Immunomodulation for accelerated atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus

Abstract

In the last decades, consisting evidence supported a close relationship between both innate and adaptive immune systems and the accelerated cardiovascular (CV) disease characterizing autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Indeed, several cell lines involved in the pathogenesis of these autoimmune diseases, such as macrophages and dendritic cells, as well as different T and B lymphocyte subsets, and inflammatory cytokines, have been demonstrated to be directly involved in the mechanisms underlying early atherosclerotic arterial wall damage. Traditional CV risk factors play a concomitant role but do not sufficiently account for the increased prevalence of CV disease in these patients. Indeed, the pathophysiological link between RA and SLE and atherosclerosis is based on complex inflammatory pathways that interconnect these conditions and may explain the significant morbidity and mortality rates demonstrated in these patients, with consequent significant negative effects on quality of life and long-term survival. Consequently, it is intriguing to hypothesize that immunosuppressive drugs commonly used in the treatment of these pathologies may also exert an immunomodulatory and anti-inflammatory effect in mitigating the atherosclerotic damage that has been demonstrated to occur early in the initial stages of the disease. Recognizing risk factors, predicting occurrences and early intervention to prevent CV disease development have emerged as critical objectives in RA and SLE treatment. In this review, we aimed to provide an updated overview of the atherogenic effects exerted by the immune and inflammatory pathways involved in the pathogenesis of RA and SLE. Moreover, we examined the available evidence which may support the potential effects of immunosuppressive therapies in reducing CV damage and, consequently, CV disease risk in these patients.

Keywords: Adaptive immunity; Atherosclerosis; Autoimmune diseases; Cardiovascular diseases; Innate immunity.