OBJECTIVE:Takayasu arteritis (TAK)-related stroke and large-artery atherosclerosis (LAA)-related stroke share overlapping clinical features but differ fundamentally in pathophysiology and treatment strategies. Differentiating these two aetiologies remains a diagnostic challenge with critical therapeutic implications. We aimed to compare the clinical profiles, imaging characteristics and outcomes of TAK- versus LAA-related stroke to provide insights for diagnosis and management. PATIENTS AND METHODS:We conducted a multicentre comparative study using nationwide prospective registry cohorts in China. Among 926 patients with TAK, 80 patients with stroke were included. In addition, 372 patients with LAA-related stroke were selected from the China National Stroke Registry-III cohort (n=14 146). Clinical and imaging characteristics, traditional stroke risk factors and outcomes were analysed and compared. Subgroup analyses were performed according to the presence of atherosclerosis in TAK. Propensity score weighting was performed as a sensitivity analysis. RESULTS:Compared with LAA-related stroke, TAK-related stroke was younger, with a strong female predominance and lower prevalence of vascular risk factors and appeared to have a higher proportion of favourable functional outcomes (modified Rankin Scale 0-2: 93.2% vs 72.6%, p=0.0002), although direct comparison was limited by differences in follow-up structure and assessment timing. Furthermore, patients with TAK tended to show distinct imaging features, including predominant extracranial artery involvement and anterior circulation infarctions located in the subcortical/deep white matter. Among patients with TAK-related stroke, those with coexisting atherosclerosis were older, had longer disease duration and had a greater risk of supra-aortic complications and a higher rate of endovascular interventions. CONCLUSIONS:This study highlights distinct clinical and imaging profiles between TAK- and LAA-related strokes. It also provides a comparative analysis of TAK-related stroke with and without atherosclerosis, revealing differences in risk factors, vascular characteristics and intervention needs. These findings provide a descriptive framework that may assist aetiological differentiation and hypothesis generation for future studies.

To assess whether age independently predicts renal function in Takayasu arteritis (TA) patients with abdominal aortic involvemen. This retrospective study included 149 TA patients. Renal function was assessed by estimated glomerular filtration rate (eGFR). Vascular features (severe RAS, aortic plaques) were evaluated via integrated ultrasound and CT angiography. Univariate and multivariate regression analyses identified determinants of eGFR and clinical renal impairment (eGFR < 90 mL/min/1.73m²). Mean age was 33.85 years. Age showed the strongest inverse correlation with eGFR (r = -0.538, p < 0.001). In multivariate analysis, age remained the most robust independent predictor of lower eGFR (standardized β = -0.500, p < 0.001), exceeding the effect of severe RAS (β = -0.143, p = 0.043). The association of aortic plaques with eGFR lost significance after age adjustment. Logistic regression confirmed age as an independent risk factor for renal impairment (adjusted OR = 1.078 per year, 95% CI: 1.036–1.122, p < 0.001). In TA, chronological age is the strongest independent predictor of renal function, surpassing severe RAS. These findings highlight the necessity of incorporating an age-aware perspective into the clinical assessment of renal health in TA, particularly given its typical onset in young adulthood.

OBJECTIVE:This study aimed to explore the pathogenic role of Toll-like receptor 8 (TLR8) in rheumatoid arthritis (RA) and evaluate its potential as a therapeutic target. Using a combination of in vitro and in vivo models, we explored the functional involvement of TLR8 in RA pathogenesis and assessed the efficacy of TLR8 inhibition. METHODS:Gene expression profiles of patients with RA and healthy controls were analyzed to identify up-regulated genes and pathways. In vitro RA models were established using fibroblast-like synoviocytes (FLSs) from patients with RA, human umbilical vein endothelial cells, and peripheral blood mononuclear cells from patients with RA and RA monkeys and to examine TLR8's role in synoviocyte proliferation, angiogenesis, and inflammation. Additionally, the therapeutic efficacy of a TLR8 inhibitor was evaluated in collagen-induced arthritis (CIA) mouse and RA rabbit models. RESULTS:TLR8 is aberrantly overexpressed in patients with RA and shows strong positive correlations with disease activity. Mechanistically, the up-regulation and activation of TLR8 drives RA progression by promoting synovial hyperplasia, angiogenesis, and inflammation. Notably, TLR8 inhibition effectively alleviates these pathologic processes. In preclinical models, including a CIA mouse model and an RA rabbit model, TLR8 antagonists demonstrated significant therapeutic efficacy, reducing disease severity and ameliorating joint damage. CONCLUSION:TLR8 promotes RA pathogenesis and could serve as a novel therapeutic target for RA.

OBJECTIVE:Although Takayasu arteritis (TAK) is not a prototypical autoantibody-mediated disease, accumulating evidence suggests that B cells are involved. This study aimed to investigate the pathway of B cell activation and its contributions to TAK pathogenesis. METHODS:Histologic analysis of paravascular lymph nodes and affected arteries was conducted to investigate B cell activation pathways in TAK. Bulk RNA-seq, single-cell RNA-seq (scRNA-seq), flow cytometry, and in vitro experiments were performed to characterize the composition, transcriptomic features, and functional profiles of B cells. The numeric and phenotypic alterations induced by tumor necrosis factor (TNF) and JAK inhibition were assessed both in vitro and in four patients with TAK. RESULTS:Histologic (n = 5), flow cytometric (n = 125), and bulk RNA-seq (n = 12) analyses indicated the presence of extrafollicular response and up-regulated age-associated B cell (ABC) production in TAK, along with cross-data set transcriptomic differences between B cells from patients with TAK and systemic lupus erythematosus (SLE). Cross-data set scRNA-seq analysis and in vitro experiments (n = 5) demonstrated that ABC differentiation in TAK was largely uncoupled from antibody-secreting cell (ASC) generation, unlike that in SLE. Functional experiments showed that ABCs exhibited proinflammatory properties, including proinflammatory cytokine production, and that CD11c+ B cells, which contain the ABC compartment, promoted Th17 cell differentiation (n = 6). In vitro, tofacitinib was more effective than adalimumab at reducing ABC proportions and attenuating their proinflammatory phenotype (n = 15), consistent with trends in the exploratory clinical follow-up (n = 4). CONCLUSION:ABCs promote inflammation through proinflammatory functions independent of ASC differentiation in TAK. JAK inhibition exerts distinct suppressive effects on ABCs compared with anti-TNF therapy.

Background:Three key points in managing interstitial lung disease (ILD) in patients with connective tissue disease (CTD) are: First, identifying risk markers or factors for ILD in CTD patients without ILD. Second, diagnosing ILD in CTD patients poses uncertainty about the diagnosis of ILD. Third, predicting treatment response and outcomes of CTD patients with ILD. The current management approaches largely depend on lung biopsy or high-resolution computed tomography (HRCT), both of which have limitations in terms of invasiveness and radiation exposure. Serum biomarkers offer the advantages of non-invasiveness, low cost, radiation-free exposure, and thus represent a potential tool for managing ILD. Methods:Here, we plan to conduct a prospective study to evaluate the value of serum biomarkers for predicting ILD risk, diagnosing ILD, assessing ILD prognosis, and predicting ILD treatment responsiveness in patients with CTD. We named this study "The value of serum biomarkers in diagnosing interstitial lung disease in connective tissue disease: a prospective diagnostic accuracy study" (VELD study). We will prospectively enroll CTD patients with uncertainty regarding ILD who visit the Departments of Rheumatology and Immunology at The Affiliated Hospital of Inner Mongolia Medical University between 2026 and 2028. Their serum specimens will be collected and stored at -80 ℃ for laboratory analyses, including biomarker screening and validation. The predictive and diagnostic values of serum biomarkers for ILD will be estimated using receiver operating characteristic (ROC) curve, decision curve analysis (DCA), logistic regression, net reclassification index (NRI), and integrated discrimination index (IDI). Discussion:The VELD study will provide a novel insight into the clinical role of serum biomarkers in the management of CTD-associated ILD. Trial Registration:chictr.org.cn (ChiCTR2600120197).

Environmental stressors profoundly influence immune function in aquatic organisms, yet the molecular mechanisms linking environmental sensing to immune activation remain poorly understood. Here, we identify transient receptor potential ankyrin 1 (Trpa1) ion channels as critical regulators of interleukin-17a (Il-17a) expression in teleost head kidney cells. Using Nile tilapia (Oreochromis niloticus) as a model, we demonstrate that Trpa1 activation upregulated il-17a (il-17a/f2) more strongly than il-17c or il-17f (il-17a/f3) at the highest concentration tested through calcium-dependent convergence of NF-kappa B- and Nfat1-associated transcriptional pathways. Pharmacological dissection indicated asymmetric pathway contributions: NF-kappa B functioned as an essential convergence node, whereas CaMKII- and calcineurin/Nfat1-related signaling each contributed partially, but neither alone accounted for the full transcriptional response. In vitro, calcium chelation or selective Trpa1 antagonism abolished the AITC-induced il-17a response. Functionally, Trpa1-induced il-17a promoted antimicrobial peptide production, supported il-12 induction, contributed partially to tnf-alpha upregulation, and did not mediate the reduction in il-1 beta. In vivo, cold stress and formaldehyde exposure, but not heat stress, engaged Trpa1/Il-17a-associated responses. Prophylactic Trpa1 agonist treatment significantly improved survival following Aeromonas hydrophila infection, with enhanced bacterial clearance abolished by Il-17a neutralization. These findings support a model in which Trpa1 couples environmental stimuli to Il-17a-associated antimicrobial immunity in teleosts.

ObjectiveObstructive sleep apnea (OSA) is increasingly recognized for its association with significant morbidity and mortality. Despite advances in understanding OSA’s impacts, the role of systemic inflammation in this context remains underexplored. The systemic inflammatory response index (SIRI) has emerged as a potential marker for evaluating inflammatory status and predicting adverse health outcomes. We aim to examine the association between the SIRI and the risks of all-cause and cardiovascular mortality in individuals exhibiting symptoms of obstructive sleep apnea (OSA), with further validation in patients with diagnosed OSA.MethodsA cohort of 9,992 adults with OSA symptoms was derived from the National Health and Nutrition Examination Survey (NHANES) for model development, and an independent external validation cohort of 994 patients with OSA was obtained from the Central Hospital of Wuhan. Multivariate weighted Cox regression, subgroup analyses, restricted cubic spline (RCS) analyses, and receiver operating characteristic (ROC) curves were employed to assess mortality risk in the exploratory cohort, with external validation performed using the Wuhan cohort.ResultsIn the NHANES dataset, elevated SIRI levels were identified as significant independent risk factors for all-cause mortality (adjusted HR = 1.51, 95% CI: 1.16–1.97, p < 0.001) and cardiovascular mortality (adjusted HR = 2.03, 95% CI: 1.17–3.54, p < 0.001) among individuals with OSA symptoms. RCS analysis revealed a non-linear relationship between SIRI and both all-cause and cardiovascular mortality (both p for non-linearity <0.001). Moreover, SIRI demonstrated substantial predictive value for all-cause mortality (AUC = 0.822) and cardiovascular mortality (AUC = 0.806) in this population. These findings were further confirmed in the external validation cohort from the Central Hospital of Wuhan. In this independent dataset, RCS analysis consistently demonstrated a non-linear positive association between SIRI and mortality outcomes, and ROC analysis yielded AUC values of 0.780 for all-cause mortality and 0.866 for cardiovascular mortality, respectively.ConclusionSIRI serves as a significant predictor of mortality in individuals with OSA, highlighting its potential utility in early risk screening for long-term adverse outcomes, both at the population level and clinical settings.

Background Patients with systemic lupus erythematosus (SLE) complicated by immune thrombocytopenia (SLE-ITP) exhibit an increased incidence of bleeding events and significantly reduced long-term survival, with poor responses to conventional therapies as well as biologic agents. Methods In an investigator-initiated, single-arm, dose-escalation trial, six patients with refractory SLE-ITP received anti-CD19 chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy. The primary outcome was safety. Secondary outcomes included overall response rate at time points (complete remission [CR]: platelet count ≥ 100 × 109/L; partial remission [PR]: ≥30 × 109/L with 2-fold baseline increase). Findings All patients achieved clinical response (CR or PR)—with three attaining CR—and discontinued immunosuppressants, with a median follow-up of 12 months. Treatment-related adverse events were limited to grade 1 cytokine release syndrome in two patients, and no immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. Continuously accumulating bone marrow plasma cells, overactivated bone marrow B cell signaling pathways, and weakened activity of the megakaryocyte maturation pathway, along with dysregulated transcription factors, were observed in three PR patients by exploratory single-cell multi-omics. Conclusion These results preliminarily support CD19 CAR T cell therapy as a promising and safe treatment for refractory SLE-ITP. Large-scale trials are needed to verify these conclusions (ClinicalTrials.gov: NCT05930314). Funding This study was supported by the Chinese National Key Technology R&D Program, Ministry of Science and Technology (2021YFC2501300); the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-005); and National High Level Hospital Clinical Research Funding (2025-PUMCH-D-001, 2022-PUMCH-B-013, D-009). This study was also funded and supported by Juventas Cell Therapy Ltd.

ObjectiveTo investigate the clinical efficacy of Yishen Huashi Granules combined with conventional Western medicine in the treatment of stage 2-4 chronic kidney disease （CKD） and its influence on microinflammation.MethodsA total of 88 patients with stage 2-4 chronic kidney disease （CKD） who were treated at Wuhan Fifth Hospital from December 2020 to May 2022 were selected and randomly divided into the control group （44 cases） and observation group （44 cases） according to random number table method. Patients in both groups were given conventional Western medicine treatment， and those in the observation group were additionally given Yishen Huashi Granules. Interventions were performed for 12 weeks. The clinical efficacy， and changes in the blood biochemical indexes total serum protein （TP）， serum Albumin （Alb）， serum creatinine （Scr）， blood urea nitrogen （BUN）， estimated glomerular filtration rate （eGFR）， β2-microglobulin （β2-MG）and microinflammatory indexes ［（white blood cell count （WBC）， lymphocyte count （LYM）， percentage of lymphocytes （LYM%）， neutrophil count （NEUT）， percentage of neutrophils （NEUT%）， neutrophil /lymphocyte ratio （NLR）， hypersensitive C-reactive protein （hs-CRP）， interleukin-6 （IL-6）］ before and after treatment were compared. Meanwhile， patients in both groups were subgrouped into stage G2-3a and stage G3b-4 subgroups based on the eGFR. Changes in renal function indicators （Scr， BUN， eGFR， β2-MG） before and after treatment were compared.ResultsAfter treatment， the total effective rate was significantly higher in the observation group than the control group （81.82% vs. 61.36%， P<0.05）. Post-treatment Hb ［（134.13±20.87） vs （129.62±22.19） g/L］， Alb ［（43.97±4.71） vs （40.63±4.97） g/L］and TP［（73.53±5.93） vs （71.93±7.15） g/L］ were significantly higher than pre-treatment values in the observation group （P<0.05）， and their improvements were superior than the control group （P<0.05）. Renal function indexes were significantly improved after treatment in both groups， and eGFR were significantly higher in the observation group than the control group （P<0.05）. Scr， BUN and β2-MG were significantly lower in the observation group than the control group （P<0.05）. Subgroup analyses showed that renal function indexes were significantly improved after treatment in G2-3a and G3b-4 subgroups （P<0.05）， and their improvements were superior than the control group （P<0.05）. . NEUT， IL-6， WBC， hs-CRP and NLR were significantly reduced， and LYM was significantly elevated after treatment in the observation group （P<0.05）， and their improvements were superior than the control group （P<0.05）. There was no significant difference in the incidence of adverse reactions between the two groups （P>0.05）.ConclusionYishen Huashi Granules combined with traditional Western medicine can effectively improve clinical efficacy， and it is also effective in patients with moderate-to-severe renal insufficiency. The mechanism of action may be related to inhibiting microinflammatory response in vivo， improving nutritional status， protecting renal function and delaying the progression of CKD.

BackgroundSerpinB2 is expressed in airway epithelial cells in nasal polyps and asthma in association with Type-2 inflammation. Allergic rhinitis (AR) is similarly associated with Type-2 inflammation and mucus hypersecretion. MUC5AC has been reported to be regulated by IL-13 in nasal epithelial cells (NECs). This study aimed to evaluate SerpinB2 expression in AR and determine whether SerpinB2 regulates MUC5AC via STAT6 signaling.MethodsSerpinB2 gene expression in single-cell RNA sequencing databases was analyzed through bioinformatics approaches. SerpinB2 and MUC5AC expression levels were evaluated in intermittent or persistent AR patients and healthy controls (HC). Colocalization of SerpinB2 and MUC5AC was assessed by immunofluorescence. Fresh NECs were cultured at air-liquid interface with or without IL-13, SerpinB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SerpinB2, and pSTAT6 inhibitors. SerpinB2, MUC5AC, and STAT6 were analyzed using qRT-PCR, Western blot, immunofluorescence, and ELISA.ResultsSerpinB2 expression was significantly increased in both intermittent and persistent AR compared to normal mucosa from HC. SerpinB2 correlated with MUC5AC expression and colocalized with MUC5AC in NECs from AR patients. In primary NECs in vitro, IL-13 induced both SerpinB2 and MUC5AC expression. Knockdown or overexpression of SerpinB2 correspondingly decreased or increased MUC5AC expression in NECs. STAT6 inhibition similarly reduced SerpinB2-induced MUC5AC expression.ConclusionsSerpinB2 is upregulated in AR NECs and contributes to MUC5AC expression through STAT6 signaling pathway activation. Therefore, targeting SerpinB2 may have therapeutic value in treating AR patients.

OBJECTIVE:Current guidelines recommend postponing surgical intervention in patients with Takayasu's arteritis (TAK) until the disease becomes quiescent, which could exacerbate the incidence of pre-operative adverse events. Considering advances in peri-operative management, the association between pre-operative disease activity and long term prognosis after revascularisation requires re-evaluation. METHODS:This was a multicentre, retrospective cohort study conducted across six tertiary Chinese centres, including patients receiving revascularisation procedures for arterial stenosis or occlusion due to TAK between August 2016 and January 2024. Kaplan-Meier survival analyses, Cox proportional hazards regression, and subgroup analyses were performed to evaluate the relationship between pre-operative disease activity and long term outcomes. Potential prognostic risk factors associated with clinical outcomes were identified using Cox regression analysis and receiver operating characteristic curve analysis. RESULTS:The outcomes of 165 consecutive patients with TAK who underwent 201 surgical interventions, including 94 (46.8%) endovascular revascularisations (EVRs) and 107 (53.2%) open surgical revascularisations (OSRs), were analysed. Interestingly, pre-operative disease activity parameters (active state defined by the 2018 European Alliance of Associations for Rheumatology consensus, Kerr score, and biological inflammation) were of little relevance to the incidence of poor long term outcomes among patients undergoing either EVR or OSR. Moreover, peri-operative immunosuppressive treatment was a prognostic factor for favourable outcomes after EVR (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.20 - 8.75, p = .009), whereas pre-operative thrombin time showed a statistically significant negative correlation with the risk of poor long term outcomes following OSR over the eight year follow up (HR 0.81, 95% CI 0.70 - 0.94, p = .004; p of non-linearity = .42), with an optimal cutoff value of 13 seconds. CONCLUSION:These data indicated a lack of correlation between pre-operative disease activity and long term prognosis. Peri-operative immunosuppressive treatment and thrombin time should be considered in the clinical decision making and peri-operative management of patients undergoing EVR and OSR, respectively.

Takayasu's arteritis (TAK) is a chronic inflammatory disease that often leads to stenosis or occlusion of the common carotid artery (CCA), posing significant risks such as stroke and cognitive impairment. Despite the widespread use of ultrasound in diagnosing and monitoring TAK, the lack of standardized criteria for assessing CCA stenosis has resulted in inconsistent evaluations. This study aims to establish standardized ultrasound diagnostic criteria for CCA stenosis in TAK, focusing on residual inner diameter and wall thickness. A total of 68 TAK patients with 120 CCAs and 120 healthy CCAs controls were included. Ultrasound examinations were performed using the iU22 Philips Healthcare system, with measurements of arterial wall thickness, inner and outer diameters, and carotid blood flow velocity. Head and neck computed tomography angiography (CTA) served as the gold standard for stenosis assessment. Statistical analyses were conducted to evaluate the diagnostic performance of various ultrasound parameters. The study found that the residual inner diameter was the most reliable parameter for assessing CCA stenosis, with high diagnostic accuracy across all stenosis categories (ROC values of 0.901 for ≥ 50

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.

Acute postoperative pain represents a significant clinical challenge, yet its underlying mechanisms remain incompletely understood. A previous study found that PD-1/PD-L1can relieve chronic pain. Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) were quantified in rats at baseline (pre-incision) and at postoperative timepoints of 2, 8, and 24 h. Concurrently, PD-1/PD-L1 expression levels and neuroinflammatory markers were assessed at the 24-hour terminal timepoint. PD-1 inhibitors and agonists were administered via intrathecal injection immediately after surgical incision and at 12 h postoperatively, respectively. It was found that incision surgery resulted in significant postoperative pain accompanied by upregulation of PD-1/PD-L1 and neuroinflammation. Inhibition of PD-1 expression could further exacerbate acute postoperative pain by upregulating neuroinflammation, whereas upregulation of PD-1 expression could alleviate acute postoperative pain by inhibiting neuroinflammation. Activation of the PD-1/PD-L1 pathway relieves acute postoperative pain induced by plantar incision. This may be a therapeutic target for acute postoperative pain.

OBJECTIVES:Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify the high-risk population. METHODS:We included EGPA patients hospitalized in our centre from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac MRI and endomyocardial biopsy results, the patients were divided into three groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS:A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-Control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, P < 0.01), ANCA positivity decreased (41.33/31.82/14.86%, P < 0.01) and lung involvement was reduced (73.33/72.73/43.24%, P = 0.02). In EGPA-EM, cardiac troponin was further elevated (0.27 vs 6.00 ng/ml, P < 0.01), ejection fractions decreased (57.79 vs 33.20%, P < 0.01) while more ST-T abnormality was observed (41.89 vs 20.45%, P = 0.02). The prognosis of EGPA-EM was significantly worse, with a 14.86% death rate and 2-year event-free survival rate below 50%. Furthermore, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [area under the receiver operating characteristic curve 0.85 (95% CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS:We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given in a timely manner and anti-IL-5 antibodies should be be tested in trials.

Our previous work identified several differentially expressed miRNAs (DEmiRNAs) in plasma exosomes from Takayasu’s arteritis (TAK) patients. This study aimed to validate these findings and explore the correlation between DEmiRNAs and clinical parameters in untreated TAK. Plasma exosomes were isolated from 30 untreated TAK patients and 20 healthy controls. qPCR was used to quantify miR-34a-5p, miR-143-3p, miR-22-3p, miR-200c-3p, and miR-21-5p expression. Correlations between miRNA levels, clinical data, inflammation markers, and T helper cell frequencies were analyzed. The target genes of validated DEmiRNAs were identified using mirDIP, and pathway enrichment analysis was performed using GO/KEGG. The effect of validated DEmiRNAs on the MAPK pathway and proliferation in human aortic endothelial cells (HAECs) was investigated in vitro. Only miR-200c-3p expression was validated as significantly downregulated in plasma exosomes from untreated TAK patients. Lower miR-200c-3p levels correlated negatively with ITAS-2010 scores and were associated with relapsed disease. MiR-200c-3p levels also negatively correlated with circulating Th17.1 cell frequencies. In vitro, the TAK exosome treatment activated ERK1/2 and JNK pathways and promoted HAEC proliferation, which was inhibited by the miR-200c-3p mimic. The pathway enrichment analysis showed that the MAPK pathway may be involved. This study confirms the reduced miR-200c-3p expression in plasma exosomes from TAK patients, suggesting its potential as a biomarker for vascular inflammation. MiR-200c-3p may exert protective effects in TAK by suppressing MAPK pathway activation and EC proliferation.

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.