Macrophage activation and coronary atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis

Rho, Young Hee; Solus, Joseph F.; Raggi, Paolo; Oeser, Annette; Gebretsadik, Tebeb; Shintani, Ayumi; Stein, C. Michael

doi:10.1002/acr.20365

Cited by 48 publications

(44 citation statements)

References 39 publications

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“…This indicates that CVD in rheumatoid arthritis is associated with enhanced mononuclear-(neopterin, CCL2) and B-cell activation (CXCL13), and as a consequence increased immune activity. Rho et al found higher neopterin concentrations in RA and systemic lupus erythematosus compared to healthy controls associated with erythrocyte sedimentation rate but not associated with coronary atherosclerosis in either disease (24). Patients with CVD show elevated levels of several inflammatory mediators -in particular elevated neopterin concentrations have been reported in patients with various cardiovascular diseases like coronary disease, reviewed by Fuchs et al (13), coronary and peripheral artery disease (12).…”

Section: Resultsmentioning

confidence: 99%

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Fagerer

Arnold²,

Bernatzky

et al. 2011

Pteridines

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In chronic inflammatory processes like rheumatoid arthritis (RA) and cardiovascular diseases (CVD) the role of pteridines and chemokines in the immune response is of great interest. The objectives of the study were to obtain information about an involvement of specific chemokines on the inflammatory process in patients with RA and CVD with activated production of the pteridine neopterin. 113 patients with RA according to American College of Rheumatology criteria including 24.8% suffering from CVD were included in the study (23% male, 77% female). For the assessment of monocyte activation and chemotaxis as well as the proinflammatory influence of chemokines on B-cells and angiogenesis in RA, neopterin and the chemokines CCL2, CXCL13 and CX3CL1 were measured by radio-and enzyme-immunoassays in serum. Neopterin and chemokines were all found in high concentrations. Neopterin significantly correlated with all chemokines: CXCL13 (r s = 0.368; p <0.0001), CX3CL1 (r s = 0.241; p <0.02), CCL2 (r s = 231; p <0.02), demonstrating high neopterin levels in RA patients to have a strong association to the chemokine induced chemotaxis of B-cells (CXCL13) and mononuclear cells (CX3CL1, CCL2). Significantly elevated concentrations of neopterin and CXCL13 were seen in patients with RA plus CVD compared to RA without CVD (p <0.03). The high incidence of cardiovascular diseases in rheumatoid arthritis seems to be associated with enhanced mononuclear (neopterin, CCL2) and B-cell activation (CXCL13), and as a consequence increased immune system activity.

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Section: Resultsmentioning

confidence: 99%

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Fagerer

Arnold²,

Bernatzky

et al. 2011

Pteridines

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“…16–19 Serum concentrations of TNFα and IL-6 were measured by multiplex ELISA (Millipore) in study participants (117 SLE, 164 RA and 172 controls).…”

Section: Methodsmentioning

confidence: 99%

Genetics of serum concentration of IL-6 and TNFα in systemic lupus erythematosus and rheumatoid arthritis: a candidate gene analysis

et al. 2015

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Elevated concentrations of inflammatory mediators are characteristic of autoimmune disease accompanied by chronic or recurrent inflammation. We examined the hypothesis that mediators of inflammation known to be elevated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with genetic polymorphism previously identified in studies of inflammatory disease. Serum interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα concentrations in patients with SLE (n=117) or RA (n=164) and in inflammatory disease-free control subjects (n=172) were measured by multiplex ELISA. Candidate genes were chosen from studies of autoimmune and inflammatory disease. Genotypes were determined for 345 SNP markers in 75 genes. Association between serum analytes and single alleles was tested by linear regression. Polymorphisms in several genes were associated with IL-6 levels (including IL10, TYK2 and CD40L in SLE and DRB1, NOD2 and CSF1 in RA) or with TNFα levels (including TNFSF4 and CSF2 in SLE and PTPN2, DRB1 and NOD2 in RA). Some associations were shared between disease and control groups or between IL-6 and TNFα within a group. In conclusion, variation in genes implicated in disease pathology is associated with serum IL-6 or TNFα concentration. Some genetic associations are more apparent in healthy controls than in SLE or RA, suggesting dysregulation of the principal mediators of chronic inflammation in disease. Susceptibility genes may affect inflammatory response with variable effect on disease etiology.

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“…Monocyte activation is globally higher in SLE, but monocyte activation does not correlate with increased coronary atherosclerosis 15 (Figure 1). …”

Section: Pathogenesis Of Atherosclerosis In Slementioning

confidence: 99%

Accelerated atherosclerosis in patients with SLE—mechanisms and management

2012

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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.

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Macrophage activation and coronary atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis

Cited by 48 publications

References 39 publications

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Genetics of serum concentration of IL-6 and TNFα in systemic lupus erythematosus and rheumatoid arthritis: a candidate gene analysis

Accelerated atherosclerosis in patients with SLE—mechanisms and management

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