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Source publication
Objectives:
To investigate the association between endothelial progenitor cells (EPCs) and Takayasu arteritis (TA). Subjects andMethods: A total of 39 subjects were included in this study: 12 subjects had been diagnosed with active TA, 11 had active Behçet disease (BD), and 16 were healthy controls. The EPCs, erythrocyte sedimentation rate (ESR),...
Context in source publication
Context 1
... mean ages of the TA, BD, and healthy groups were 32.7 ± 6.5, 31.9 ± 8.5, and 33.6 ± 9.0 years, respectively ( p = 0.866). The clinical manifestations of the groups are shown in Table 1 Table 2 . Demo- graphic characteristics and biochemical measurements of the groups are shown in Table 3 . ...
Citations
... Circulating endothelial progenitor cells (EPCs) were elevated in TAK when compared with Behcet's disease or with healthy controls. The levels of circulating EPCs moderately correlated with ESR and CRP [128]. A study of 35 patients with TAK (20 with active disease) reported similar levels of soluble E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) in active or inactive TAK. ...
Takayasu arteritis (TAK) is a less common large vessel vasculitis where histopathology of involved arteries is difficult to access except during open surgical procedures. Assessment of disease activity in TAK, therefore, relies on surrogate measures. Clinical disease activity measures such as the National Institutes of Health (NIH) score, the Disease Extent Index in TAK (DEI.TAK) and the Indian TAK Clinical Activity Score (ITAS2010) inconsistently associate with acute phase reactants (APRs). Computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), or color Doppler Ultrasound (CDUS) enables anatomical characterization of stenosis, dilatation, and vessel wall characteristics. Vascular wall uptake of 18-fluorodeoxyglucose or other ligands using positron emission tomography computerized tomography (PET-CT) helps assess metabolic activity, which reflects disease activity well in a subset of TAK with normal APRs. Angiographic scoring systems to quantitate the extent of vascular involvement in TAK have been developed recently. Erythrocyte sedimentation rate and C-reactive protein have a moderate performance in distinguishing active TAK. Numerous novel biomarkers are under evaluation in TAK. Limited literature suggests a better assessment of active disease by combining APRs, PET-CT, and circulating biomarkers. Validated damage indices and patient-reported outcome measures specific to TAK are lacking. Few biomarkers have been evaluated to reflect vascular damage in TAK and constitute important research agenda.
... Circulating endothelial precursor cells are markers of endothelial cell damage and repair/angiogenesis. A small number of studies address the number of endothelial precursor cells in the peripheral blood in TA, using different gating strategies to identify these cells (CD309-VEGFR2/CD133/CD34 [106,109] or CD146/CD31/CD34+, CD45− cells [110]). Their number in peripheral blood has been reported to correlate with disease activity in TA [109,110], although a more recent study did not confirm these results [106] and the exact mechanism underlying this occurrence is scarcely understood. ...
... A small number of studies address the number of endothelial precursor cells in the peripheral blood in TA, using different gating strategies to identify these cells (CD309-VEGFR2/CD133/CD34 [106,109] or CD146/CD31/CD34+, CD45− cells [110]). Their number in peripheral blood has been reported to correlate with disease activity in TA [109,110], although a more recent study did not confirm these results [106] and the exact mechanism underlying this occurrence is scarcely understood. ...
Purpose of Review
Large vessel vasculitides (LVVs) are inflammatory conditions of the wall of large-sized arteries, mainly represented by giant cell arteritis (GCA) and Takayasu arteritis (TA). The inflammatory process within the vessel wall can lead to serious consequences such as development of aneurysms, strokes and blindness; therefore, early diagnosis and follow-up of LVV are fundamental. However, the arterial wall is poorly accessible and blood biomarkers are intended to help physicians not only in disease diagnosis but also in monitoring and defining the prognosis of these conditions, thus assisting therapeutic decisions and favouring personalised management. The field is the object of intense research as the identification of reliable biomarkers is likely to shed light on the mechanisms of disease progression and arterial remodelling. In this review, we will discuss the role of blood biomarkers in LVVs in the light of the latest evidence.
Recent Findings
In clinical practice, the most widely performed laboratory investigations are the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). However, these indices may be within normal limits during disease relapse and they are not reliable in patients receiving interleukin-6 (IL-6) receptor inhibitors. New biomarkers struggle to gain traction in clinical practice and no molecule with good accuracy has been identified to date. IL-6, a pro-inflammatory cytokine that drives CRP synthesis and increases the ESR, is one of the most promising biomarkers in the field. IL-6 analysis is increasingly performed, and serum levels are more sensitive than ESR for active GCA and might reflect persistent inflammation with high risk of relapse in patients on IL-6 receptor inhibitors. A future with biomarkers that reflect different disease features is an important aspiration. Accordingly, intense effort is being made to identify IL-6-independent inflammatory biomarkers, such as S100 proteins, pentraxin-3 and osteopontin. Moreover, metalloproteinases such as MMP2/9 and angiogenic modulators such as VEGF, YLK-40 and angiopoietins are being studied as markers of arterial remodelling. Lastly, biomarkers indicating organ damage may guide prognostic stratification as well as emergency therapeutic decisions: the most promising biomarkers so far identified are NT-proBNP, which reflects myocardial strain; pentraxin-3, which has been associated with recent optic nerve ischemia; and endothelin-1, which is associated with ischaemic complications.
