Efficacy of borneol-gypsum in skin regeneration and pain control in toxic epidermal necrolysis: A case report.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions. Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy. However, mortality remains high due to complications like septic shock and multiorgan failures. Innovative approaches for skin care are crucial. This report introduces borneol-gypsum, a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy, might significantly improve skin conditions and patient outcomes in TEN. CASE SUMMARY: A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement. After initial treatment of high-dose corticosteroids and cyclophosphamide, symptom of foot drop improved, absolute eosinophil counts decreased, while limb pain sustained. Duloxetine was added to alleviate her symptom. Subsequently, TEN developed. Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain. This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks. CONCLUSION: Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management, skin regeneration, and patient comfort.

SERPINA3, FGA, AGP1, ITIH3 and SAA1 as novel biomarkers for eosinophilic granulomatosis with polyangiitis diagnosis and activity assessment.

OBJECTIVE: To identify novel biomarkers for diagnosis and prediction of active eosinophilic granulomatosis with polyangiitis (EGPA) through data-independent acquisition (DIA) analysis. METHODS: Plasma from 11 EGPA patients and 10 healthy controls (HCs) were analyzed through DIA to identify potential biomarkers. The results were validated in 32 EGPA patients, 24 disease controls (DCs), and 20 HCs using enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of candidate biomarkers. RESULTS: Thirty-five differentially expressed proteins (DEPs) (24 upregulated and 11 downregulated) were screened between EGPA and HC groups. Five proteins, including serine proteinase inhibitor A3 (SERPINA3), alpha-fibrinogen (FGA), alpha-1 acid glycoprotein 1(AGP1), inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), and serum amyloid A1 (SAA1), were significantly upregulated in EGPA compared with HCs. Apart from SAA1, all proteins were also higher in EGPA patients compared with DCs. Furthermore, a panel of SERPINA3 and SAA1 exhibited potential diagnostic value for EGPA with an area under the curve (AUC) of 0.953, while a panel of SERPINA3, FGA, AGP1, and ITIH3 showed good discriminative power to differentiate EGPA from DCs with AUC of 0.926. Moreover, SERPINA3, FGA, and AGP levels were significantly higher in active EGPA and correlated well with disease activity. A combination of SERPINA3 and AGP1 exhibited an excellent AUC of 0.918 for disease activity assessment. CONCLUSION: SERPINA3, FGA, AGP1, ITIH3 and SAA1 were identified as potential biomarkers for EGPA diagnosis and disease activity assessment. Among them, as a single biomarker, SERPINA3 has the best diagnostic performance.

BACH1 controls hepatic insulin signaling and glucose homeostasis in mice.

Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine phosphatase 1B (PTP1B) and the insulin receptor ß (IR-ß), and loss of BACH1 reduces the interaction between PTP1B and IR-ß upon insulin stimulation and enhances insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of insulin signaling and glucose homeostasis.

A microRNA sponge, LINC02193, promotes neutrophil activation by upregulating ICAM1 and is correlated with ANCA-associated vasculitis.

OBJECTIVE: To investigate the pathogenic role and underlying mechanisms of lncRNAs in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). METHODS：: RNA-sequencing (RNA-seq) was applied to screen the expression profile of lncRNAs in peripheral leukocytes from 5 AAV patients and 5 healthy controls (HC). Candidate lncRNAs were preliminarily verified in peripheral leukocytes from 46 AAV patients and 35 HC by qRT-PCR. Then, the identified LINC02193 was further validated in peripheral neutrophils from 67 AAV patients, 45 HC and 64 disease controls. Correlation between LINC02193 levels and disease activity was analyzed. Then, a loss-of-function study was conducted to investigate the role of LINC02193 in neutrophils activation. Furthermore, bioinformatics analysis, dual luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to explore the mechanism of LINC02193 regulating neutrophils activation. RESULTS: A total of 467 upregulated and 412 downregulated lncRNAs were identified in AAV patients. From top 5 upregulated lncRNAs, an elevation of LINC02193 was validated in a larger sample of AAV patients, and positively correlated with disease activity. Knockdown of LINC02193 inhibited ROS and NO production, NETs release and adhesion to endothelial cells of differentiated human promyelocytic leukaemia HL­60 cells (dHL-60), whereas overexpression of ICAM1 counteracted these effects. Mechanistic analysis demonstrated that LINC02193 acted as a miR-485-5p sponge to relieve the repressive effect of miR-485-5p on ICAM1, thus promoting ICAM1 expression. CONCLUSION: LINC02193, a novel lncRNA identified in AAV could function as competing endogenous RNAs (ceRNA) for miR-485-5p to promote ICAM1 expression and neutrophils activation, suggesting its potential as a therapeutic target of AAV.

