Inflammatory expression profiles in monocyte-to-macrophage differentiation in patients with systemic lupus erythematosus and relationship with atherosclerosis.

INTRODUCTION: Our objectives were to examine mononuclear cell gene expression profiles in patients with systemic lupus erythematosus (SLE) and healthy controls and to compare subsets with and without atherosclerosis to determine which genes' expression is related to atherosclerosis in SLE. METHODS: Monocytes were obtained from 20 patients with SLE and 16 healthy controls and were in vitro-differentiated into macrophages. Subjects also underwent laboratory and imaging studies to evaluate for subclinical atherosclerosis. Whole-genome RNA expression microarray was performed, and gene expression was examined. RESULTS: Gene expression profiling was used to identify gene signatures that differentiated patients from controls and individuals with and without atherosclerosis. In monocytes, 9 out of 20 patients with SLE had an interferon-inducible signature compared with 2 out of 16 controls. By looking at gene expression during monocyte-to-macrophage differentiation, we identified pathways which were differentially regulated between SLE and controls and identified signatures based on relevant intracellular signaling molecules which could differentiate SLE patients with atherosclerosis from controls. Among patients with SLE, we used a previously defined 344-gene atherosclerosis signature in monocyte-to-macrophage differentiation to identify patient subgroups with and without atherosclerosis. Interestingly, this signature further classified patients on the basis of the presence of SLE disease activity and cardiovascular risk factors. CONCLUSIONS: Many genes were differentially regulated during monocyte-to-macrophage differentiation in SLE patients compared with controls. The expression of these genes in mononuclear cells is important in the pathogenesis of SLE, and molecular profiling using gene expression can help stratify SLE patients who may be at risk for development of atherosclerosis.

Telomere length in patients with systemic lupus erythematosus and its associations with carotid plaque.

OBJECTIVE: To evaluate telomere length (TL) between patients with SLE and healthy controls and to test if TL is associated with carotid plaque. METHODS: A pilot study of 154 patients with SLE and 152 controls was performed from the SOLVABLE (Study of Lupus Vascular and Bone Long-Term Endpoints) cohort. Demographic and cardiovascular disease (CVD) factors were collected at baseline. The presence or absence of plaque was evaluated by B-mode US. Genomic DNA was isolated from whole peripheral blood. TL was quantified using real-time quantitative PCR. RESULTS: SLE women had a short TL compared with healthy controls (4.57 vs 5.44 kb, P = 0.03). SLE women showed shorter TL than controls across all age groups: <35 years (4.38 vs 6.37 kb), 35-44 years (4.52 vs 5.30 kb), 45-54 years (4.77 vs 5.68 kb) and ≥55 years (4.60 vs 4.71 kb). Among patients with SLE and carotid plaque there was a trend towards shorter TL at a younger age and it was significantly lower in the 35- to 44-year age group when compared with controls (P = 0.025). Multiple logistic regression analysis indicated a risk of carotid plaque with older age [odds ratio (OR) 1.09; 95% CI 1.06, 1.12] but not with TL (OR 1.05; 95% CI 0.97, 1.13). CONCLUSION: SLE women had significantly shorter TL than controls. SLE women trended towards shorter TL at a younger age. When carotid plaque was identified, the younger SLE women had shorter TL. Only older age but not shorter TL was independently associated with carotid plaque. Additional studies are needed to confirm if TL is a novel biomarker for cardiovascular disease in SLE.

Management of cardiovascular complications in systemic lupus erythematosus.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Patients with SLE have an excess risk compared with the general population; this is particularly pronounced in younger women with SLE who have an excess risk of over 50-fold compared with population controls. There is a higher prevalence of subclinical atherosclerosis in patients with SLE compared with controls, as demonstrated by a variety of imaging modalities discussed in this review. The causality of the excess risk of CVD and subclinical atherosclerosis is multifactorial in patients with SLE. While traditional risk factors play a role, after controlling for the traditional Framingham risk factors, the excess risk is still 7.5-fold greater than the general population. This review will also cover novel cardiovascular risk factors and some SLE-specific variables that contribute to CVD risk. This review discusses the risk factor modification and the evidence available for treatment of these risk factors in SLE. There have not yet been any published randomized, controlled trials in patients with SLE with respect to CVD risk factor modifications. Thus, the treatment and management recommendations are based largely on published guidelines for other populations at high risk for CVD.