Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations
Article first published online: 7 JAN 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 1, pages 192–200, January 2005
How to Cite
Frostegård, J., Svenungsson, E., Wu, R., Gunnarsson, I., Lundberg, I. E., Klareskog, L., Hörkkö, S. and Witztum, J. L. (2005), Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations. Arthritis & Rheumatism, 52: 192–200. doi: 10.1002/art.20780
- Issue published online: 7 JAN 2005
- Article first published online: 7 JAN 2005
- Manuscript Accepted: 6 OCT 2004
- Manuscript Received: 4 MAY 2004
- King Gustaf V 80th Birthday Fund
- Swedish Society of Medicine
- Swedish Rheumatism Association
- The Torsten and Ragnar Söderberg Foundation
- Swedish Heart-Lung Foundation
- Swedish Science Fund
- Rheuma Research Foundation Margareta
- European Commission
- NIH grants from SCOR. Grant Numbers: HL-64833, HL-56989
Cardiovascular disease with premature atherosclerosis is common in patients with systemic lupus erythematosus (SLE). We previously identified elevated levels of oxidized low-density lipoprotein (OxLDL) together with elevated levels of autoantibodies related to OxLDL as risk factors for cardiovascular disease in female patients with SLE. Autoantibodies to OxLDL are common in SLE and cross-react with anticardiolipin antibodies (aCL). We therefore hypothesized that lipid peroxidation is enhanced in patients with SLE in general.
One hundred forty-seven female patients with SLE and 60 age- and sex-matched controls were compared. A monoclonal antibody to oxidized phospholipids, EO6, was used to determine oxidation epitopes on LDL. Anti-OxLDL and autoantibodies to malondialdehyde (MDA)–modified LDL, cardiolipin, and oxidized aCL were determined by chemiluminescence technique.
As determined by binding of EO6, patients with SLE had a higher level of oxidized phospholipids on LDL (P = 0.005) compared with controls. The level of OxLDL (e.g., oxidized phospholipid/apolipoprotein B) was associated with arterial disease (P = 0.006) and renal manifestations (P = 0.04). As reported previously, levels of aCL, autoantibodies to OxLDL, and autoantibodies to MDA-modified LDL were enhanced and were closely correlated in SLE. Anticardiolipin antibodies from these SLE patients recognized mainly oxidized forms of cardiolipin, indicating that antigenic epitopes on cardiolipin are related to lipid peroxidation in patients with SLE.
In general, patients with SLE (particularly those with cardiovascular disease) had more oxidized epitopes on LDL compared with controls. Furthermore, aCL in these patients recognized epitopes generated during lipid peroxidation. Thus, “neo” self antigens on lipoproteins, generated during oxidation, are present in SLE and may be of importance for the development of premature cardiovascular disease and possibly also for other autoimmune phenomena observed in SLE.