BACH1 regulates the differentiation of vascular smooth muscle cells from human embryonic stem cells via CARM1-mediated methylation of H3R17.

The role of BACH1 in the process of vascular smooth muscle cell (VSMC) differentiation from human embryonic stem cells (hESCs) remains unknown. Here, we find that the loss of BACH1 in hESCs attenuates the expression of VSMC marker genes, whereas overexpression of BACH1 after mesoderm induction increases the expression of VSMC markers during in vitro hESC-VSMC differentiation. Mechanistically, BACH1 binds directly to coactivator-associated arginine methyltransferase 1 (CARM1) during in vitro hESC-VSMC differentiation, and this interaction is mediated by the BACH1 bZIP domain. BACH1 recruits CARM1 to VSMC marker gene promoters and promotes VSMC marker expression by increasing H3R17me2 modification, thus facilitating in vitro VSMC differentiation from hESCs after the mesoderm induction. The increased expression of VSMC marker genes by BACH1 overexpression is partially abolished by inhibition of CARM1 or the H3R17me2 inhibitor TBBD in hESC-derived cells. These findings highlight the critical role of BACH1 in hESC differentiation into VSMCs by CARM1-mediated methylation of H3R17.

The role of plateletcrit in Takayasu arteritis: A potential biomarker for disease activity and 6-month treatment response.

OBJECTIVES: To determine the role of plateletcrit as a potential biomarker for disease activity and treatment response in Takayasu arteritis (TAK). METHODS: Totally, 215 newly diagnosed TAK patients were consecutively enrolled. Demographic data, clinical manifestations, laboratory and imaging examinations, and treatment strategy were recorded at baseline and at each visit during the 6-month treatment period. Normal plateletcrit (0.1%-0.4%) and hyper-plateletcrit (>0.4%) observed at baseline were used as group criteria. RESULTS: At baseline, the overall plateletcrit was 0.32 (0.24-0.38)%, with a normal and high level observed in 172 (80.00%) and 43 (20.00%) patients, respectively. Baseline plateletcrit was significantly higher in patients with active disease and associated with inflammatory biomarkers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin (IL)-6 (all p < .01). At 6 months, complete remission was achieved in 171 (79.53%) patients, and a significant decrease in plateletcrit was observed in these cases (p < .01). Patients with a normal baseline plateletcrit were more likely to achieve complete remission compared to those with a high baseline plateletcrit (HR = 4.65, 95% CI: 2.38-19.08, p < .01). In addition, ESR (p = .01) and IL-6 (p = .02) levels were still higher in patients with a high baseline plateletcrit at 6 months. Progression of vascular lesions was indicated in 18 (8.37%) patients at 6 months, and these patients also had significantly higher baseline plateletcrit (p = .03). CONCLUSION: Plateletcrit levels were positively related to disease activity and inflammatory index in TAK. Importantly, patients with high baseline plateletcrit levels may show a worse treatment response at 6 months.

Exploration of molecular signatures associated with different clinical features of Takayasu arteritis based on a prospective cohort study.

