ARTHRITIS & RHEUMATISM Vol. 62, No. 3, March 2010, pp 845–854 DOI 10.1002/art.27286 © 2010, American College of Rheumatology Antibodies to Apolipoprotein A-I, High-Density Lipoprotein, and C-Reactive Protein Are Associated With Disease Activity in Patients With Systemic Lupus Erythematosus Sean G. O’Neill, 1 Ian Giles, 2 Anastasia Lambrianides, 2 Jessica Manson, 2 David D’Cruz, 3 Leslie Schrieber, 4 Lyn M. March, 4 David S. Latchman, 2 David A. Isenberg, 2 and Anisur Rahman 2 Objective. Inflammatory disease activity in pa- tients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti–apolipoprotein A-I (anti–Apo A-I), anti–high-density lipoprotein (anti- HDL), and anti–C-reactive protein (anti-CRP) auto- antibodies. We undertook this study to examine whether levels of these antibodies rise in association with in- creased SLE disease activity. Methods. IgG anti–Apo A-I, anti-HDL, and anti- CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activ- ity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus ne- phritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. Results. Serum levels of IgG anti–Apo A-I, anti- HDL, and anti-CRP were higher in patients with SLE than in controls. Anti–Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with per- sistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti–Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti–Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti–double-stranded DNA. Conclusion. Persistent disease activity is associ- ated with a significant increase in IgG anti–Apo A-I and anti-HDL in patients with SLE. The development of cardiovascular disease (CVD), particularly coronary artery disease (CAD) and stroke, is an important clinical problem in patients with Dr. O’Neill’s work was supported by LUPUS UK and the National Health and Medical Research Council, Australia (scholarship 512038). Drs. Giles and Lambrianides’ work was funded by the Wellcome Trust and the Rosetrees Foundation, UK. Ms Manson is recipient of a Clinical Research Fellowship from the Arthritis Re- search Campaign, UK. 1 Sean G. O’Neill, BMed, FRACP: University College Lon- don, London, UK, University of Sydney, Sydney, New South Wales, Australia, and Royal North Shore Hospital, St. Leonards, New South Wales, Australia; 2 Ian Giles, PhD, MRCP, Anastasia Lambrianides, PhD, Jessica Manson, MBChB, MRCP, David S. Latchman, PhD, DSc, FRCPath, FRSA, David A. Isenberg, MD, FRCP, Anisur Rah- man, PhD, FRCP: University College London, London, UK; 3 David D’Cruz, MD, FRCP: St. Thomas’ Hospital, London, UK; 4 Leslie Schrieber, MBBS (Hons), MD, FRACP, Lyn M. March, MD, PhD, FRACP: University of Sydney, Sydney, New South Wales, Australia, and Royal North Shore Hospital, St. Leonards, New South Wales, Australia. Dr. Schrieber has received consulting fees, speaking fees, and/or honoraria from Sanofi-Aventis and Wyeth, Australia (less than $10,000 each). Dr. March has received speaking fees from Schering- Plough (less than $10,000) and serves on the Schering-Plough medical advisory board. Address correspondence and reprint requests to Sean G. O’Neill, BMed, FRACP, Kolling Institute, Royal North Shore Hospi- tal, St. Leonards, Sydney, NSW 2065, Australia. E-mail: soneill@ med.usyd.edu.au. Submitted for publication March 13, 2009; accepted in revised form November 25, 2009. 845