Influence of autoimmunity and inflammation on endothelial function and thrombosis in systemic lupus erythematosus patients

Abstract

The aim of this study is to assess the relationship between autoimmunity and endothelial activation/damage (ICAM-1 and vWF serum levels) and the degree of prothrombotic activity (thrombin-antithrombin complexes-TAT serum levels) in SLE. In 60 clinically stable SLE patients, levels of the following parameters were estimated in their serum: lupus anticoagulant (LA), anticardiolipin antibodies in both IgG and IgM classes (aCL-IgG and aCL-IgM, respectively), antiβ2GPI antibodies in both IgG and IgM classes (antiβ2GPI-IgG and antiβ2GPI-IgM, respectively), ICAM, von Willebrand factor (vWF), TAT, CRP, C3c, C4, and IL-6. ICAM-1 values exceeded the upper reference limit in 9 (15%) patients. vWF levels were increased in 21 (35%) patients. In all patients with elevated ICAM-1 values, vWF were also increased. TAT concentrations were elevated in 12 (20%) people. ICAM-1 were significantly higher in patients with elevated aCL-IgM (> 30 MPL vs ≤ 30 MPL; p < 0.05). Similarly, ICAM-1 were significantly higher in patients with elevated antiβ2-GPI-IgM (> 20 SMU vs ≤ 20 SMU; p < 0.05). There was no significant difference in ICAM-1 levels in relation to LA-positivity. vWF were not significantly different in relation to antiphospholipid antibodies nor the inflammation marker levels. TAT were significantly higher in patients with elevated aCL-IgM (> 30 MPL vs ≤ 30 MPL; p < 0.05). In one third of young patients with stable SLE, signs of endothelial activation/damage were found, as shown by elevated plasma ICAM-1 or vWF. Increased prothrombotic tendency manifested by elevated TAT was found in one fifth of the patients. Elevated anticardiolipin (IgM) and anti-β2-glycoprotein I (IgM) antibodies influence endothelial dysfunction and enhance prothrombotic state.

Validity of Coagulation Activation Markers in Antiphospholipid Syndrome: A Systematic Review and Meta-analysis with a Short Data Report

“…1), 18 studies met the criteria for inclusion in the systematic review and meta-analysis: 6 studies investigated both F1 þ 2 and TAT, 3,12-16 7 studies investigated F1 þ 2 only, [17][18][19][20][21][22][23] and 4 investigated TAT only. [24][25][26][27] One of the studies 27 did not report the number of patients positive and negative for aPL, and at the time of submission of this article the authors had not replied to our request for such numbers. Hence, we could not include their data in the meta-analysis.…”

“…Nevertheless, our overall results show that (1) several authors have used 3,[12][13][14][15][16][24][25][26] and still use TAT as a marker of coagulation activation in APS, 27 oblivious to the early studies on its invalidity 4,31 ; (2) most authors failed to report aPL titers or LA strength, relying solely on aPL positivity to categorize groups, a regrettable phenomenon that we have noticed in other meta-analyses 32,33 ; (3) none of the articles assessed a linear relationship between aPL and F1 þ 2; (4) aPL may interfere in the measurement of F1 þ 2, possibly explaining the wide heterogeneity of the pooled F1 þ 2 data between aPL þve and Àve groups and casting some uncertainty on the effect sizes; (5) relative to controls, aPL Àve SLE patients are in a state of coagulation activation.…”

Glucose-Regulated Protein 78 Autoantibodies Are Associated with Carotid Atherosclerosis in Chronic Obstructive Pulmonary Disease Patients

“…3 ). Several previous reports have described linkages between autoimmunity and atherosclerosis in other disease populations and animal models ( 32 – 34 ). Nonetheless, to our knowledge, this is the first study that has identified an Ag-specific adaptive immune response in COPD patients that is associated with atherosclerosis.…”

Dietary Intake of Free Sugars is Associated with Disease Activity and Dyslipidemia in Systemic Lupus Erythematosus Patients

“…Among autoimmune diseases in general, systemic lupus erythematosus (SLE) is characterised by a loss of tolerance to self-antigens and the production of high titres of serum autoantibodies [1]. Inflammation processes in SLE result in the increase in inflammatory mediators that promote accelerated atherosclerosis, endothelium damage, and SLE progression [2].…”