Takayasu arteritis (TAK) is complicated disorder without reliable biomarkers. Here, we aimed to explore TAK-associated factor panels and their changes after biologic treatment. Five factor panels were identified: 1. systemic inflammation: C3, ESR, CRP, PLT, IL-6, C4, and IgG; 2. vascular inflammation: YKL40, IL-16, PTX3, and CCL2; 3. immune regulation panel: IL-10, IFN-γ, CCL5, and MMP1; 4. angiogenesis and fibrosis: FGF, PDGFAB, and VEGF; and 5. vascular remodeling: CD19+ B cell ratio, MMP3, and leptin. Panel 1 parameters were closely related to disease activity, while Panel 5 parameters, particularly CD19+ B cell ratio and leptin, were significantly higher in ischemic patients. After treatment, tocilizumab had a stronger inhibitory effect on Panel 1 parameters, PTX3, and YKL-40, while adalimumab led to an increase in IL-16, CCL2, and leptin levels. Altogether, these data expanded our knowledge regarding molecular background in TAK development and shed light on precise treatment in future studies.

Single-Cell RNA-Sequencing Reveals Peripheral T Helper Cells Promoting the Development of IgG4-Related Disease by Enhancing B Cell Activation and Differentiation.

Abnormal B cell differentiation plays a critical role in IgG4-related disease (IgG4-RD), but the underlying mechanism remains largely unknown. We investigated the cell landscape from three IgG4-RD retroperitoneal tissues and three control tissues using single-cell RNA-sequencing. Critical cell type or markers were further validated in the peripheral blood from the patients with IgG4-RD and healthy controls via flow cytometry as well as in the IgG4-RD and control tissue via immunofluorescence staining. The increases in B cells, plasma cells, and CD4+ T cells were found in IgG4-RD retroperitoneal tissue. Importantly, among CD4+ T cells, an increase in CD4+CXCR5-PD1hi peripheral T helper (Tph) cells with a high expression of IL-21 and TIGIT was discovered in IgG4-RD tissue, which was further validated in peripheral blood of the patients with IgG4-RD. The Tph cell and TIGIT+ Tph cell proportion were remarkably higher in active IgG4-RD patients and correlated with disease activity. Moreover, TIGIT+CD4+ cells were able to promote B cell differentiation via IL-21. Our study revealed that Tph cells are increased in IgG4-RD and probably play critical roles in B cell differentiation through TIGIT-IL-21 axis. Peripheral Tph cell and TIGIT+Tph cell are potential markers for IgG4-RD disease activity.

Treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis: an open-label study.

OBJECTIVE: This study aimed to compare the efficacy and safety of adalimumab (ADA) versus tocilizumab (TCZ) in patients with Takayasu arteritis (TAK). METHODS: This was a randomized, controlled, open-label study. Forty patients with active and severe TAK were enrolled. They were treated with ADA (n = 21) combined with glucocorticoids (GCs) and methotrexate (MTX) or TCZ (n = 19) combined with GCs and MTX. The planned follow-up duration was 12 months. The primary end point was the efficacy rate (ER) at 6 months. The secondary endpoints included ER at 9 and 12 months, relapse rate, GC tapering, adverse effects, and life quality changes during treatment. RESULTS: In the intention-to-treat (ITT) population, the ER at 6 months was higher in the ADA group (85.71% vs 52.63%, P= 0.02). A similar direction of effect was noted in the per-protocol set (89.47% vs 62.50%, P= 0.06). The percentages of patients who achieved a GC dose of ≤ 10 mg/day at 6 months were similar between the ADA and TCZ groups (47.37% vs 43.75%, P= 0.83). The ERs at 9 and 12 months were similar between the two groups (P> 0.05). During the first 12 months of treatment, the relapse rate and adverse event incidence were comparable between the two groups (ADA vs TCZ: 9.52% vs 10.53%, P= 0.96; 38.10% vs 47.37%, P= 0.55, respectively). CONCLUSION: ADA combined with GCs and MTX may be more efficacious than TCZ combined with GCs and MTX among patients with active and severe TAK. TRIAL REGISTRATION: Clinicaltrials.gov; NCT04300686.

Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway.

AIMS: BACH1 is up-regulated in hypertrophic hearts, but its function in cardiac hypertrophy remains largely unknown. This research investigates the function and mechanisms of BACH1 in the regulation of cardiac hypertrophy. METHODS AND RESULTS: Male cardiac-specific BACH1 knockout mice or cardiac-specific BACH1 transgenic (BACH1-Tg) mice and their respective wild-type littermates developed cardiac hypertrophy induced by angiotensin II (Ang II) or transverse aortic constriction (TAC). Cardiac-specific BACH1 knockout in mice protected the hearts against Ang II- and TAC-induced cardiac hypertrophy and fibrosis, and preserved cardiac function. Conversely, cardiac-specific BACH1 overexpression markedly exaggerated cardiac hypertrophy and fibrosis and reduced cardiac function in mice with Ang II- and TAC-induced hypertrophy. Mechanistically, BACH1 silencing attenuated Ang II- and norepinephrine-stimulated calcium/calmodulin-dependent protein kinase II (CaMKII) signalling, the expression of hypertrophic genes, and hypertrophic growth of cardiomyocytes. Ang II stimulation promoted the nuclear localization of BACH1, facilitated the recruitment of BACH1 to the Ang II type 1 receptor (AT1R) gene promoter, and then increased the expression of AT1R. Inhibition of BACH1 attenuated Ang II-stimulated AT1R expression, cytosolic Ca2+ levels, and CaMKII activation in cardiomyocytes, whereas overexpression of BACH1 led to the opposite effects. The increased expression of hypertrophic genes induced by BACH1 overexpression upon Ang II stimulation was suppressed by CaMKII inhibitor KN93. The AT1R antagonist, losartan, significantly attenuated BACH1-mediated CaMKII activation and cardiomyocyte hypertrophy under Ang II stimulation in vitro. Similarly, Ang II-induced myocardial pathological hypertrophy, cardiac fibrosis, and dysfunction in BACH1-Tg mice were blunted by treatment with losartan. CONCLUSION: This study elucidates a novel important role of BACH1 in pathological cardiac hypertrophy by regulating the AT1R expression and the Ca2+/CaMKII pathway, and highlights potential therapeutic target in pathological cardiac hypertrophy.

Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using Whole-Exome Sequencing.

OBJECTIVE: Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole-exome sequencing (WES). METHODS: This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti-citrullinated protein antibody (ACPA-) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole-exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA- PR and ACPA+ PR. RESULTS: Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA-. We identified 8 novel loci (in the ACPA- PR group: ZNF503, RPS6KL1, HOMER3, HLA-DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA- PR group: HLA-DRB1*0803 and HLA-DQB1; in the ACPA+ PR group: HLA-DPA1*0401) that were associated with PR and that surpassed genome-wide significance (P < 5 × 10-8 ). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R2 < 0.025), whereas ACPA+ PR and ACPA- PR showed a moderate genetic correlation (0.38 < R2 < 0.8). CONCLUSION: This study demonstrated the distinct genetic background between ACPA- and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar.

BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility.

The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.

Comparison of the efficacy and safety of leflunomide versus placebo combined with basic prednisone therapy in patients with active disease phase of Takayasu arteritis: study protocol for a randomized, double-blinded controlled trial (Takayasu arteritis clinical trial in China: TACTIC).

