Disease Activity In Takayasu Arteritis Research Articles

Cerebrovascular implications of takayasu arteritis: a review.

Takayasu arteritis (TA) is a rare, chronic, inflammatory large-vessel vasculitis that affects the aorta and its main branches, including the cerebrovascular system. This review analyzes current knowledge and patient outcomes concerning the cerebrovascular implications of TA. A literature search, with publications from 1994 to 2024, identified pertinent studies through PubMed. An illustrative case report details a 19-year-old female with Type 1 TA, illustrating the complex decision required in the absence of surgical or endovascular options. Our results offer a demographic analysis of 1,698 TA patients, highlighting a female predominance of 89.99% and a mean symptom onset at 33 years. The clinical spectrum of cerebrovascular involvement presented varied symptoms, most notably dizziness, with significant incidences of ischemic events and bilateral stenosis primarily affecting the carotid and subclavian arteries. The most common type of TA was Type V, affecting 40% of patients studied. Endovascular treatment had a 95% initial success rate, with a 67% restenosis rate. Surgical treatment was successful in 84% of cases, but 21% had notable post-operative complications. Similar to the endovascular population, those treated with stand-alone conservative therapy saw a 93% initial remission rate with 52% having relapsed. Assessing the disease activity of TA is crucial when planning vascular intervention due to its significant impact on treatment outcomes. Despite its greater initial invasiveness, surgical interventions showed lower restenosis rates compared to either endovascular interventions or standalone conservative management. We emphasize advancements in TA management and the pressing need for continued research into diagnostic and treatment protocols for improved patient outcomes.

Interleukin 6 Levels and Disease Activity in Takayasu Arteritis: A Systematic Review With Meta-analysis.

Various studies have suggested interleukin 6 (IL-6) as a potential biomarker for detecting disease activity in Takayasu arteritis. A systematic review and meta-analysis was performed to assess differences in IL-6 levels in patients with active (aTA) and inactive Takayasu arteritis (iTA), as well as healthy controls (HCs), using validated activity scores. Study quality and the risk of bias were assessed using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and the Newcastle-Ottawa and Joanna Briggs checklist, respectively. For the meta-analysis, we pooled the raw mean IL-6 levels in each group and then estimated and pooled the crude mean differences between the groups. We applied a random-effects model in all analyses. Of the 93 eligible articles, 10 were included after removing duplicates and studies that met the exclusion criteria. Overall, 1825 patients with a mean age ranging from 24 to 40.6 years were included. The pooled levels of IL-6 increased depending on disease activity as follows: HCs: 3.08 (95% confidence interval [CI], 0.88-5.28), iTA: 7.21 (3.61-10.82), and aTA: 22.67 (12.44-32.91) pg/mL. Patients with aTA had higher IL-6 levels than HCs (21.52 [95% CI, -0.43 to 43.47]) and those with iTA (16.69 [95% CI, 5.32-28.06]), whereas IL-6 levels were not different between HCs and patients with iTA (3.62 [95% CI, -13.18 to 20.42]). Interleukin 6 levels are significantly increased in patients with aTA compared with those with iTA and HCs but not in patients with iTA compared with HCs. More studies are needed to establish the IL-6 cutoff value for assessing disease activity.

Metabolic inflammatory volume and total inflammatory glycolysis: novel parameters to evaluate PET-CT disease activity in Takayasu arteritis.

