Disease Activity In Takayasu Arteritis Research Articles

NMR-Based Serum Metabolomics of Patients with Takayasu Arteritis: Relationship with Disease Activity.

Takayasu arteritis (TA) is a large vessel vasculitis of unknown pathogenesis. Assessment of disease activity is a challenge, and there is an unmet need for relevant biomarker(s). In our previous study, NMR based serum metabolomics had revealed distinctive metabolic signatures in TA patients compared with age/sex matched healthy controls and systemic lupus erythematosus (SLE). In this study we investigate whether the metabolites correlate with disease activity. Patients with TA fulfilling American College of Rheumatology (ACR) criteria were enrolled, and disease activity was assessed using Indian Takayasu Clinical Activity Score using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. Sera were analyzed using 800 MHz NMR spectrometer to identify metabolites [based on partial least squares discriminant analysis (PLS-DA) VIP (variable importance in projection) score > 1.0 and permutation test, p-value <0.01]. 45 active and 53 inactive TA patients with median age 27 [(IQR) 22-35 years] and 27 [(IQR) 23-37 years], female to male ratio 3.5:1 and 4.9:1, and median duration of illness 5 [(IQR) 2-9 years] and 3 [(IQR) 1-6 years], respectively, were enrolled. The key metabolites with highest discriminatory potential in active TA (ITAS-A ≥ 4) were glutamate and N-acetyl glycoprotein (NAG), both elevated, with area under the curve 0.775 and 0.769 ( p-value <0.001). On follow up assessment, metabolic spectra started to differ with change in disease activity. This large cohort of patients revealed metabolic profiles discriminating between clinically active and inactive TA patients. It suggests glutamate and NAG have strong potential as biomarkers for disease activity in TA and may serve as a guide to therapy. We are now working to further validate these results in longitudinal studies.

Increased Arterial Stiffness Adversely Affects Left Ventricular Mechanics in Patients With Pediatric Takayasu Arteritis From a Toronto Cohort.

Takayasu arteritis (TA) is characterized by extensive aortic, large and midsize arterial wall inflammation. The aim of this study was to assess the morphological and elastic properties of the aorta and large arteries and the impact on left ventricular (LV) mechanics in children with TA. Seven pediatric TA patients (6 female patients, 13.8 ± 3.2 years) were assessed with magnetic resonance imaging, vascular ultrasound, applanation tonometry, and echocardiography from February 2015 until July 2017 and compared with 7 age- and sex-matched controls. Takayasu arteritis disease activity was assessed clinically by the Pediatric Vasculitis Activity Score (PVAS). Pediatric TA patients showed increased carotid-to-radial artery pulse wave velocity (8.1 ± 1.8 vs. 6.4 ± 0.6 m/s, p = 0.03) and increased carotid-to-femoral artery pulse wave velocity (8.3 ± 1.9 vs. 5.1 ± 0.8 m/s, p < 0.01) when compared with controls. Patients demonstrated increased LV mass index (74.3 ± 18.8 vs. 56.3 ± 10.9 g/m, p = 0.04), altered myocardial deformation with increased basal rotation (-9.8 ± 4.5 vs. -4.0 ± 2.0 degrees, p = 0.01) and torsion (19.9 ± 8.1 vs. 9.1 ± 3.1 degrees, p = 0.01), and impaired LV diastolic function with decreased mitral valve E/A ratio (1.45 ± 0.17 vs. 2.40 ± 0.84, p = 0.01), increased mitral valve E/E' ratio (6.8 ± 1.4 vs. 4.9 ± 0.7, p < 0.01), and increased pulmonary vein A-wave velocity (26.7 ± 5.7 vs. 16.8 ± 3.3 cm/s, p = 0.03). Carotid-to-radial artery pulse wave velocity was associated with systolic (R = 0.94, p < 0.01), diastolic (R = 0.85, p = 0.02), and mean blood pressure (R = 0.91, p < 0.01), as well as disease activity by PVAS (R = 0.75, p = 0.05). The PVAS was associated with carotid-to-radial artery pulse wave velocity (R = 0.75, p = 0.05), as well as systolic (R = 0.84, p = 0.02), diastolic (R = 0.82, p = 0.03), and mean blood pressure (R = 0.84, p = 0.02). Increased arterial stiffness is present in pediatric TA patients and associated with increased blood pressure and TA disease activity. Pediatric TA patients demonstrate altered LV mechanics, LV hypertrophy, and impaired diastolic function.

