Background: Takayasu arteritis (TAK) is a heterogeneous large-vessel vasculitis, and existing anatomical classifications provide limited prognostic information. Methods: In this multicenter cohort study, 338 patients with TAK from three tertiary centers were included. Arterial involvement across 18 vascular territories was assessed, and unsupervised hierarchical clustering identified imaging-defined vascular phenotypes. Clinical associations were analysed using multivariable logistic regression, and long-term outcomes were evaluated in 305 patients with follow-up data. Findings: Five vascular phenotypes were identified: Iliac–Cardio–Cerebral (n=39), Abdominal (n=78), Thoracic–Pulmonary (n=89), Vertebral (n=41), and Brachiocephalic (n=91). Outcomes differed significantly across phenotypes, including all-cause mortality (log-rank p=0.003) and cumulative adverse events (log-rank p<0.001). The Iliac–Cardio–Cerebral phenotype had the highest risks of mortality (HR=6.9, p<0.0001), total adverse events (HR=2.22, 95% CI 1.24–3.97), and cardiovascular events (HR=4.51, 95% CI 1.83–11.12). The Abdominal, Thoracic–Pulmonary, and Vertebral phenotypes were associated with increased renal, pulmonary, and cerebrovascular events, respectively, whereas the Brachiocephalic phenotype showed the most favourable prognosis. Interpretation: Imaging-defined vascular phenotypes identify distinct risks of organ-specific complications and mortality in TAK. This phenotype-based framework may improve prognostic stratification and support individualized management.

To investigate the role of CD34-high endothelial cells (CD34hi_ECs) and fibroblast growth factor-2 (FGF2) signaling in the pathological vasa vasorum angiogenesis and inflammatory progression of Takayasu arteritis (TAK). Single-cell RNA sequencing (scRNA-seq) and immunohistochemical analyses of aortic walls from three TAK patients and three controls were performed to evaluate CD34hi_ECs and FGF2 expression. Serum cytokines from 48 TAK patients and 24 healthy controls were measured by cytometric bead array. ScRNA-seq of human aortic tissues revealed a marked expansion of CD34hi_ECs in TAK lesions (97.6

Elevated serum ferritin levels predict adverse outcomes in many autoimmune diseases. However, its clinical significance in Takayasu arteritis (TAK) is not clear. This study aimed to evaluate the predictive value of serum ferritin for major adverse cardiovascular events (MACEs) in TAK. A two-center retrospective cohort study was conducted. A total of 189 treatment-naïve TAK patients who underwent serum ferritin testing at baseline were consecutively enrolled and followed longitudinally. The association between serum ferritin levels and adverse events was assessed using survival analyses. Thirty-seven patients (19.6

Leflunomide (LEF) shows promising effect in Takayasu arteritis (TAK), but evidence from randomized controlled trials is lacking. This study aims to investigate the efficacy and safety of LEF versus placebo combined with prednisone for the treatment of TAK. This is a multicenter, randomized, double-blind, placebo-controlled trial at six sites across China, conducting from December 22, 2016, to November 4, 2022. A total of 116 eligible patients were recruited and randomized 1:1 to receive LEF (20 mg/d, p.o.) or matched placebo for 24 weeks, with all patients having initial prednisone of 0.6 mg/kg/d and following a taper starting at week 4. By week 24, patients in the LEF group who did not achieve clinical remission discontinued the study; all other patients (both LEF and placebo groups) received LEF (20 mg/d) from week 25 to week 52. The primary outcome was clinical remission at week 24. Secondary outcomes were time-to-clinical remission, mean prednisone dose at week 24, clinical remission in those who switched to LEF from week 25, disease recurrence and time-to-recurrence, imaging changes, and safety. Fifty-four and 57, 45 and 48 patients were included in LEF and placebo group of modified intention-to-treat (mITT) and per-protocol set (PPS). In mITT set, clinical remission was achieved in 44/54 (81.5