To evaluate diagnostic accuracy for active Takayasu arteritis (TAK) for two novel 18F-fluorodeoxyglucose PET-CT parameters, the inflammatory volume (MIV) and total inflammatory glycolysis (TIG), to quantitate volume of metabolically-active arterial tissue. From a cohort of TAK (n = 36, 35 immunosuppressive-naïve), images of PET-CTs were reviewed for mean and maximum standardized uptake value (SUVmean and SUVmax), target-to-blood pool ratio (TBR), target-to-liver ratio (TLR), and PET Vasculitis Activity Score (PETVAS). Regions of interest were drawn to semiautomatically calculate MIV in areas of 18F-fluorodeoxyglucose uptake ≥ 1.5 SUVmean after excluding physiological tracer uptake. TIG was calculated by multiplying MIV with SUVmean. PET-CT parameters, ESR, CRP, and clinical disease activity scores were compared against the gold standard of physician global assessment of disease activity (PGA, active/inactive). Using dichotomized cut-offs for active TAK at SUVmax (≥ 2.21), SUVmean (≥ 1.58), TBR (≥ 2.31), TLR (≥ 1.22), PETVAS (various cut-offs), ESR (≥ 40mm/hour), and CRP (≥ 6mg/L), the novel indices MIV (≥ 1.8) and TIG (≥ 2.7) performed similar [area under the receiver operating characteristics curve (AUC) 0.873 for both] to SUVmax (AUC 0.841) and SUVmean (AUC 0.851), and better than TBR (AUC 0.773), TLR (AUC 0.773), PETVAS [≥ 5.5 (AUC 0.750), ≥ 10 (AUC 0.636), ≥ 15 (AUC 0.546)], ESR (AUC 0.748), or CRP (AUC 0.731). MIV and TIG had similar agreement with PGA or CRP as with SUVmax or SUVmean, and better agreement than TBR, TLR, or PETVAS cut-offs. MIV and TIG performed similarly, therefore, are viable alternatives to existing PET-CT parameters to assess TAK disease activity in this preliminary report. Key Points • MIV and TIG performed similar to SUVmax and SUVmax for disease activity assessment in TAK. • MIV and TIG distinguished active TAK better than TBR, TLR, PETVAS cut-offs, ESR, or CRP. • MIV and TIG had better agreement with PGA or CRP than TBR, TLR, or PETVAS cut-offs.

Longitudinal Characterization of Vascular Inflammation and Disease Activity in Takayasu Arteritis and Giant Cell Arteritis: A Single-Center Prospective Study.

To examine and compare disease activity over time in giant cell arteritis (GCA) and Takayasu arteritis (TAK) using multimodal assessment combining clinical, laboratory, and imaging-based testing. Patients with GCA or TAK were enrolled into a single-center prospective, observational cohort at any point in the disease course. Patients underwent standardized assessment, including 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) at enrollment and follow-up visits. Each FDG-PET finding was subjectively interpreted as active or inactive vasculitis. Global arterial FDG uptake was quantified by the PET Vascular Activity Score (PETVAS). Patients were stratified by disease duration at enrollment (0-2 years; 2-5 years; >5 years). Fisher exact and Mann-Whitney U tests, Spearman's correlation, and linear regression were used for statistical analyses. A total of 126 patients with large vessel vasculitis (GCA=50; TAK=76) were evaluated across 319 visits. Clinical disease activity was present in 33% of patients in the second to fifth year of disease and in 24% of patients evaluated >5 years after diagnosis. Active vasculitis by PET was observed in 66% of patients in years 2 to 5 after diagnosis and in 50% of patients enrolled >5 years into disease. PETVASs were consistently higher in GCA than TAK in the early and later phases of disease and significantly decreased over time in GCA but not TAK. Correlations between clinical, laboratory, and imaging findings were complex and varied with disease duration. Disease activity in GCA and TAK is common throughout the disease course. Patterns of vascular PET activity at diagnosis and later in disease differ between GCA and TAK.

Spontaneous delayed expansion of self-expanding stents in stenotic arteries in Takayasu arteritis.