Summary
Currently, the use of these molecules in clinical practice is limited because of their restricted availability, lack of sufficient studies supporting their validity and associated costs. Further evidence is required to better interpret their biological and clinical value.
... Test accuracy results: inflammatory markers. The utility of measuring erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients with TAK was evaluated in three single-arm studies and showed a sensitivity and specificity of 75% and a low overall test accuracy (17)(18)(19). Although ESR and CRP are neither highly sensitive or specific for disease activity in TAK, they are still used in clinical practice to monitor disease activity and are incorporated into the NIH disease activity score as well as the Indian Takayasu Clinical Activity Score (ITAS) disease activity measurement (1,20). ...
... Although there has been research evaluating potential biomarkers in TAK, in practice we tend to incorporate measurements of ESR and CRP as part of our assessment for active disease. Three single-arm studies showed a sensitivity and specificity of 75% for elevations in ESR and CRP correlating with clinical disease activity and a low overall test accuracy (17)(18)(19). Because of the unreliability of lab parameters combined with the nonspecific disease manifestations of patients with active TAK, heavy reliance is placed on imaging modalities in both diagnosing and monitoring patients with TAK. ...
Objective
Takayasu’s arteritis (TAK) is a granulomatous large‐vessel vasculitis primarily affecting the aorta and its proximal branches. TAK can be a difficult disease to diagnose and manage given the rarity of the disease as well as current limitations in biomarkers, imperfect imaging modalities, and few randomized controlled trials.
Methods
In developing the American College of Rheumatology/Vasculitis Foundation guideline for the management of TAK, we performed an extensive systematic literature review to guide our recommendations. We included RCTs first. When RCTs were not available, we included observational studies that reported on patient‐important outcomes for the intervention and comparison. When studies with comparative data were not available, we included case series that present patient‐important outcomes for either the intervention or the comparison.
Results
Three hundred forty‐seven articles were included for full review to answer 27 population, intervention, comparison, and outcome questions related to TAK. Ten studies were evaluated that addressed the use of glucocorticoids (GCs), non‐GC nonbiologic therapies, as well as biologics in treating TAK. A total of 33 studies, including 8 comparative studies, were included to determine the test accuracy of commonly available diagnostic tests for TAK.
Conclusion
This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the management of TAK.
... 14 On the other hand, Nakatani et al found higher levels of EPCs following an increase in CECs in Kawasaki disease, particularly in patients with complicated coronary artery lesions, suggesting that EPCs may be involved in the repair of endothelial damage. 13 Poor and contrasting data on abnormalities in CECs and EPCs, derived from inadequate methodologies, are currently available in BS. 15,16 This study aimed to evaluate whether the concentrations of CECs and EPCs, as assessed by a standardized flow cytometry protocol, are increased in patients affected by BS and significantly correlate with clinical features. It would provide explorative data on the vascular involvement in the disease pathogenesis and the potential role of these cells as biomarkers of disease activity or damage accrual. ...
... Conversely, in other studies, where BS was included among other vasculitides, no increase in CECs concentration was demonstrated. 16 Compared with previous studies, our findings on CECs in BS are the first derived by a validated flow cytometry protocol. Indeed, most data on CECs are so far obtained by immunomagnetic separation protocols, where endothelial cells are isolated from whole blood with magnetic particles coated with anti-endothelial antibodies (eg, anti-CD146) and counted by fluorescence microscopy. ...
Purpose
To explore the potential role of circulating endothelial cells (CECs) and their progenitors (EPCs) as biomarkers of disease activity and damage accrual in patients with Behçet’s syndrome (BS), by using a standardised and reliable flow cytometry protocol.
Patients and methods
CECs and EPCs were assessed in 32 BS patients and 11 gender/age/smoking habits matched healthy controls (HC). They were identified by flow cytometry as alive/nucleated/CD45-negative/CD34-bright/CD146-positive and alive/nucleated/CD45-negative/CD34-bright/CD309-positive events, respectively. In BS patients, demographic and clinical features, including disease activity (assessed by Behçet’s disease current disease activity form, BDCAF) and irreversible damage accrual (by the vasculitis damage index, VDI) were recorded. Uni- and multivariate analysis were performed to compare the CECs and EPCs concentrations in BS vs HC and to identify potential associations with demographic or clinical features.