BACKGROUND:Coronary artery vasculitis (CAV) is a relatively rare etiology of coronary artery disease (CAD), which could lead to recurrent complications once treated with coronary stents. However, differentiating between CAV and atherosclerotic CAD is challenging. CASE SUMMARY:Included in this case series were 10 symptomatic patients who were initially considered as having atherosclerotic CAD but were eventually diagnosed with CAV at our center from August 2021 to October 2024. We describe the clinical and imaging characteristics of these patients. DISCUSSION:This case series shows several classic CAV characteristics on coronary computed tomography angiography, raising the awareness of CAV misdiagnosis and highlighting the importance of timely order and dedicated imaging analysis for the diagnosis of CAV. TAKE-HOME MESSAGE:Coronary computed tomography angiography can provide comprehensive information on plaque characteristics, coronary artery wall abnormalities, and pericoronary inflammation, which can help cardiologists and radiologists differentiate between CAV and atherosclerotic CAD.

Previous studies have suggested that granulocyte colony-stimulating factor (G-CSF) treatment may trigger large vessel vasculitis (LVV). However, the role of G-CSF in Takayasu arteritis (TAK), a form of LVV, remains unclear. This study aims to investigate the potential role of G-CSF in TAK. This cross-sectional study included 40 TAK patients who met the 1990 American College of Rheumatology (ACR) classification criteria for Takayasu arteritis and 27 healthy controls (HCs). Group differences and correlations between G-CSF level, clinical parameters, and cytokine profiles were analyzed using appropriate tests. Aortic tissues from TAK patients were also examined for G-CSF expression using immunohistochemistry. G-CSF levels were significantly higher in TAK patients compared to controls (p < 0.0001), but no difference was found between active and inactive TAK. G-CSF levels positively correlated with neutrophil (R = 0.350, p = 0.028) and platelet counts (R = 0.466, p = 0.005). Elevated G-CSF levels were associated with several cytokines, including IL-6 (R = 0.672, p < 0.001), IL-17 (R = 0.692, p < 0.001), and IFN-γ (R = 0.897, p < 0.001). G-CSF may contribute to the inflammatory process and pathogenesis of TAK, offering new perspectives for its diagnosis and treatment.

OBJECTIVE:To validate the performance of the 2022 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for Takayasu arteritis (TAK) in a China cohort and examine its performance in clinical practices. METHODS:Seven hundred seventy-eight patients with TAK and 378 patients with non-TAK were included. The sensitivity, specificity, positive and negative predictive values, accuracy and AUC of the 2022 ACR/EULAR and 1990 ACR criteria were assessed. Furthermore, the Kaplan-Meier curve was used to analyse the impact of high and low scores on prognosis according to the 2022 ACR/EULAR criteria for TAK. RESULTS:In this Chinese cohort, the 2022 ACR/EULAR criteria demonstrated superior performance with a sensitivity of 95.2% (95% CI: 93.4-96.5%), specificity of 95.8% (93.1-97.5%) and an AUC of 0.955 (0.940-0.970), compared with the 1990 ACR criteria, which had a sensitivity of 93.6% (91.6-95.1%), specificity of 92.3% (89.0-94.7%), and an AUC of 0.930 (0.911-0.948). Based on the 2022 ACR/EULAR criteria, false-negative cases had fewer vascular ischaemia symptoms and less affected arterial regions than true positives, while false positives mainly differed in angina and blood pressure. Survival analysis indicated that patients with scores ≥15 had significantly lower overall survival rates than those with scores <15, highlighting the need for increased clinical attention to these patients. CONCLUSION:Compared with the 1990 ACR criteria, the 2022 ACR/EULAR criteria for TAK demonstrate better specificity and sensitivity in real-world clinical practice. The score derived from the 2022 classification criteria is related to the prognosis.

