Elevated triglycerides and low levels of high-density lipoprotein as markers of disease activity in association with up-regulation of the tumor necrosis factor α/tumor necrosis factor receptor system in systemic lupus erythematosus

Objective. To investigate how blood lipid levels are related to disease activity, clinical characteristics, and serum levels of tumor necrosis factor alpha (TNFalpha) and its soluble type 1 and 2 receptors, sTNFR1 and sTNFR2, in systemic lupus erythematosus (SLE). Methods. Fasting blood samples were obtained from an unselected cohort of SLE patients at Karolinska Hospital (n = 208, mean +/- SD age 45.7 +/- 14.2 years). Disease activity was estimated using the SLE Disease Activity Measure (SLAM). Levels of circulating TNFalpha, sTNFR1, and sTNFR2 were determined by enzyme-linked immunosorbent assay. Blood lipid levels obtained after overnight fasting were analyzed by routine chemistry. Results. Triglyceride (TG) levels were associated with the SLAM score (r = 0.48, P < 0.0001) and with the activities of TNFalpha (r = 0.29, P = 0.0001), sTNFR1 (r = 0.38, P < 0.0001), and sTNFR2 (r = 0.40, P < 0.0001). High-density lipoprotein (HDL) levels were negatively associated with the SLAM score (r = -0.27, P = 0.0003) and with the activities of TNFa (r = -0.15, P = 0.04) and sTNFR2 (r = -0.19, P = 0.01). High levels of TGs, total cholesterol, TNFalpha, sTNFR1, and sTNFR2 all showed close correlations with the presence of nephritis and arterial disease (P < 0.05). In multiple logistic regression models, the TNFalpha activity and TG levels were independent determinants (P = 0.003 for both) of active disease (SLAM score greater than or equal to7). Conclusion. Dyslipoproteinemia with high TG/low HDL levels correlates with disease activity in SLE, and enhanced activity in the TNFalpha/sTNFR system seems to be an important underlying factor. Both dyslipoproteinemia and enhanced activity of the TNFalpha system are closely related to cardiovascular and renal manifestations in SLE, and thus both may serve as markers of more severe disease.