Radiology and biomarkers in assessing disease activity in Takayasu arteritis.

Takayasu arteritis (TA) is a rare and chronic large-vessel vasculitis that predominantly affects aorta and its main branches. It occurs mainly in females <40years. Precise assessment of disease activity is one of the major difficulties in the long-term management of TA. Until now, the accuracy of traditional activity index is still controversial. During these years, due to rapid development of radiological technology and researches of pathogenesis, new measurements and biomarkers have been applied to monitor disease activity for TA. Thus, in this review, we mainly discuss the benefits and limitations of recent developments of radiology and biomarkers for disease activity assessment in TA.

Serum amyloid A as a marker of disease activity and treatment response in Takayasu arteritis.

Assessment of disease activity in Takayasu arteritis (TA) is challenging. We aimed to study utility of serum amyloid A (SAA) to assess disease activity and its association with SAA gene polymorphisms, if any, in our TA patients. Serum of 99 consecutive adult TA patients and 40 healthy controls were assayed for SAA. Depending on the ITAS2010 and ITAS-CRP score, patients were designated as having active disease if ITAS2010≥2 or ITAS-CRP≥3 and stable disease if ITAS2010=0 or ITAS-CRP is ≤1. Clinical ITAS of 0 with raised inflammatory markers scoring a ITAS-CRP of 2 was considered as indeterminate for disease activity assessment. Repeat SAA levels for active group was measured after 6months from baseline. SAA levels between active and stable disease as well as serial levels were compared. DNA of 40 patients and controls were genotyped for SAA polymorphisms (rs12218, rs2468844) and the allele frequencies were compared. At baseline, SAA levels were higher in patients as compared to controls (137.4 vs 100.8ng/ml, p=0.001) and higher in patients with active disease (166.4ng/ml) than those with stable disease (98.2ng/ml), p=0.001. SAA decreased during follow-up in treatment responders (189.9ng/ml at baseline vs 119.0ng/ml at follow-up, p=0.008); in contrast, there was no significant change among non-responders during follow-up. Allelic frequencies of SAA gene polymorphisms did not differ between cases and controls. SAA may be a reliable biomarker to assess disease activity and treatment response in TA.

Are cytokines and chemokines suitable biomarkers for Takayasu arteritis?

There is a growing need for disease related biomarkers in Takayasu arteritis (TA).The assessment of pro-inflammatory cytokines and chemokines in TA may provide a better understanding of its pathophysiology, and circulating levels of these mediators may act as biomarkers of disease activity. Serum level of interleukin 6 (IL-6) is a potential biomarker for TA, which is mostly associated with TA status and disease activity. Associations between TA and serum/plasma levels of other cytokines are less clear. mRNA expression of IL-4 and tumor necrosis factor α (TNFα) are constitutively increased in peripheral blood mononuclear cells (PBMC) from TA patients and the expression of both cytokines increases even more after PBMC stimulation in vitro, while the expression of IL-10 mRNA decreases. In addition, circulating T cells from TA patients produce increased levels of both Th1- and Th17-related cytokines upon in vitro stimulation. In the aorta from TA patients, an increased expression of interferon γ (IFNγ), IL-6, IL-12 and IL-17 has been described. Regarding circulating chemokines in TA, serum/plasma levels of IL-8 (CXCL8), CCL2 and CCL5 were shown to be elevated in TA patients compared with healthy controls as well as in TA patients with active disease compared with those in remission. Serum IL-6 seems to be the best biomarker for disease state and disease activity in TA and increased Th1 and Th17 responses are predominant in the pathophysiology of TA.

Vessel Wall Inflammation of Takayasu Arteritis Detected by Contrast-Enhanced Magnetic Resonance Imaging: Association with Disease Distribution and Activity.