OBJECTIVES:This study aims to analyse the expression profiles, phenotypes, functions and cell-cell communication of various cell subpopulations in the affected aortic tissues of patients with Behçet's syndrome (BS) at the transcriptomic level. METHODS:This study recruited six participants (three with BS and three with atherosclerosis) from Beijing Anzhen Hospital between January 2023 and June 2024, collected their clinical information, and performed single-cell RNA sequencing on aortic tissue specimens using the SeekOne® MM High Flux Single Cell Transcriptome Kit V4.1. The data were analysed with Seurat and Harmony in R, including quality control, cell clustering, differential gene expression analysis, GO and KEGG enrichment analyses, subgroup analyses focusing on specific cell types, and intercellular communication analysis using CellChat v1.6.1. RESULTS:The study identified eight major cell types in aortic tissues, with significant differences in cell proportions between BS patients and controls. Compared with controls, BS patients had increased endothelial cells, fibroblasts and mesenchymal stem cells, while smooth muscle cells decreased. Subgroup analysis revealed significant differences between the BS and control groups in cell subpopulation distribution, enriched pathways and cell interactions. CONCLUSION:Our study revealed cellular and molecular changes in the aortic tissues of patients with BS, laying the foundation for elucidating the pathogenesis of BS and identifying potential therapeutic targets.

Objective The aim of this study was to investigate the predictive value of uric acid (UA) in prognosis of pulmonary artery involvement (PAI) in patients with Takayasu's arteritis (TAK). Methods A total of 166 TAK patients were enrolled in the study, including 76 with PAI and 90 without. Outcomes of 144 TAK patients were followed up and recorded. The possible associations between serum UA levels and incidence of PAI in TAK and PAI-related prognosis of TAK patients were examined using different statistical models. Results The serum UA levels were significantly higher in TAK patient with PAI than TAK patients without PAI. Multivariate logistic regression analysis indicated that serum UA level >= 284.5 umoliL was associated with an increasing incidence of PAI in TAK (OR: 2.108, 95% CI: 1.063 to 4.180; p=0.033). Kaplan-Meier survival analysis showed that TAKpatients with serum UA level >= 328.1 umoliL had a significantly higher cumulative incidence of PAI-related adverse events compared to TAK patients with serum UA level <328.1 umoliL (p=0.008). Multivariate Cox proportional hazard regression analysis revealed that serum UA level >= 328.1 umoliL (HR: 2.595, 95% CI: 1.198 to 5.622; p=0.016) was a PAI-related prognostic risk factor for TAK. Conclusion Elevation of serum UA level was associated with an increasing risk of PAI and PAI-related adverse event in patients with TAK, indicating its potential as a predictor for identification of PAI onset and worsening in TAK patients.

OBJECTIVES:Study the efficacy and safety of mycophenolate mofetil (MMF) combined with methotrexate (MTX) compared to cyclophosphamide (CYC) followed by azathioprine (AZA) to treat active Takayasu arteritis (TAK). METHODS:Adults with active TAK were randomised in a 2:1 ratio to receive oral MMF plus MTX or intravenous CYC followed by oral AZA. All subjects also received high-dose oral glucocorticoids with a predefined taper. The primary endpoint was overall response rate at week 52, defined as achieving a complete response (CR) or partial response (PR). Secondary endpoints included rates of CR and PR at weeks 28 and 52. RESULTS:A total of 111 patients with TAK were enrolled: 74 in the MMF+MTX group and 37 in the CYC/AZA group, with comparable baseline demographic and clinical features. The overall response rates at 28 and 52 weeks were 58.1% and 55.4% in the MMF+MTX group, respectively, higher than 32.4% at both time points in the CYC/AZA group (P = .011 and .022). CR and PR rates at 28 and 52 weeks were also higher in the MMF+MTX group. Relapse occurred in 4 patients in the MMF+MTX group and 2 in the CYC/AZA group. One serious adverse event, neutropenia with fever, occurred in 1 patient in the CYC/AZA group. CONCLUSIONS:Treatment of active TAK with MMF+MTX has more favourable efficacy compared to CYC/AZA. These findings provide evidence to use the combination of MTX and MMF, 2 generally well-tolerated and inexpensive therapies, to treat TAK.