Results
The CECs concentration was significantly higher in the BS patients than HCs [median (IQR) 15.0 (7.5–23.0) vs 6.0 (2.0–13.0) CECs/mL, p=0.024]. In BS patients, no significant associations were found between CECs and demographic features, present and past clinical manifestations, BDCAF score and ongoing treatment. A significant association was observed between CECs and organ damage, as assessed by the VDI (rho 0.356, p=0.045). Higher levels of CECs were especially associated with vascular damage [median (IQR) 23.0 (14.0–47.0) vs 13.0 (6.0–19.0) CECs/mL, p=0.011], including arterial aneurysm and stenosis, complicated venous thrombosis, cerebrovascular accident. The concentration of EPCs did not significantly differ between the BS and HC [median 26.5 (13.0–46.0) vs 19.0 (4.0–42.0) EPCs/mL, p=0.316] and no significant associations were observed between their levels and any clinical characteristic.
Conclusion
Our study suggests that the CECs concentration is significantly higher in BS than healthy subjects, and it mainly correlates with vascular damage. A longitudinal extension of the present study on a wider cohort would be useful to validate the potential role of CECs as a marker or, hopefully, predictor of vascular damage in BS.
... 13 However in vascular BD patients they observed an increased EPC count, although not statistically significant. They were also unable to show any correlation between EPC High levels of endothelial progenitor cells and circulating endothelial cells in patients... 18 However, the difference in EPC levels between BD patients and controls was not statistically significant. The EPC evaluation criteria in that study differed from ours, and the sample was also very small, which could explain the different results. ...
Background:
Behçet's disease is a multisystemic vasculitis, associated with vascular endothelial dysfunction. Currently, the prognosis is unpredictable, because there is still no valid laboratory marker indicating the disease activity in Behçet's disease. Endothelial progenitor cells and circulating endothelial cells are newly introduced hematological markers which are presumed to take part in the pathogenesis of vasculitis.
Objectives:
To evaluate the levels of endothelial progenitor cells and subtypes and circulating endothelial cells in patients with Behçet's disease and to describe their relationship with the disease activity.
Methods:
A total of 45 patients with Behçet's disease and 28 healthy controls were included in the study. Endothelial progenitor cells (CD34+CD133+KDR+ as early endothelial progenitor cells and CD34+KDR+ as late endothelial progenitor cells), and circulating endothelial cells (CD34+CD133+) were measured by flow cytometry.
Results:
The mean plasma level of endothelial progenitor cells and circulating endothelial cells, vascular endothelial growth factor, matrix metalloproteinase-9, C-reactive protein, and erythrocyte sedimentation rate were significantly higher in patients with Behçet's disease. All of these parameters except circulating endothelial cells were also found to be higher in patients with active disease than in patients with inactive disease. Early endothelial progenitor cells showed significant correlations with C-reactive protein and circulating endothelial cells.
Study limitations:
The cross-sectional nature of the study and patient characteristics such as being under treatment, which can affect endothelial progenitor cells numbers.
Conclusion:
The increase in endothelial progenitor cells may play an essential role in the repair of endothelial injury in Behçet's disease, especially in the active period of the disease. Thus, endothelial progenitor cells can indicate the disease activity. In addition, endothelial progenitor cells and circulating endothelial cells can be used as endothelial repair and injury markers for Behçet's disease, respectively.
... Following this line of research, other authors demonstrated an expansion of Th17 and elevated serum IL17 and IL23, with no correlation with disease activity (160), but potentially associated with age at disease onset and relapse rate (161). It has been suggested that increased levels of chromogranina A correlate with vascular remodelling (162), while increased endothelial progenitor cells, released in response to vascular injury and tissue ischaemia, were found to correlate with inflammatory markers and acrotism in patients with TAK (163). Plasma pentraxin-3 (PTX-3) is released by dendritic cells, macrophages and vascular cells in response to proinflammatory signals; increased levels of PTX-3 have been previously described both in GCA and TAK supporting a connection with disease activity (164,165). ...
Systemic vasculitis is a group of heterogeneous, disabling disorders. Great interest has recently arisen in pathophysiology, clinical phenotypes and therapy of large- and small-vessel vasculitis. The general work hypothesis has been to promote research focused on disease-related pathogenetic pathways, with the ultimate goal of identifying novel diagnostic and prognostic biomarkers, thus leading towards more effective targeted treatments. Following the previous annual reviews of this series, we will hereby provide a critical digest of the recent literature on small- and large-vessel systemic vasculitis, with a specific focus on novel possible disease-related biomarkers and their impact on current and future therapies.
Vascular stem/progenitor cells (VSCs) are an important source of all types of vascular cells needed to build, maintain, repair, and remodel blood vessels. VSCs, therefore, play critical roles in the development, normal physiology, and pathophysiology of numerous diseases. There are four major types of VSCs, including endothelial progenitor cells (EPCs), smooth muscle progenitor cells (SMPCs), pericytes, and mesenchymal stem cells (MSCs). VSCs can be found in bone marrow, circulating blood, vessel walls, and other extravascular tissues. During the past two decades, considerable progress has been achieved in the understanding of the derivation, surface markers, and differentiation of VSCs. Yet, the mechanisms regulating their functions and maintenance under normal and pathological conditions, such as in eye diseases, remain to be further elucidated. Owing to the essential roles of blood vessels in human tissues and organs, understanding the functional properties and the underlying molecular basis of VSCs is of critical importance for both basic and translational research.