PURPOSE Despite frequent use of self-expanding stents (SES) in treating obstructive arterial lesions in Takayasu arteritis (TA), spontaneous delayed stent expansion (SDSE) in TA remains unstudied. This study aimed primarily to document and quantify SDSE and secondarily to determine factors that might be associated with this process. METHODS Consecutive TA patients with obstructive arterial lesions undergoing routine percutaneous intervention involving SES use (sized 1:1 with normal vessel diameter but dilated only to 4mm/5mm) were recruited prospectively. Final stent diameters obtained were measured at 1cm intervals along the length of the stent using fluoroscopic images and an indwelling marker catheter. At angiographic follow-up, stent diameters were measured again in identical fashion. Interval change in stent diameter at each point was averaged for each stent. In a small sub-study intravascular ultrasound was used at follow-up to obtain potential mechanistic insights. RESULTS Seventeen TA patients (age 33 ± 13 years, 15 female) had 22 arterial obstructive lesions (16 occlusions, 18 subclavian) treated with one SES each. Follow-up obtained in all patients after 8.7 ± 3.8 months (range 3-18 months) showed interval increase in mean stent diameter of 1.6 ± 0.5 mm, range 0.7-2.8 mm (P < 0.001); 36% of stents achieved 100% of the nominal diameter at follow-up, while 90% of stents achieved ≥90%. The degree of SDSE did not correlate with the segment of artery stented or with TA disease activity at baseline. Intravascular ultrasound in four lesions showed that SDSE was associated with positive medial-adventitial remodelling and that neointimal hyperplasia occurs concurrently, causing in-stent luminal narrowing. CONCLUSION SDSE, to diameters equal or close to nominal, occurs in all stenotic TA lesions treated with SES. The degree of SDSE does not correlate with the segment of artery stented or with TA disease activity at baseline. Preliminary results suggest that the mechanism by which SDSE is accommodated by the arterial wall is by positive medial-adventitial remodelling.

Might IgA be a Biomarker of Disease Activity in Takayasu Arteritis?

This case report highlights the need to increase the number of humoral markers used to assess disease course in Takayasu arteritis (TA).IgA may be considered a biomarker of TA disease activity.Serum IgA levels may be helpful to identify TA patients not responding to traditional therapy.

Ultrasonography and contrast-enhanced ultrasound for activity assessment in 115 patients with carotid involvement of Takayasu arteritis.

To evaluate the efficacy of ultrasound and contrast-enhanced ultrasound (CEUS) in disease activity assessment of Takayasu arteritis (TA) with carotid involvement. This is a cohort study of 115 patients of TA with carotid involvement. We investigated correlations between clinical data, sonographic features, and CEUS enhancement at the site most prominent lesion of each patient. Disease activity was assessed by the National Institute of Health Kerr criteria. Sonographic findings were compared with follow-up examinations. CEUS was repeated after a 3-7 months interval in 35 patients to evaluate change of CEUS enhancement after treatment. Extensiveness of CEUS enhancement at most prominent carotid lesions had significant correlations with disease activity by the Kerr criteria (P < .001). The specificity of extensive enhancement for indicating active disease was 95%, while sensitivity was 67%. Patients with active disease showed greater arterial wall thickness and more prominent reduction of arterial wall thickness after treatment. Most of the patients (68%) with subsided active disease after treatment featured decrease of CEUS enhancement. Extensiveness of enhancement by CEUS and arterial wall thickness by ultrasonography may be useful markers for initial and follow-up assessment of disease activity of TA with common carotid artery involvement.

P295 Establishing adenosine deaminase 2 activity in a cohort of patients with large vessel vasculitis

