THU0236 Antibodies towards atp-binding cassette transporter abca1: a new mechanism for atherosclerosis in sle?

Background Systemic Lupus Erythematosus (SLE) is considered an independent risk factor for cardiovascular disease and patients with SLE have an increased burden of atherosclerotic vascular disease1. High-density lipoproteins (HDL) are the plasma lipoproteins responsible for reverse cholesterol transport2. HDL protective effect on cardiovascular disease is attributed to the cholesterol efflux capacity as well as to its anti-oxidant and anti-inflammatory properties3. Dyslipidemia is frequent amongst patients with SLE, characteristically with low HDL levels. ATP-binding cassette transporter ABCA1, also known as the cholesterol efflux regulator protein, is a ubiquitous cholesterol transporter that is highly expressed in macrophages. Its main function is to donate cholesterol to apolipoprotein A-I (ApoA-I) in lipid-poor HDL particles. As such, ABCA1 closely influences HDL levels and its role in atherosclerosis has been increasingly studied4. Objectives This study was undertaken to determine if antibodies against ABCA1 can be detected in patients with SLE through enzyme-linked immunosorbent assay (ELISA). Methods Patients with SLE were divided in two groups: group A, with low damage (based on less than 4 SLICC criteria), and group B, with high damage (based on the presence of at least 4 SLICC criteria). Groups A and B were compared with a control group. 48 patients were enrolled (13 in group A and 35 in group B), and 18 age and gender-matched healthy controls were included in the control group. IgG anti-ABCA1 and anti-HDL antibodies were assessed by home-made ELISAs, using commercially available ABCA1 synthetic peptide and HDL from healthy donors. Results There were no differences between group A and the control group. Group B had higher titers of anti-ABCA1 antibodies when compared with group A (p=0.016) and the control group (p=0.022). For positivity we considered values superior to 3 standard deviations above the mean of healthy controls. Four patients showed positive anti-ABCA1 titers (11.4%). Conclusions This is the first time that naturally occurring antibodies against ABCA1 are detected by ELISA. These antibodies are increased in patients with SLE that have higher damage, measured by SLICC classification criteria. Future studies will determine their pathogenic role and the potential use of a standardized ELISA to detect anti-ABCA1 antibodies in clinical practice. References Stojan G, Petri M. Atherosclerosis in systemic lupus erythematosus. J Cardiovasc Pharmacol. 2013; 62(3):255–262. Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res. 2005;96:1221–1232. Navab M, Yu R, Gharavi N, et al. High-density lipoprotein: antioxidant and anti-inflammatory properties. Curr Atheroscler Rep. 2007;9(3):244–8. Soumian S, Albrecht C, Davies AH, Gibbs RGJ. ABCA1 and atherosclerosis. Vasc Med. 2005; 10:109–119. Disclosure of Interest None declared