Anti-high-density lipoprotein antibodies and lipoprotein characteristics in systemic lupus erythematosus-related cardiovascular disease

Background

The risk of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) is exceedingly high. Previously, a lupus pattern of dyslipidemia has been described (raised triglycerides, and low high-density lipoprotein [HDL]) and we recently reported that these lipid abnormalities were associated with tumor necrosis factor (TNF) activity.

Methods

Twenty-three women (52 ± 8.2 years) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched healthy women (controls). Lipoprotein-related measurements included lipoprotein particle size determination by use of NMR spectroscopy and affinity of low-density lipoprotein (LDL) to proteoglycans. Antibodies against apolipoprotein A1 (apoA1) in HDL and TNF was determined by ELISA. Common carotid intima-media thickness was measured by B-mode ultrasound as a surrogate measure of atherosclerosis.

Results

Anti-apoA1 were raised in SLE cases as compared with SLE controls (P = 0.03) and controls (P = 0.001), and in SLE controls as compared with controls (P = 0.01). Among SLE cases, anti-apoA1 was associated with TNF (P = 0.01). Small dense LDL were more common among SLE controls and controls than in SLE cases (P = 0.036 and 0.086, respectively). Small HDL was more common among controls than in SLE cases and SLE controls (P = 0.001). LDL association with proteoglycans did not differ between groups Activity in the TNF system was significantly associated with triglycerides and negatively with HDL (P < 0.01).

Conclusion

SLE-related dyslipidemia showed a surprising pattern with large LDL and HDL rather than small; that is, not an expected 'atherogenic' lipid profile. Anti-apoA1 antibodies where strongly associated with CVD in SLE. Whether they may play a pathogenic role (e.g. by inhibiting anti-inflammatory properties of HDL) is presently under investigation.