AimsThe assessment of the distribution and activity of vessel wall inflammation is clinically important in patients with Takayasu arteritis. Magnetic resonance imaging (MRI) is a useful tool, but the clinical utility of late gadolinium enhancement (LGE) in Takayasu arteritis has yet to be determined. The aim of the present study was to evaluate the utility of LGE in assessing vessel wall inflammation and disease activity in Takayasu arteritis.Methods and ResultsWe enrolled 49 patients with Takayasu arteritis who had undergone 1.5 T MRI. Patients were divided into Active (n = 19) and Inactive disease (n = 30) groups. The distribution of vessel wall inflammation using angiography and LGE was assessed by qualitative analysis. In 79% and 63% of patients in Active and Inactive groups, respectively, greater distribution of vessel wall inflammation was observed with LGE than with conventional angiography. MRI values of pre- and post-contrast signal-to-noise ratios (SNR), SNR increment (post-SNR minus pre-SNR), pre- and post-contrast contrast-to-noise ratios (CNR), and CNR increment (post-CNR minus pre-CNR) were evaluated at arterial wall sites with the highest signal intensity using quantitative analysis of post-contrast LGE images. No statistically significant differences in MRI parameters were observed between Active and Inactive groups. Contrast-enhanced MRI was unable to accurately detect active disease.ConclusionContrast-enhanced MRI has utility in detecting the distribution of vessel wall inflammation but has less utility in assessing disease activity in Takayasu arteritis.

Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis.

We aimed to clarify the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the management of large-vessel vasculitis (LVV), focusing on 3 issues which are as follows: describe and determine the different FDG-PET criteria for the diagnosis of vascular inflammation, the performance of FDG-PET for the diagnosis of large-vessel inflammation in giant cell arteritis (GCA) patients, and the performance of FDG-PET to evaluate the disease inflammatory activity in Takayasu arteritis (TA) patients.MEDLINE, Cochrane Library, and EMBASE database were searched for articles that evaluated the value of FDG-PET in LVV, from January 2000 to December 2013. Inclusion criteria were American College of Rheumatology criteria for GCA or TA, definition PET positivity threshold, and >4 cases included. Sensitivity (Se) and specificity (Sp) of FDG-PET for the diagnosis of large-vessel inflammation were calculated from each included individual study, and then pooled for meta-analysis with a random-effects model.Twenty-one studies (413 patients, 299 controls) were included in the systematic review. FDG-PET showed FDG vascular uptake in 70% (288/413) of patients and 7% (22/299) of controls. Only vascular uptake equal to or higher than the liver uptake was significantly different between GCA/TA patients and controls (P < 0.001). The meta-analysis of GCA patients (4 studies, 57 patients) shows that FDG-PET has high Se and Sp for the diagnosis of large-vessel inflammation in GCA patients in comparison to controls, with a pooled Se at 90% (95% confidence interval [CI], 79%–93%) and a pooled Sp at 98% (95% CI, 94%–99%). The meta-analysis of TA patients (7 studies, 191 patients) shows that FDG-PET has a pooled Se at 87% (95% CI, 78%–93%) and Sp at 73% (95% CI, 63%–81%) for the assessment of disease activity in TA, with up to 84% Sp, with studies using National Institutes of Health criteria as the disease activity assessment scale.FDG-PET showed good performances in the diagnosis of large-vessel inflammation, with higher accuracy in GCA patients than in TA patients. Although a vascular uptake equal to or higher than the liver uptake appears to be a good criterion for the diagnosis of vascular inflammation, further studies are needed to define the threshold of significance as well as the clinical significance of the vascular uptake.

Association of abnormal lipid spectrum with the disease activity of Takayasu arteritis.

Our study aimed to determine whether proatherogenic lipid profiles exist in patients with active Takayasu arteritis (TA) and assess the relationship between different lipid profiles and disease activity in TA. A total of 132 premenopausal female patients with TA and 100 sex-, age-, and body mass index-matched healthy controls were included in our study. The clinical data were collected in detail from all participants. Patients with active TA had significantly lower levels of apolipoprotein A1 (apoA1) (1.47 ± 0.30 vs. 1.99 ± 0.33 mmol/L, p < 0.001) and lower levels of high-density lipoprotein cholesterol (HDL-C) (1.23 ± 0.33 vs. 1.68 ± 0.38 mmol/L, p < 0.001) than patients with inactive TA. However, they had higher ratios of apolipoprotein B (apoB)/apoA1 (0.74 ± 0.27 vs. 0.48 ± 0.14, p < 0.001) compared with patients with inactive TA. Multiple linear regression analysis demonstrated that the apoB/apoA1 ratio was independently associated with TA activity (β = 0.38, p = 0.04). In addition, multivariate stepwise forward regression analysis showed that the apoB/apoA1 ratio was the major determinant for high-sensitivity C-reactive protein (β = 0.58, p = 0.002). Our findings indicate that patients with active TA had proatherogenic lipid profiles. In addition, the ratio of apoB to apoA1 could be used as a marker for monitoring and targeting patients with TA.