Abstract Background/Aims Deficiency of adenosine deaminase 2 (DADA2) leads to a broad phenotype; some patients develope vasculitis and strokes, and others have predominantly haematological manifestations. Small, medium and large vessel vasculitis has been described. In contrast, plasma ADA2 activity is elevated in inflammatory conditions including systemic lupus erythematosus and systemic juvenile idiopathic arthritis with macrophage activation syndrome. The role of ADA2 and how its deficiency associates with the vasculitides is not well understood. Using a well-characterised large vessel vasculitis cohort, we sought to establish the potential role of ADA2 activity. Methods ADA2 activity was measured in adults with Takayasu arteritis (TA), large vessel giant cell arteritis (LV-GCA), intracranial vasculitis (IV) and healthy control (HC) subjects using a coupled spectrophotometric assay. Plasma from 11 patients with genotyped DADA2 and 10 patients heterozygous for pathogenic variants in ADA2 were used to define thresholds for deficiency and carrier status respectively (DADA2 activity 0 - 0.90 U/L, ADA2 carrier activity 2.02 - 10.62 U/L). Activity levels above the upper limit of normal (ULN) were defined as &amp;gt; 99th percentile of the HC activity (30.3U/L). To assess potential associations with TA disease status, ADA2 was measured prospectively in matched active and remission samples. TA disease activity was determined as active, grumbling or stable using clinical and radiological features, physician impression, CRP, ESR and Indian Takayasu clinical Activity Score (ITAS). Results No patients had deficient ADA2 activity while 7 subjects had activity within the carrier range (1 HC [1.9%], 5 TA [3.7%], 1 LV-GCA [2.3%]). Compared to HC levels (17.43 [14.11 - 20.78] U/L), activity in the TA group was significantly increased (TA 19.68U/L, p = 0.0061), while LV-GCA and IV were not significantly different. In 20 cases, activity exceeded the ULN; 16 TA (11.9%, p = 0.044; 4 active, 2 grumbling, 10 stable) and 4 LV-GCA (9.1%, ns). In TA, there was a positive correlation between ADA2 activity and ESR (Spearman R = 0.2863, p = 0.0009) but not with CRP or ITAS score. Subgroup analysis revealed ADA2 activity was most prominently elevated in the stable group relative to HCs (TA stable 20.54 U/L [8.08 - 48.66], median +17.8%, p = 0.0006), but not with active or grumbling disease. Consistent with this, prospective analysis demonstrated a significant increase in ADA2 activity in remission vs active disease (p = 0.024), with activity increasing in 18 (62%) patients achieving remission. Conclusion There were no cases of ADA2 deficiency in this cohort. Consistent with other inflammatory conditions, ADA2 activity was elevated in TA compared to HC subjects. Surprisingly, increased ADA2 activity was linked to stable TA in both cross-sectional and prospective analyses. This may suggest a potential role of ADA2 enzyme activity in vascular repair and regrowth - possibly tying in with known elevated levels of ADA2 activity in growing children. Disclosure A. Porter: None. R. Maughan: None. C. Pericleous: None. A. Kiprianos: None. H. Jee: None. P. Lee: None. T. Youngstein: None. J. Mason: None.

Comparison of Different Thoracic Aortic Wall Characteristics for Assessment of Disease Activity in Takayasu Arteritis: A Quantitative Study with 3.0 T Magnetic Resonance Imaging

Determination of disease activity in Takayasu arteritis (TAK) is crucial for clinical management but challenging. The value of different magnetic resonance imaging (MRI) characteristics for the assessment of disease activity remains unclear. This study investigated the imaging findings of the thoracic aortic wall and elasticity by using a comprehensive 3.0 T MRI protocol. We prospectively enrolled 52 consecutive TAK patients. TAK activity was recorded according to the ITAS2010. All the patients underwent thoracic aortic MRI. The luminal morphology of the thoracic aorta and its main branches were quantitatively evaluated using a contrast-enhanced magnetic resonance angiography (MRA) sequence. The maximum wall thickness of the thoracic aorta, postcontrast enhancement ratio, and aortic wall edema were analyzed in each patient through pre- and post-enhanced T1-weighted and T2-weighted imaging. Pulse-wave velocity (PWV) of the thoracic aorta was calculated using a four-dimensional flow technique. The majority of the 52 patients had type V disease (34.62%, 18/52). Among all the MRI indicators of the thoracic aorta, the area under the curve was the largest for the maximal wall thickness (0.804, 95% confidence interval [CI] = 0.667-0.941). The maximal wall thickness (93.33%, 95% CI = 68.1%-99.8%) exhibited the highest sensitivity with a cutoff value of 3.12 mm. Wall edema (84.00%, 95% CI = 63.9%-95.5%) presented the highest specificity. A positive correlation was noted between PWV and patients' age (r = 0.54, p < 0.001), disease duration (r = 0.52, p < 0.001), and the maximum wall thickness (r = 0.45, p = 0.001). MRI enabled the comprehensive assessment of aortic wall morphology and functional markers for TAK disease activity. Aortic maximal wall thickness was the most accurate indicator of TAK activity. The early phase was superior to the delay phase for aortic wall enhancement analysis for assessing TAK activity.

Beyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases.

Evidence about the relevance of the complement system, a highly conserved constituent of the innate immunity response that orchestrates the elimination of pathogens and the inflammatory processes, has been recently accumulated in many different rheumatologic conditions. In rheumatoid arthritis, complement, mainly the classical pathway, contributes to tissue damage especially in seropositive subjects, with complement activation occurring in the joint. Data about complement pathways in psoriatic arthritis are dated and poorly consistent; among patients with Sjögren syndrome, hypocomplementemia exerts a prognostic role, identifying patients at risk of extra-glandular manifestations. Hints about complement involvement in systemic sclerosis have been recently raised, following the evidence of complement deposition in affected skin and in renal samples from patients with scleroderma renal crisis. In vasculitides, complement plays a dual role: on one hand, stimulation of neutrophils with anti-neutrophil cytoplasmic antibodies (ANCA) results in the activation of the alternative pathway, on the other, C5a induces translocation of ANCA antigens, favouring the detrimental role of antibodies. Complement deposition in the kidneys identifies patients with more aggressive renal disease; patients with active disease display low serum levels of C3 and C4. Even though in dermatomyositis sC5b-9 deposits are invariably present in affected muscles, data on C3 and C4 fluctuation during disease course are scarce. C3 and C1q serum levels have been explored as potential markers of disease activity in Takayasu arteritis, whereas data in Behçet disease are limited to in vitro observations. Pregnancies in women with rheumatologic conditions are still burdened by a higher rate of pregnancy complications, thus the early identification of women at risk would be invaluable. A fine-tuning of complement activation is required from a physiological progression of pregnancy, from pre-implantation stages, through placentation to labour. Complement deregulation has been implicated in several pregnancy complications, such as recurrent abortion, eclampsia and premature birth; low complement levels have been shown to reliably identify women at risk of complications. Given its physiologic role in orchestrating pregnancy progression and its involvement as pathogenic effector in several rheumatologic conditions, complement system is an attractive candidate biomarker to stratify the obstetric risk among women with rheumatologic conditions.

Fecal S100A12 in Takayasu arteritis predicts disease activity and intestinal involvement.

Gastrointestinal involvement in Takayasu Arteritis (TA) requires invasive or expensive diagnostic studies. Instead a fecal biomarker can be used as an initial screening test. In this context, S100A12 is promising as an established biomarker in intestinal inflammation and its role in TA pathogenesis. As such we aimed to test the feasibility of fecal S100A12 as a means of the fecal biomarker in gastrointestinal involvement in TA in this pilot study. Our study population consisted of 30 TA patients and 14 control patients with non-inflammatory arthralgia. Patients with inflammatory or infectious gastrointestinal tract diseases, or used oral antibiotics or NSAIDs for the 3weeks were excluded. Vasculitis involvements were determined with cross-sectional radiologic studies. TA disease activity was evaluated per Indian Takayasu's Activity Score (2010) criteria and vascular involvements were classified according to Numano classification. ELISA test was used to determine fecal S100A12 levels. Fecal S100A12 levels were higher in TA patients when compared to the controls (37.9ng/ml vs. 12.5ng/ml p = 0.038). ESR and CRP levels were also higher in the TA group, however not correlated with fecal S100A12. Among TA patients, fecal S100A12 levels were higher inactive ones with ITAS2010 > 1 (72.9ng/ml vs. 16.7ng/ml p = 0.016) correlated with total ITAS2010 scores. (R = 0.52 p = 0.003). TA patients with abdominal symptoms had higher fecal S100A12 levels when compared to the remaining TA population (327.8ng/ml vs. 28.0ng/ml p = 0.003). However, fecal S100A12 levels in patients with or without mesenteric vessel involvement did not differ. Fecal S100A12 shows promise as a fecal biomarker to screen intestinal ischemia and inflammatory bowel disease in TA patients.

The study of novel inflammatory markers in takayasu arteritis and its correlation with disease activity

ObjectivesCurrently, erythrocyte sedimentation rate (ESR) and highly sensitive serum C-reactive protein (hsCRP) levels are used to monitor disease activity and guide therapy in Takayasu Arteritis (TA). However, non-specificity of these markers suggests the need for novel biomarkers. In this pilot study, we explore the role of novel biomarkers for evaluating disease activity in TA. MethodsA total of 40 patients with TA were divided into active and stable disease groups. Disease activity was assessed according to the National Institutes of Health criteria proposed by Kerr et al. Routine blood investigations were obtained and serum tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-18, ESR, hsCRP levels and NLR (neutrophil to lymphocyte ratio) were assayed at baseline and after 6 months. ResultsAmong the 40 patients enrolled, 18 were classified as active while 22 were stable at baseline and with a similar pattern at 6 months. Along with ESR and hsCRP, IL-6 and IL-18 levels were significantly higher in the active disease group than in the stable disease group (p < 0.005). The levels of other novel biomarkers (IL-1, TNF-α) and NLR were not significantly higher in active disease group. ConclusionSerum IL-6 and IL-18 levels correlates well with disease activity in TA which suggests their important role in disease pathogenesis and may be helpful in guiding and monitoring therapy in active TA patients.

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

AimsTo examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.Methods and resultsPCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P < 0.0001; PAAT: P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P < 0.0001) and was higher in active vs. inactive TAK (P = 0.002). mPCAT density above −74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97–1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.ConclusionsPCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.

A novel model to assess disease activity in Takayasu arteritis based on 18F-FDG-PET/CT: a Chinese cohort study.

To investigate the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in assessing disease activity in Takayasu arteritis (TA). Ninety-one patients with TA were recruited from a Chinese cohort. Clinical data, acute-phase reactants and 18F-FDG-PET/CT findings were simultaneously recorded. The value of using 18F-FDG-PET/CT to identify active disease was evaluated, using ESR as a reference. Disease activity assessment models were constructed and concordance index (C-index), net reclassification index (NRI), and integrated discrimination index (IDI) were evaluated to compare the benefits of the new modes with ESR and the Kerr score. In total, 64 (70.3%) cases showed active disease. Higher levels of ESR and CRP, and lower IL-2 receptor (IL-2R) levels were observed in active cases. 18F-FDG-PET/CT parameters measured by determining the standard uptake value (SUV), including SUVmean, SUVratio1, SUVratio2, sum of SUVmean and sum of SUVmax, were significantly higher in active disease groups. The C-index threshold of ESR to indicate active disease was 0.78 (95% CI: 0.69, 0.88). The new activity assessment model combining ESR, sum of SUVmean and IL-2R showed significant improvement in C-index over the ESR method (0.96 vs 0.78, P < 0.01; NRI 1.63, P < 0.01; and IDI 0.48, P < 0.01). The new model also demonstrated modest superiority to the Kerr score assessment (0.96 vs 0.87, P = 0.03; NRI 1.19, P < 0.01; and IDI 0.33, P < 0.01). A novel 18F-FDG-PET/CT-based method that involves combining the sum of SUVmean with ESR score and IL-2R levels demonstrated superiority in identifying active TA compared with conventional methods.

Potential Role of Macrophage Phenotypes and CCL2 in the Pathogenesis of Takayasu Arteritis.

ObjectivesTo investigate vascular macrophage phenotype as well as vascular and peripheral chemokine (C-C motif) ligand 2 (CCL2) expression during different stages of disease progression in patients with Takayasu Arteritis (TA).MethodsIn this study, 74 patients with TA and 50 controls were recruited. TA disease activity was evaluated with Kerr scores. Macrophage phenotype and CCL2 expression were examined by immunohistochemistry in vascular specimens from 8 untreated and 7 treated TA patients, along with 4 healthy controls. Serum CCL2 were quantified by enzyme-linked immune-absorbent assay from TA patients at baseline (n=59), at 6-months (n=38), and from 46 healthy volunteers. Vascular macrophage phenotype, vascular CCL2 expression and serum CCL2 levels during different stages, as well as the relationship between serum CCL2 and disease activity or other inflammatory parameters (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin 6 (IL-6)) were investigated.ResultsIn untreated patients, vascular M1 macrophages and CCL2 showed increased expression, mainly in the adventitia. In contrast, in treated patients, vascular adventitial M1 and CCL2 expression were decreased, while vascular medial M2 macrophages and CCL2 levels were increased. Distribution of macrophages and CCL2 was consistent within the TA vascular lesions regardless of the disease stage. Furthermore, peripheral CCL2 was elevated in patients with TA (TA: 160.30 ± 120.05 vs. Control: 65.58 ± 54.56 pg/ml, P < 0.001). CCL2 levels were found to correlate with ESR, CRP, and IL-6 (all R values between 0.55 and 0.6, all P < 0.001). Receiver operating curve analysis demonstrated that CCL2 (at the cut-off value of 100.36 pg/ml) was able to predict disease activity (area under the curve = 0.74, P = 0.03). Decrease in CCL2 level was observed in patients with clinical remission (CR), but not in patients without CR, after 6 months of treatment (CR patients: baseline 220.18 ± 222.69 vs. post-treatment 88.71 ± 55.89 pg/ml, P = 0.04; non-CR patients: baseline 142.45 ± 104.76 vs. post-treatment 279.49 ± 229.46 pg/ml, P = 0.02).ConclusionsMacrophages contribute to vascular pathological changes in TA by undergoing phenotype transformation. CCL2 is an important factor for recruiting macrophages and a potential biomarker for disease activity.

Update on pregnancy in Takayasu arteritis-A narrative review.

Takayasu arteritis (TA) is a chronic, idiopathic large-vessel vasculitis that affects women of reproductive age, and has significant maternal and fetal implications. Although there are contrasting data on the effect of TA on fertility, most studies have shown that fertility outcomes remain unaffected. The disease activity of TA usually either remains stable or decreases during pregnancy. The important fetomaternal complications are maternal hypertension, pre-eclampsia, prematurity, and intrauterine growth restriction. To reduce maternal and fetal morbidity, controlling the disease before conception is important. This review article discusses the various implications, challenges, and medical and endovascular management of TA during pregnancy.

Elevated chemokines concentration is associated with disease activity in Takayasu arteritis

BackgroundChemokines were seldom investigated in Takayasu arteritis (TA) patients. This study aimed to evaluate the plasma levels of chemokines and their association with disease activity, including C-C chemokine ligand (CCL) 2, CCL3, CCL11, CCL20, C-X-C chemokine ligand (CXCL) 8 and CXCL10. MethodsChemokines were measured in 85 TA patients, and 28 age- and gender-matched healthy controls. The disease activity of these TA patients was assessed according to the National Institute of Health (NIH) criteria. The relationship between the plasma levels of chemokines and disease activity was analyzed. ResultsAmong the 85 TA patients, 24 (28.2%) patients had active disease according to the NIH criteria. Significantly increased levels of CCL2, CCL3, CCL20, CXCL8 and CXCL10 were observed in TA patients when compared to healthy controls, while increased levels of CCL2, CCL20, CXCL8 and CXCL10 in TA patients with active disease when compared to those with inactive disease (all p < 0.05). The plasma cut-off values of CCL2, CCL20, CXCL8 and CXCL10 were 309.6 pg/ml, 131.4 pg/ml, 4.7 pg/ml, and 282.1 pg/ml, which maximized the ability of disease activity assessment and had a sensitivity/specificity of 66.7%/67.2%, 54.2%/77.1%,70.8%/72.1%,83.3%/54.1%, respectively (p < 0.05). Among patients with negative erythrocyte sedimentation rate, C-reactive protein or high-sensitivity C-reactive protein, CCL2, CCL20, CXCL8, and CXCL10 still had a high-sensitivity to recognize patients in the active phase. ConclusionsThis study showed that the expression level of CCL2, CCL20, CXCL8 and CXCL10 was elevated in active TA patients, indicating that these chemokines might act as potential biomarkers in evaluating the disease activity.

Serum C1q concentration is associated with disease activity in Chinese Takayasu arteritis patients: A case-control study.

BackgroundC1q is a crucial component of the classical complement pathway. This study is the first to assess the association between disease activity and serum levels of C1q in Chinese Takayasu arteritis (TA) patients.MethodsSerum C1q levels in 198 TA patients and 154 healthy controls were assessed, and the relationship between serum C1q levels and indices of TA disease activity was analyzed. Moreover, we examined the correlation between serum C1q levels and two traditional inflammatory biomarkers; erythrocyte sedimentation rate (ESR) and hypersensitive CRP (hs‐CRP).ResultsSerum C1q levels were increased in TA patients compared with healthy controls (P = .008). TA patients with active disease had higher levels of serum C1q than patients who had inactive disease (P < .0001). In addition, treatment‐naïve patients had higher serum C1q levels than those who had been treated with corticosteroids or at least one immunosuppressant (P = .001). Furthermore, a positive correlation between serum C1q levels and traditional inflammatory biomarkers in TA patients was found. The role of C1q in assessing disease activity was studied, and the area under the receiver operating characteristic curve (AUC) of C1q for predicting active disease was 0.752, and a serum cutoff value of 167.15 mg/L C1q maximized the ability of disease activity assessment, with a sensitivity/specificity of 77.80%/64.90%. When the three indicators (C1q, ESR, and hs‐CRP) were combined, the AUC increased to 0.845, and the sensitivity to 84.40%.ConclusionsThe serum C1q is associated with the disease activity of TA and the combination of three indicators (C1q, ESR, and hs‐CRP) increases the sensitivity of disease activity assessment.

Circulatory histidine levels as predictive indicators of disease activity in takayasu arteritis.

Quantitative assessment of disease activity is important for effective management of patients with autoimmune inflammatory diseases (AIDs) including Takayasu arteritis (TA). Histidine supplementation alleviates inflammation and has strong anti-oxidative effects as well. The present study aims to evaluate the diagnostic potential of circulatory histidine for predicting disease activity in TA. The serum metabolic profiles on 98 TA-patients and 77 normal controls (NC) samples were measured at high-resolution 800MHz NMR spectrometer employing standard 1D-1H-CPMG NMR experiments. The NMR spectral data were processed and concentrations of histidine and other circulatory metabolites were estimatedwith respect to formate (as an internal reference) andcomparedusing ANOVA based on Tukey's multiple comparison test and statistical significance was considered at P-value<0.05. The correlations of histidine with plasma CRP and ESR levels were evaluated using Spearman-r method. Data were expressed as median (interquartile-range [IQR]). Histidine levels were significantly decreased in active TA patients (23.90; IQR:16.10) compared to both inactive TA patients (35.50, IQR:24.30) and NC (42.80, IQR:22.10), whereas there was no significant difference between inactive TA and NC. For TA patients, the histidine levels correlated negatively with clinical markers of inflammation, that is, ESR (r=-0.19, P<.078) and with the CRP (r=-0.26, P<.013). Further, the receiver-operating-characteristic (ROC) curve analysis was performed to test the diagnostic potential of histidine for differentiating active from inactive disease. The area under the ROC curve (AUROC) value equal to 0.65 [95% CI=0.54-0.76] revealed its moderate discriminatory ability. Compared to other circulatory metabolites, the discriminatory performance of histidine was also found to be in the moderate range (highest AUROC-value of 0.76 was found for glutamine-to-glucose ratio (QGR). The study demonstrated the altered circulatory histidine levels in TA patients that may serve as a surrogate marker for improving the diagnostic screening of active and inactive TA patients.

Serum complement 3 is a potential biomarker for assessing disease activity in Takayasu arteritis

BackgroundTakayasu arteritis (TA) is a rare disease, lacking convenient and feasible biomarkers to identify disease activity. We aimed to evaluate the value of complements in distinguishing active TA.MethodsConsecutive patients were enrolled from the prospective East China TA cohort from April 2008 to June 2019. Patients were divided into two groups according to their baseline Kerr score. The value of complements and other biomarkers in identifying disease activity were analysed with cluster analysis, ROC curves, and combined tests. An independent group of patients from July 2019 to December 2019 were employed to validate the results.ResultsOf the enrolled 519 patients, 406 (72.2%) cases were identified as active disease. Higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), and complement 3 (C3) levels were observed in the active group. Elevated C3 (≥ 1.085 g/L) had a high value to identify active TA with a sensitivity of 69.9%, specificity of 66.7%, and AUC of 0.715. Combining the CRP (≥ 10.65 g/L; sensitivity, 50.7%; specificity, 82.4%) and C3, the sensitivity could be improved to 85.1% in parallel test and the specificity could be improved to 94.1% in serial test. Validation was further performed to confirm the value of C3 for disease activity assessment. The accuracy of the parallel test of CRP and C3 in external validation with independent 53 TA cases was 72.73% with the AUC of 0.721.ConclusionElevated C3 could effectively evaluate the disease activity of TA, and C3 combining with CRP could further improve the disease activity evaluation.