Circulating soluble E-selectin in early rheumatoid arthritis: a prospective five year study

Abstract

Background: Soluble E-selectin (sE-selectin) is a marker of activation of vascular endothelium. Objective: To examine serum levels of sE-selectin in a cohort of 85 patients with early rheumatoid arthritis (RA) followed up for five years. Methods: sE-selectin levels were assessed annually using an enzyme linked immunosorbent assay (ELISA) and related to simultaneously obtained clinical and laboratory measures. Joint inflammation was evaluated by active joint count, functional status by Health Assessment Questionnaire (HAQ), and radiographic findings in hands and feet by the Larsen method. Laboratory tests included serum C reactive protein (CRP) level, erythrocyte sedimentation rate, blood haemoglobin level, white blood cell count (WBC), and platelet count. Area under the curve (AUC) was calculated for each variable, and Jonckheere's test for ordered alternatives was applied to assess significance of association between sE-selectin AUC tertiles and other variables. Baseline sE-selectin tertiles were related to change in Larsen score and HAQ score at five years. Odds ratios (OR) with 95% confidence interval (CI) were calculated using univariate and multivariate logistic regression. Results: sE-selectin levels were associated with CRP level (p=0.012), WBC (p=0.037), active joint count (p=0.019), progression of joint destruction (p=0.038), and HAQ score at five years (p=0.021), but not with extra-articular symptoms or comorbidity. Baseline sE-selectin levels in the third tertile predicted the HAQ score at five years (OR 4.18, 95% CI 1.15 to 15.22). sE-selectin levels of patients did not differ significantly from those of healthy control subjects. Conclusion: The degree of activation of vascular endothelium is associated with activity and outcome of early RA. R heumatoid arthritis (RA) is an autoimmune disease characterised by a chronic inflammation of unknown cause. In addition to persistent joint inflammation, the hallmark of RA, patients often have systemic inflammation. This is reflected in biochemical tests by, for example, raised C reactive protein (CRP) level, secondary anaemia, and increased platelet count and also in symptoms such as loss of weight, fatigue, malaise, and low grade fever. During the course of the disease patients may develop extra-articular features such as alveolitis, glomerulonephritis, and vasculitis. 1 Chronic systemic inflammation may also be a risk factor for cardiovascular morbidity 2 3 and mortality. 4 Systemic inflammation is characterised by activation of the vascular endothelium. Endothelial cells stimulated in vitro with proinflammatory cytokines express E-selectin, a cell adhesion molecule which promotes initial tethering of leucocytes to endothelium, a prerequisite for leucocyte emigration into tissues (reviewed by Ebnet and Vestweber 5 ). Endothelial cells release, most probably by a proteolytic cleavage, E-selectin from their surfaces.6 Soluble E-selectin (sEselectin) is considered to be a specific marker of endothelial cell activation during systemic inflammation. Low levels o...

Coexpression of chemokine receptors CCR5, CXCR3, and CCR4 and ligands for P‐ and E‐selectin on T lymphocytes of patients with juvenile idiopathic arthritis

“…P‐ and E‐selectin expressed on activated endothelial cells mediate rolling and emigration of leukocytes, including T cells, from blood at sites of inflammation (15, 20). Soluble forms of P‐ and E‐selectin shed by endothelium are increased in the blood and SF in RA and JIA, and levels of soluble E‐selectin are correlated with other markers of disease activity (22–24). Ligands for P‐ and E‐selectin on activated T cells are generated by the induction of fucosyl transferase IV and VII (20, 27, 34, 44).…”

“…The selectins are involved in the capture of leukocytes from the blood and their subsequent migration into tissue (15, 20). In both RA and JIA, P‐ and E‐selectin are up‐regulated on synovial blood vessels and their soluble forms are elevated in blood (21–24). These adhesion molecules likely are important in the recruitment of T cells to the joints in RA and JIA, as demonstrated in experimental arthritis (25, 26).…”

Plasma indices of endothelial and platelet activation in Rheumatoid Disease: Relationship to cardiovascular co-morbidity

“…In this study, sE-sel levels were similar among RD patients, their subgroups, and controls. Some previous studies have reported higher sE-sel levels in RD [23], as well as a reduction following anti-inflammatory treatment [24], whilst others have not shown significant differences [21,25]. In a longitudinal study, sE-sel did correlate with CRP, and was predictive of adverse radiological findings after 5 years [25].…”

Soluble vascular cell adhesion molecular-1 is a potential biological indicator of hemophilic arthropathy

“…[29] The latter group of studies that failed to find associations between patients with RA and controls all employed a cross-sectional study design and had examined patients with chronic RA. [30] In this study, the sE-selectin level was not significantly elevated in patients with hemophilia A. This might be because in our analyses, we did not stratify patients on the basis of the severity of hemophilic arthropathy (i.e., acute and chronic inflammation).…”