It is clinically relevant to develop novel therapies to modulate the autoimmune responses driving atherosclerosis. Patients suffering from systemic lupus erythematosus (SLE) are at  increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. Subjects with SLE and matched healthy controls had similar levels of oxidized LDL in plasma but the correlation with IL-6 was stronger in SLE subjects (r=0.32, p<0.05. We assess two immunomodulatory approaches to target the oxidized LDL autoantigen that contributes to accelerated atherosclerosis in SLE with a  hypercholesterolemic SLE mouse model (B6.lpr.ApoE-/- mice), similar to the premature atherosclerosis observed in SLE patients. Firstly, mucosal tolerance induction with a fusion protein between apolipoprotein B-100 peptide p45 (amino acids 661-680) and cholera toxin B-subunit increased regulatory T cells and B cells in mesenteric lymph nodes and reduced plaque development in the aorta by 33%. Secondly, an antibody treatment with a MDA-p45 specific IgG, binding to the inhibitory Fcreceptor IIB, reduced aortic atherosclerosis by 43%, subvalvular plaque area by 50% and the macrophage content by 31%. Additionally, the antibody removed circulating oxLDL successfully, suggesting an induction in systemic clearance of the autoantigen. The present study provides experimental and clinical support for oxLDL as a possible target for prevention of cardiovascular complications in SLE.

03 - IMMUNOMODULATION WITH AN APOB-100 PEPTIDE VACCINE ELICITS A PROTECTIVE RESPONSE BY INHIBITING ATHEROSCLEROTIC PROGRESSION IN MURINE SYSTEMIC LUPUS ERYTHEMATOUS WITH HYPOERCHOLESTEROLEMIA