Accelerated atherosclerosis in patients with SLE—mechanisms and management

Abstract

Rapid-onset cardiovascular disease is a major concern for many patients suffering from SLE. Cardiovascular events are more frequent and occur much earlier in SLE patients compared to healthy controls. Traditional risk factors such as altered lipid levels, older age and smoking do not fully explain the increased risk of cardiovascular disease, strongly suggesting that autoimmunity contributes to accelerated atherosclerosis. Altered immune system function is recognized as the primary contributor to both the initiation and progression of atherosclerosis. Multiple manifestations of autoimmunity, including autoantibodies, altered cytokine levels and innate immunity response, adipokines, dysfunctional lipids, and oxidative stress appear to contribute to atherosclerotic risk. In addition, multiple SLE therapeutics appear to affect the development and progression of atherosclerosis both positively and negatively. SLE-specific biomarkers for identifying patients at risk of developing accelerated atherosclerosis are starting to be identified by multiple groups, and a comprehensive, clinically testable biomarker panel could be invaluable for identifying and treating these patients.

Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency

“…This is particularly interesting considering that SLE patients display premature atherosclerosis and are at high risk for cardiovascular disease complications, which cannot be explained by the traditional risk factors. 33 Thus, our data suggest that anti-IgE treatment could be considered as a therapeutic option for accelerated atherosclerosis in autoimmune diseases. sIgM -/-were fed an atherogenic diet for 6 or 8 weeks respectively.…”

Identification of Cerebral Infarction-Specific Antibody Markers from Autoantibodies Detected in Patients with Systemic Lupus Erythematosus

“…Available data suggest that young women with SLE are at a substantially increased risk of AMI, congestive heart failure, and cerebrovascular accidents [12][13][14]. If autoantibodies develop during the progress of CI and CVD, they can be amplified in patients with SLE due to their dysregulated immune systems.…”

“…Accelerated atherosclerotic diseases have been recognized as major causes of mortality in SLE. In the study of large case series of patients with SLE, 6-20% and 4-15% of deaths were due to cardiovascular disease (CVD) and cerebrovascular disease, respectively [12][13][14]. To estimate the onset risk of accelerated atherosclerosis in SLE patients, several markers have been introduced including C-reactive protein [15], lipoprotein (a) [16], homocysteine [17], inflammatory cytokines [18,19], yet the satisfactory results have not been obtained.…”

Targeting B Cells in Atherosclerosis

“…For example, patients with SLE have been found to develop autoantibodies against ApoAI, which have been associated with acute coronary syndromes. 9 The development of B-cell-targeting therapeutics for RA and SLE has gained a lot of attention in the past years. The first B-cell therapeutic agent that has been approved for clinical use in patients with RA is the anti-CD20 antibody (rituximab).…”

“…There are also other autoantigens involved, such as heat shock protein 60,6,7 and the impact of other autoimmune diseases in promoting atherosclerosis such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is well known. 8,9 The role of T cells and interferon-γ-secreting Th1 cells, in particular, as key drivers of plaque inflammation is well documented, and experimental approaches to dampen these responses by enhancing the activity of regulatory T cells are being tested. More recently, it was found that B cells could…”