Takayasu arteritis (TAK) is a rare, chronic large-vessel vasculitis. Although CD4⁺ and CD8⁺ T cells are acknowledged drivers of vascular injury in TAK, the gene networks that confer their pathogenicity remain incompletely mapped. This study aimed to integrate bulk RNA-sequencing of peripheral-blood T-cell subsets with single-cell RNA-sequencing of aortic tissue to find mechanistic biomarkers and therapeutic targets for TAK. We performed bulk RNA-sequencing on peripheral-blood CD4⁺ and CD8⁺ T cells from eight treatment-naïve TAK patients and three age matched healthy controls. In parallel, single-cell RNA-sequencing was applied to aortic tissue from three additional TAK patients and three atherosclerotic controls. DEGs were defined at false-discovery rate < 0.05. Functional enrichment used Gene Ontology, KEGG and Reactome. STRING constructed protein–protein interaction networks, and Cell Chat inferred intercellular ligand–receptor communication. Bulk profiling identified 851 DEGs in CD4⁺ and 1 645 DEGs in CD8⁺ T cells. CD4⁺ DEGs were enriched for inflammation, angiogenesis and platelet-activation pathways; CD8⁺ DEGs concentrated on cytokine synthesis, notably interleukin-1 signaling. Both subsets shared enrichment in complement cascade, focal adhesion and extracellular-matrix organization, indicating convergent pro-inflammatory programs. Single-cell analyses delineated dense CD4⁺– CD8⁺ crosstalk within TAK aorta and, relative to atherosclerotic controls, heat-shock protein binding and ubiquitin-ligase activity—hallmarks of heightened protein-homeostasis stress. Four transcriptional regulators—EGR1, KLF4, RHOB and ATF3—were consistently up-regulated in both blood and tissue; EGR1 showed the strongest fold-change and occupied a central hub in protein-interaction and ligand–receptor networks. In peripheral cells EGR1 co-clustered with cytokine-biosynthetic modules, while in tissue its profile mirrored the composite CD4⁺ and CD8⁺ signature, underscoring a unifying role in systemic and local inflammation. Integrated bulk and single-cell transcriptomics reveal both shared and subset-specific signaling landscapes for CD4⁺ and CD8⁺ T cells in TAK. The consistent prominence of EGR1 across compartments nominates this factor as a pivotal molecular switch and attractive therapeutic target. These data furnish a mechanistic framework for precision immune modulation in large-vessel vasculitis.

BACKGROUND:This study aimed to analyze the factors associated with cardiovascular events and develop a prediction model to predict 10-year cardiovascular events probability in patients with Takayasu arteritis (TAK). METHODS:Patients with TAK were prospectively enrolled from 7 clinical centres between July 2013 and March 2021. The Cox proportional hazard regression was used to assess factors associated with cardiovascular events and develop a prediction model. The model performance was measured by Harrell's concordance index (C-index), Brier score, and calibration plots. The nomogram was used to calculate the 10-year cardiovascular events probability. RESULTS:A total of 702 patients (aged 29.2 ± 9.9 years; 623 [88.7%] women) were included. Cardiovascular events were observed in 94 patients (13.4%) after a median follow-up of 67 months (interquartile range [IQR]: 46-99). Elevated erythrocyte sedimentation rate (ESR) at disease onset (hazard ratio [HR], 2.30 [1.47-3.60]), pulmonary hypertension (HR, 1.87 [0.93-3.77]), pulselessness (HR, 1.73 [1.14-2.63]), diagnostic delay ≥ 3 years (HR, 1.63 [1.01-2.65]), aortic regurgitation (HR, 1.61 [1.01-2.56]), and age at diagnosis (HR, 1.05 [1.02-1.07]) independently increased cardiovascular events and were included in the final model. The optimism-corrected C-index and Brier score of prediction model were 0.71 (0.66-0.76) and 0.072, respectively, and the calibration plots suggested good agreement between the observed and predicted probability of cardiovascular events. CONCLUSIONS:Patients with TAK were at high risk of cardiovascular events. Advanced age at diagnosis, diagnosis delayed over 3 years, pulselessness, pulmonary hypertension, aortic regurgitation, and elevated ESR at disease onset were risk factors for cardiovascular events. CLINICAL TRIAL REGISTRATION:JS-2038.