GW25-e3539 Association of dyslipoproteinemia with the disease activity of Takayasu arteritis

GW25-e3539 Association of dyslipoproteinemia with the disease activity of Takayasu arteritis

The association of red blood cell distribution width with anemia and inflammation in patients with Takayasu arteritis

BackgroundRed blood cell distribution width (RDW) has been shown to be related to both anemia and inflammation in various diseases. However, the role of RDW in patients with Takayasu arteritis (TA) is unknown. Therefore, we investigated the association of RDW with anemia, inflammation, and disease activity in TA. MethodsRDW was determined in 156 patients with TA and in 156 control subjects. Anemia status and disease activity were defined according to the World Health Organization and National Institutes of Health criteria, respectively. ResultsRDW was significantly increased in patients with anemia (14.6±2.2) compared with those without anemia (13.6±1.3, p<0.001) and control subjects (12.7±0.6, p<0.001). Regardless of the presence of anemia, RDW showed correlation with high-sensitivity C-reactive protein (hs-CRP) (both p<0.05). RDW was higher in active TA than inactive TA in patients without anemia (14.1±1.5 vs. 13.3±1.1, p=0.001). Moreover, multiple regression analysis showed that hs-CRP and mean corpuscular volume were independently associated with RDW. ConclusionsRDW is influenced by both anemia and inflammation, and RDW may be a useful marker to assess disease activity in patients without anemia.

AB0572 Additional Role of FDG Pet/Ct in the Assessment of Disease Activity in Takayasu Arteritis

BackgroundTakayasu arteritis (TA) is an inflammatory vasculitis, typically affecting young women with important morbidity and mortality and a largely unknown pathogenesis. Disease activity (DA) evaluation is still a major unresolved...

Diagnosis and Assessment of Disease Activity in Takayasu Arteritis: A Childhood Case Illustrating the Challenge

Takayasu Arteritis (TA) is a rare, debilitating large vessel vasculitis occurring in patients of all ages, including infants, but the disease most commonly presents in the third decade. Diagnosis is often delayed and consequently TA is associated with significant morbidity and mortality. Accurate methods of monitoring disease activity or damage are lacking and currently rely on a combination of clinical features, blood inflammatory markers, and imaging modalities. In this report we describe a case of a 14-year-old boy with childhood-onset TA who, despite extensive negative investigations, did indeed have on-going active large vessel vasculitis with fatal outcome. Postmortem analysis demonstrated more extensive and active disease than originally identified. This report illustrates and discusses the limitations of current modalities for the detection and monitoring of disease activity and damage in large vessel vasculitis. Clinicians must be aware of these limitations and challenges if we are to strive for better outcomes in TA.

Clinical Utility of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Takayasu Arteritis — A Report of 3 Demonstrative Cases

Takayasu arteritis (TA) is a granulomatous disease affecting aorta and its main branches1. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) may be useful in assessing disease activity of TA. We describe 3 demonstrative cases. In case 1, a 44-year-old man was admitted with a fever of unknown origin. The levels of acute phase reactants (APR) were elevated. Pulse in the left upper arm was undetectable and the …

FRI0476 Relative fdg accumulation of the aortic wall lesions to aortic blood pool in 18f-fdg-pet and pet/ct is a useful parameter for assessing the disease activity of takayasu arteritis

BackgroundThere is accumulating evidence that 18F-fluolodeoxyglucose-positron emission tomography (FDG-PET) and PET/ computed tomography (PET/CT) is useful for monitoring patients with Takayasu arteritis (TA).ObjectivesTo investigate a quantitative indicator in FDG-PET or...

Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010)

There are no valid instruments to measure disease activity in Takayasu arteritis (TA). We aim to provide a valid measure to assess clinical disease activity with or without incorporating acute phase reactants. The Indian Takayasu Clinical Activity Score (ITAS) was initially derived from disease manifestations scored in the Disease Extent Index (DEI.Tak). The ITAS was validated by a group of physicians scoring both live and paper cases for inter-rater reliability (IRR), convergence with BVAS, correlation with the Physician's Global Assessment (PGA) and ESR/CRP. It was further validated at a single centre in 177 patients for its ability to discriminate between active and inactive disease state at first visit and sensitivity to change in 132 active patients measured serially at two follow-up visits. ITAS-A also included graded scores for ESR/CRP. The final ITAS2010 contains 44 items with 33 features arising from the cardiovascular system. Seven key items are weighted to score 2 and all others score 1 only. Inter-observer variability was highly satisfactory (IRR 0.97). The ITAS showed superior inter-rater agreement compared with the BVAS (IRR 0.9) and PGA (IRR 0.82). In the single-centre study, median ITAS scores at first visit were significantly higher in active disease (5.62 ± 3.14) compared with grumbling (3.36 ± 1.96) and inactive disease (1.27 ± 1.26, P < 0.0001). The therapy induced a significant decrease in the ITAS2010 but the higher ITAS-A scores remained elevated. The ITAS2010, validated in over 300 TA patients and sensitive to change, is a useful measure of clinical disease activity for patient monitoring. Higher ITAS-A scores suggest poor control of active disease by current therapy.

The Comparison in Assessing Disease Activity among MMP-3, CRP and PTX3 According to Max SUV from FDG-PET in Takayasu Arteritis

Conventionally, MMP-3 was examined in diagnosing Takayasu arteritis (TA), however, we sometimes experienced MMP-3 tended to be increasing after the corticosteroid treatment. Recently, arterial max SUV from FDG-PET have showed usefulness in assessing disease activity in TA. We assessed diagnostic ability with biomarkers which represent inflammation. Consecutive 20 patients with TA underwent FDG-PET/CT were enrolled. The patients were divided to active and inactive according to NIH criteria. CRP, PTX3 and MMP-3 were examined in the nearest day of obtained imaging data.

Role of FDG PET-CT in Takayasu Arteritis: Sensitive Detection of Recurrences

The aim of this study was to investigate whether the maximum standardized uptake value (max SUV) of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) provides a quantitative indication of disease activity in Takayasu arteritis (TA) cases. The clinical value of FDG-PET for assessing TA has been investigated. Clinical evaluation of disease activity is often difficult, because most patients develop recurrent inflammation while receiving corticosteroid treatment. Thirty-nine TA patients underwent FDG-PET/CT at Tokyo Medical and Dental University from 2006 to 2010 (35 women and 4 men; median age, 30 years). Disease activity was defined according to National Institutes of Health criteria. Biomarkers including C-reactive protein and erythrocyte sedimentation rate were measured. Forty subjects without vasculitis served as control subjects. The max SUV was significantly higher in active than in inactive cases and control subjects (active [n = 27], median value, 2.7 vs. inactive [n = 12], 1.9; control [n = 40], 1.8; p < 0.001 each). Given a max SUV cutoff of 2.1, sensitivity for active-phase TA was 92.6%, specificity 91.7%, positive predictive value 96.2%, and negative predictive value 84.6%. In receiver-operating characteristic curves comparison, max SUV was superior to C-reactive protein (p < 0.05) and erythrocyte sedimentation rate (p < 0.05). Max SUV was significantly higher in relapsing on treatment cases (n = 17) than in stable on treatment cases (n = 12) (median value, 2.6 vs. 1.9; p < 0.001). FDG-PET/CT is useful for detection of active inflammation not only in patients with active TA before treatment but also in relapsing patients receiving immunosuppressive agents. The max SUV is useful for assessing subtle activity of TA with high sensitivity.

The role of 18F‐fluorodeoxyglucose–positron emission tomography in the assessment of disease activity in patients with Takayasu arteritis

The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.

MMP-9 and IL-6 are potential biomarkers for disease activity in Takayasu's arteritis

Takayasu arteritis (TA) is an idiopathic vasculitis which primarily affects large elastic arteries and the disease onset and progress are often insidious, and the systemic manifestations are always absent or go unrecognized [1,2]. Furthermore, TA disease tends to progress despite treatment with glucocorticoid and/or immunosuppressive agents. So, it is crucial to find appropriate biomarkers to monitor TA disease activity and possibly predict exacerbations, in order to aid early treatment; however, traditional biomarkers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) lack the sensitivity and specificity to accurately monitor disease status [3,4].

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

IntroductionThe current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA.MethodsThis study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay.ResultsUnacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity.ConclusionsThis study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity.