS, Mexico City, México, 4 Department of Medicine B, and Centre of Autoimmune Diseases, Sheba Medical Center, Israel Atherosclerosis; autoimmunity; inflammation; antiphospholipid antibodies; heat shock proteins; oxLDL; β2–GPI.