Takayasu arteritis (TAK) is an inflammatory vasculitis that affects the aorta and its primary branches. The pathogenesis of TAK remains elusive, yet identifying key cell types in the aorta of TAK patients is crucial for uncovering cellular heterogeneity and discovering potential therapeutic targets. This study utilized single-cell transcriptome analysis on aortic specimens from three TAK patients, with control data sourced from a publicly available database (GSE155468). Additionally, bulk RNA sequencing was performed on peripheral CD4 + and CD8 + T cells from eight TAK patients and eight matched healthy volunteers. All participants were recruited at Anzhen Hospital, Capital Medical University, China, between January 2020 and December 2023. Single-cell transcriptome analysis identified 11 predominant cell types in aortic tissues, with notable differences in proportions between TAK patients and controls. T cells, B cells, macrophages, smooth muscle cells (SMCs), and fibroblasts exhibited subtype-specific gene expression signatures, with notable changes in interactions between T cells, B cells, and monocyte-macrophages, highlighting their active involvement in the pathogenesis of TAK. Bulk RNA-Seq analysis of peripheral blood T cells from TAK patients showed an upregulation of complement system genes, underscoring the significance of the complement signaling pathway in TAK’s immunopathogenesis. The findings underscore the active involvement of various immune and structural cells in the aortic tissues of TAK patients and reveal the presence of the complement signaling pathway in peripheral blood T cells. These insights are instrumental for identifying novel therapeutic targets and developing robust disease monitoring methods for TAK.

Coronary artery involvement (CAI) is a special but not rare manifestation of Takayasu arteritis (TAK). Granzyme B (GzmB) is a multifunctional protease associated with the immune system and coronary artery disease. However, its role in patients with TAK and CAI remains unclear. This study investigates the role of GzmB(+) cell subsets in TAK. The study included 105 TAK patients and 58 healthy controls. The percentages of different GzmB(+) cells in blood samples were analyzed by flow cytometry. We found that age, age at onset, body mass index, disease duration month, hypertension, and hyperlipidemia were significantly different between TAK patients with and without CAI (P = 0.000, P = 0.038, P = 0.003, P = 0.031, P = 0.039, P = 0.000). The proportions of CD3(+)CD8(+)cells (P = 0.001) and CD3(+)CD4(+)cells (P = 0.000) in GzmB(+) cells were significantly increased, while the proportion of CD3(-)CD56(+)cells (P = 0.001) in GzmB(+) cells was decreased in TAK patients. The proportions of three types of GzmB(+) subsets in lymphocytes (CD3(+)CD4(+)GzmB(+), CD3(+)CD8(+)GzmB(+), CD3(+)CD56(+) GzmB(+)) were higher in TAK patients with CAI compared with those without CAI (P = 0.021, P = 0.007, P = 0.007). The increased proportion of CD3(+)CD8(+)GzmB(+)cells/lymphocytes was an independent risk factor for coronary involvement in TAK (OR = 4.990 [1.766-14.098], P = 0.002). Additionally, patients with a high CD3(+)CD8(+)GzmB(+)cells/lymphocytes ratio had a higher major adverse cardiovascular events rate than those with a low ratio in TAK (P = 0.019). Our results indicate that CD8 cell-derived Gzm B may be a predictor for CAI and major adverse cardiovascular events in TAK patients. Targeting CD3(+)CD8(+)GzmB(+) lymphocytes or using GzmB inhibitors could be a potential therapeutic approach for the treatment of CAI in TAK.

Background: Takayasu arteritis (TA) is associated with an increased risk of developing complicated comorbidities, which can bring both psychological and physical burdens to the patients. Objective: TA is found to carry a high risk of developing depression. This research aimed to investigate the risk factors and prognosis of depression in TA patients. Design: A longitudinal observation cohort was conducted on TA patients with or without depression to explore the clinical characteristics. Methods: In this cohort study, 90 TA patients were split into two groups with or without depression. Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS) in TA patients. TA patients with depression were followed up for at least 3 months. We used multivariate logistic regression analysis to find the risk factors and Kaplan–Meier curve analysis to determine the prognosis. Results: We concluded 90 TA patients in this research, 29 of whom were in depression. Indian Takayasu’s Arteritis Activity Score (ITAS2010) ⩾2 (odds ratio (OR) (95% confidence interval, CI) 26.664 (2.004–354.741), p = 0.013), interleukin-6 (IL-6) (OR (95% CI) 1.070 (1.022–1.121), p = 0.004), prednisone equivalents (OR (95% CI) 1.101 (1.030–1.177), p = 0.005), and carotidynia (OR (95% CI) 5.829 (1.142–29.751), p = 0.034) have been shown independent risk factors for depression in TA patients. We also identified the association between disease remission with the improvement of HADS-D score (Log-rank p = 0.005, hazard ratio (HR) 0.25) and depression (Log-rank p = 0.043, HR 0.28). Conclusion: Aggressive treatment to achieve remission can promote improvement of depression in patients with TA. Screening for depression should also be performed in patients with elevated disease activity, IL-6, glucocorticoid use, and carotidynia.

Cogan's syndrome (CS) is recognized as a form of variable vasculitis. This report presents the case of a middle-aged woman experiencing recurrent coronary artery stenosis, accompanied by a history of non-syphilis keratitis, vestibular auditory symptoms, and venous thrombosis. Positron emission tomography/computed tomography revealed an elevated uptake of (18)F-fluorodeoxyglucose in the subclavian artery, common carotid artery, aortic arch, and thoracic aorta. A diagnosis of Cogan's syndrome was made. The aim of this study was to increase clinicians’ awareness of the vascular manifestations in CS and to emphasize the importance of thorough history taking. CS should be included in the differential diagnosis when patients present with recurrent coronary artery stenosis.

Abstract Objective Recent studies have indicated a potential association between giant cell arteritis (GCA) and diabetes mellitus, encompassing both type 1 diabetes (T1D) and type 2 diabetes (T2D). However, the exact nature of this relationship requires further investigation to be fully elucidated. Methods Genetic links between T1D/T2D and GCA were explored using data from genome-wide association studies available to the public, focusing on populations of European ancestry. We applied a bidirectional mendelian randomization (MR) approach to assess the potential association between these diseases. Confirmatory analyses, including additional datasets and a comprehensive meta-analysis, were utilized. The inverse-variance-weighted (IVW) method was applied to pinpoint heterogeneity and pleiotropy, while subsequent sensitivity analyses aimed to trace the origins of any heterogeneity. Results Initial analysis demonstrated a correlation between T1D and an elevated likelihood of developing GCA (IVW odds ratio = 1.33, with a 95% confidence interval of 1.22–1.46, and a P-value of 9.42E−10). The causal association was verified through four validation datasets and meta-analysis (all P-value < 0.001). However, the reverse MR analysis was unable to detect any genetic basis for the increased risk of T1D due to GCA. Furthermore, we could not establish any causal links between T2D and GCA. Conclusion T1D patients may have a higher risk of developing GCA, whereas an inverse causal relationship was not evident. Furthermore, no causal relationship was detected between T2D and GCA. These insights shed light on the possible pathological mechanisms underlying GCA and may influence the future clinical handling of both T1D and GCA.

Abstract Background The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. Methods We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. Results IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. Conclusions Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.