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Objective: To identify and validate, using computer-driven methods, patterns of arterial disease in Takayasu arteritis (TAK) and giant cell arteritis (GCA)., Methods: Patients with TAK or GCA were studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American cohort. Case inclusion required evidence of large-vessel involvement, defined as stenosis, occlusion, or aneurysm by angiography/ultrasonography, or increased 18 F-fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) in at least 1 of 11 specified arterial territories. K-means cluster analysis identified groups of patients based on the pattern of arterial involvement. Cluster groups were identified in the DCVAS cohort and independently validated in the North American cohort., Results: A total of 1,068 patients were included (DCVAS cohort: TAK = 461, GCA = 217; North American cohort: TAK = 225, GCA = 165). Six distinct clusters of patients were identified in DCVAS and validated in the North American cohort. Patients with TAK were more likely to have disease in the abdominal vasculature, bilateral disease of the subclavian and carotid arteries, or focal disease limited to the left subclavian artery than GCA (P < 0.01). Patients with GCA were more likely to have diffuse disease, involvement of bilateral axillary/subclavian arteries, or minimal disease without a definable pattern than TAK (P < 0.01). Patients with TAK were more likely to have damage by angiography, and patients with GCA were more likely to have arterial FDG uptake by PET without associated vascular damage., Conclusion: Arterial patterns of disease highlight both shared and divergent vascular patterns between TAK and GCA and should be incorporated into classification criteria for large-vessel vasculitis., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Objectives: To develop and replicate, using data-driven methods, a novel classification system in Takayasu's arteritis based on distribution of arterial lesions., Methods: Patients were included from four international cohorts at major academic centres: India (Christian Medical College Vellore); North America (National Institutes of Health, Vasculitis Clinical Research Consortium and Cleveland Clinic Foundation). All patients underwent whole-body angiography of the aorta and branch vessels, with categorization of arterial damage (stenosis, occlusion or aneurysm) in 13 territories. K-means cluster analysis was performed to identify subgroups of patients based on pattern of angiographic involvement. Cluster groups were identified in the Indian cohort and independently replicated in the North American cohorts., Results: A total of 806 patients with Takayasu's arteritis from India (n = 581) and North America (n = 225) were included. Three distinct clusters defined by arterial damage were identified in the Indian cohort and replicated in each of the North American cohorts. Patients in cluster one had significantly more disease in the abdominal aorta, renal and mesenteric arteries (P < 0.01). Patients in cluster two had significantly more bilateral disease in the carotid and subclavian arteries (P < 0.01). Compared with clusters one and two, patients in cluster three had asymmetric disease with fewer involved territories (P < 0.01). Demographics, clinical symptoms and clinical outcomes differed by cluster., Conclusion: This large study in Takayasu's arteritis identified and replicated three novel subsets of patients based on patterns of arterial damage. Angiographic-based disease classification requires validation by demonstrating potential aetiological or prognostic implications., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2019. This work is written by US Government employees and is in the public domain in the US.)

Objective: Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis., Methods: Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis., Results: We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B., Conclusion: Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis., (© 2015, American College of Rheumatology.)

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8))., (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA)., Methods: Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification., Results: Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ≤55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA., Conclusions: Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) have been considered distinct disorders based on their clinical features, age of onset, and ethnic distribution. However, on closer examination, these disorders appear more similar than different. The histopathology of arterial lesions in these diseases may be indistinguishable. Imaging studies have revealed large vessel inflammation in at least 60% of patients with GCA. We questioned whether the distinctions between these diseases might in part be an artifact due to bias in gathering historical and physical data. We postulated that signs and symptoms of GCA and polymyalgia rheumatica occur in patients with TAK but have been under-reported as a result of this bias.We performed a retrospective review of 75 patients with TAK and 69 patients with GCA (per American College of Rheumatology criteria). Signs and symptoms attributable to disease within the year before and following diagnosis, treatment and interventional outcomes, and mortality were recorded using a standardized database. All cases were evaluated by a single physician, using identical history and physical examination forms for patients with both diseases.Patients were predominantly female (TAK 91%, GCA 82%) and white (TAK 88%, GCA 95%). New headache was a presenting symptom in 52% of TAK and in 70% of GCA patients. All TAK patients underwent vascular imaging studies and were demonstrated to have large vessel abnormalities. However, only a subset of patients with GCA (43/69, 62%) was similarly studied. Among this group, 73% of GCA patients had at least 1 arterial lesion identified. In both TAK and GCA, the most common sites of involvement were the aorta (TAK 77%, GCA 65%) and subclavian (TAK 65%, GCA 37%) arteries. Compared to patients with TAK, patients with GCA had a greater prevalence of jaw claudication (GCA 33%, TAK 5%), blurred vision (GCA 29%, TAK 8%), diplopia (GCA 9%, TAK 0%), and blindness (GCA 14%, TAK 0%).Symptoms, signs, and imaging abnormalities that are characteristic of GCA or TAK are often present, albeit in differing frequencies, in both disorders. These findings lend support to the hypothesis that these diseases may not be distinct entities, but represent skewed phenotypes within the spectrum of a single disorder. Differences in frequencies of manifestations may reflect a significant bias in how data are gathered for patients with each disease, as well as the influence of vascular and immunologic senescence.

Takayasu arteritis (TA) is a form of idiopathic large vessel vasculitis that predominantly affects women of reproductive age. Although TA is a rare disease, the interpretation of longitudinal data from several countries provides new insights into the clinical course and outcomes in TA across different racial and ethnic groups. Contemporary studies belie prior perceptions of TA as a disease with a self-limited, benign course. We now recognize this disease as one that often relapses, leaves the patient chronically dependent on glucocorticoids for disease control, and frequently leads to disability. Limited data suggest that the targeted inhibition of tumor necrosis factor (TNF) might be an effective therapy for TA.

Objective: To describe the clinical, laboratory, and radiographic manifestations of Takayasu arteritis (TA) in a cohort from the US, evaluate the response to interventions, remission and relapse rates, and disease progression, and compare these observations with those from other cohorts in the US, Japan, India, Italy, and Mexico., Methods: Seventy-five patients were retrospectively studied using a uniform database that included clinical, laboratory, and imaging data. Vascular imaging studies were performed at least yearly to monitor disease progression., Results: Common manifestations at disease onset included loss or asymmetry of pulses (57%), limb blood pressure discrepancy (53%), and bruits (53%). Eleven percent of patients were asymptomatic prior to disease diagnosis. Initial angiographic studies showed aortic abnormalities in 79% of patients and frequent involvement of the subclavian (65%) and carotid (43%) arteries.Ninety-three percent of longitudinally followed patients attained disease remission of any duration, but only 28% sustained remission of at least 6 months' duration after prednisone was tapered to <10 mg daily. Both angioplasty and vascular surgery were initially successful, but recurrent stenosis occurred in 78% of angioplasty and 36% of bypass/reconstruction procedures. More than two-thirds of patients had difficulty performing routine daily activities and approximately one-fourth of all patients were unable to work. Our cohort was similar to the National Institutes of Health, Italian, Japanese, and Mexican cohorts in terms of the predominance of female subjects and disease manifestations, but differed from the Indian cohort in that the latter group had a higher frequency of male subjects, abdominal aorta and renal artery involvement, and hypertension., Conclusion: Although improvement of symptoms in TA usually follows glucocorticoid therapy, relapses usually occur with dosage reduction. Attempts to restore vascular patency are often initially successful, but restenosis occurs frequently. Chronic morbidity and disability occur in most patients with TA in the US.

Takayasu arteritis (TA) is a rare, chronic inflammatory disease that mainly affects the aorta and its primary branches. Initially described in young women from the Far East, it has become evident that TA is found worldwide, in both genders, and in a broader age range of patients than previously appreciated. Although the pathogenesis of TA remains unknown, current evidence suggests an autoimmune etiology. The immune response to pathogen exposure has been purported as a potential etiological factor, and current investigations continue to explore this hypothesized trigger of disease. Prior cohort studies document the relapsing, refractory nature of TA and the limitations of currently utilized therapies, although advances in immunosuppressive therapy may lead to better outcomes in patients with TA. Furthermore, newer diagnostic imaging modalities have provided a more comprehensive picture of this disease, and may aid in earlier diagnosis and better surveillance of disease activity and response to therapy. INSET: Key issues. [ABSTRACT FROM AUTHOR]