Background: Takayasu arteritis (TAK) is an immune-induced granulomatous vasculitis that occurs primarily in young Asian women. Our previous cohort studies have indicated that leflunomide (LEF), which can lead to rapid induction and might be a promising alternative treatment for TAK. Objectives: To compare the efficacy and safety of LEF versus placebo combined with prednisone for active TAK in a Chinese population. Design: This will be a multicenter, randomized, double-blinded controlled trial aiming to recruit 116 TAK patients with active disease. This study will last 52 weeks. Methods and analysis: Participants will be assigned randomly to the LEF intervention arm or placebo control arm at a 1:1 ratio. Initially, LEF combined with prednisone will be given to the intervention arm and a placebo tablet combined with prednisone will be given to the placebo arm. At the end of week 24, subjects who achieved clinical remission or partial clinical remission will proceed to maintenance therapy with LEF to the end of week 52; those who did not achieve clinical remission or partial clinical remission in the LEF intervention arm will drop out from the study, and those in the placebo control arm will switch to LEF treatment to week 52. The primary endpoint will be the clinical remission rate of LEF versus placebo at the end of week 24. The secondary endpoints will be the time to clinical remission, mean dose of prednisone, disease recurrence, time to recurrence, adverse events, as well as clinical remission in subjects who switched from the placebo control arm to LEF therapy after week 24. Intention to treat will be the primary analysis. Discussion: This is the first randomized double-blinded placebo-controlled trial to clarify the efficacy and safety of LEF in treating active TAK. The results will provide more evidence for TAK management. Registration: ClinicalTrials.gov identifier: NCT02981979.

Identification of key candidate genes and pathways in rheumatoid arthritis and osteoarthritis by integrated bioinformatical analysis.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common joint disorders. Although they have shown analogous clinical manifestations, the pathogenesis of RA and OA are different. In this study, we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE153015 to identify gene signatures between RA and OA joints. The relevant data on 8 subjects obtained from large joints of RA patients (RA-LJ), 8 subjects obtained from small joints of RA patients (RA-SJ), and 4 subjects with OA were investigated. Differentially expressed genes (DEGs) were screened. Functional enrichment analysis of DEGs including the Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, which were mainly associated with T cell activation or chemokine activity. Besides, protein-protein interaction (PPI) network analysis was performed, and key modules were identified. Hub genes of RA-LJ and OA groups were screened, they were CD8A, GZMB, CCL5, CD2, and CXCL9, whereas CD8A, CD2, IL7R, CD27, and GZMB were hub genes of RA-SJ and OA group. The novel DEGs and functional pathways between RA and OA identified in this study may provide new insight into the underlying molecular mechanisms and therapeutic strategies of RA and OA.

COVID-19 vaccine uptake, hesitancy and clinical effects on patients with Takayasu's arteritis: A web-based questionnaire survey from a large cohort.

Objective: This study aimed to investigate the Coronavirus disease 2019 (COVID-19) vaccination rate, reasons for vaccine hesitancy and clinical effects on patients with Takayasu's arteritis (TAK). Methods: A web-based survey was administered to a TAK cohort established by the Department of Rheumatology, Zhongshan Hospital through WeChat in April, 2022. Responses from a total of 302 patients were received. The Sinovac or Sinopharm inactivated vaccination rate, side effects, and vaccine hesitancy reasons were analyzed. In addition, disease flare, new disease onset, and changes of immune-related parameters after vaccination were analyzed in vaccinated patients. Results: Among 302 patients, 93 (30.79%) received the inactivated COVID-19 vaccination. Among the 209 unvaccinated patients, the most common reason for hesitancy were concern about side effects (136, 65.07%). Vaccinated patients had a longer disease duration (p = 0.08) and lower use of biologic agents (p < 0.001); 16 (17.20%) of the 93 vaccinated patients developed side effects, and most of them were mild; 8 (8.60%) developed disease flares or new-onset disease 12-128 days post-vaccination and 2 (2.15%) developed serious adverse effects (vision defect and cranial infarction). Immune-related parameters of 17 patients indicated decreases in IgA and IgM after vaccination (p < 0.05). Eighteen (19.35%) of the 93 vaccinated patients were diagnosed post-vaccination.These patients had a significantly higher percentage of CD19+ B cells at disease onset (p < 0.05) than the unvaccinated patients diagnosed at the same time. Conclusion: The vaccination rate was low in TAK, which was mainly caused by concerns about negative effects of vaccination on their disease. An acceptable safety profile was observed in vaccinated patients. The risk of disease flare associated with COVID-19 vaccination warrants further investigation.

Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION: Chictr.org, ChiCTR2000039799.

PET vascular activity score for predicting new angiographic lesions in patients with Takayasu arteritis: a Chinese cohort study.

OBJECTIVE: To investigate the ability of 18F-fluorodeoxyglucose PET/CT to predict new lesions in Takayasu arteritis. METHODS: Eighty-two Chinese patients with newly diagnosed Takayasu arteritis were recruited. Their clinical characteristics, serum biomarkers and imaging results were recorded at baseline and every visit. They were followed up for at least 2 years. New angiographic lesions were evaluated by magnetic resonance angiography. Baseline PET vascular activity scores (PETVAS) for predicting new lesions were evaluated. RESULTS: At baseline, a moderate correlation was observed between PETVAS and ESR (r = 0.74, P < 0.01) and CRP level (r = 0.69, P < 0.01). Overall, 18 (22%) patients showed new lesions on imaging during a median follow-up time of 36 months. The median time to the first occurrence of new lesions was 18 months. Compared with patients without new lesions, the patients with new lesions included more female patients (67.2% vs 94.4%, P = 0.03), patients with higher ESR values (20 vs 49, P = 0.02) and patients with active disease (62.5% vs 94.4%, P < 0.01). Multivariate Cox regression analysis revealed PETVAS was an independent risk factor for new angiographic lesions (PETVAS ≥8, hazard ratio = 7.56; 95% CI 2.20, 26.01, P < 0.01) with adjustment of age, sex, chest pain, ESR and Physician Global Assessment. Furthermore, patients with PETVAS ≥8 at baseline were more likely to experience adverse events including arterial ischaemic events during the follow-up. CONCLUSION: PETVAS showed good performance in predicting new lesions in Takayasu arteritis.

Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing.

OBJECTIVES: The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap. METHODS: Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis. RESULTS: Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to CTLA4 and CPLX1, emerged as novel genetic risk loci in vasculitis. Most of these polymorphisms appeared to affect vasculitis by regulating gene expression. In this regard, for some of these common signals, potential causal genes were prioritised based on functional annotation, including CTLA4, RNF145, IL12B, IL5, IRF1, IFNGR1, PTK2B, TRIM35, EGR2 and ETS2, each of which has key roles in inflammation. In addition, drug repositioning analysis showed that several drugs, including abatacept and ustekinumab, could be potentially repurposed in the management of the analysed vasculitides. CONCLUSIONS: We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis.

Associations of microcirculation damage on nailfold capillaroscopy with supra-aortic severe ischemic events in patients with Takayasu arteritis.

OBJECTIVE: To evaluate the clinical characteristics and nailfold microcirculation and explore the associations with severe ischemic events (SIEs) in Takayasu arteritis (TA) with supra-aortic involvement. METHODS: Eighty-one patients with supra-aortic artery involvement who underwent nailfold video-capillaroscopy (NVC) of their hands were enrolled from the East China TA (ECTA) cohort between August and December 2021. Clinical features and capillaroscopy variables associated with supra-aortic SIEs were analyzed by multivariate logistic regression. RESULTS: Overall, 71 patients were female, and 42 experienced supra-aortic SIEs, among whom there was a higher prevalence of hypertension and the number of supra-aortic artery stenosis (P = 0.005, and 0.003, respectively). Furthermore, intergroup differences in capillary density (P < 0.001) and minor morphology abnormalities (P < 0.001) were significant. After adjustment for all confounders, multivariate logistic regression revealed hypertension (odds ratio [OR]: 7.3, 95% confidence interval [CI]: 1.6-33.7, P = 0.011), the number of supra-aortic arteries stenosis (≥4, OR: 6.8, 95% CI: 1.4-34.6, P = 0.020), capillary density (≤7.2/mm, OR: 43.0, 95% CI: 7.0-264.6, P < 0.001) and minor abnormalities (OR: 34.2, 95% CI: 3.6-325.1; P = 0.002) were independent risk factors for supra-aortic SIEs. capillary density (≤7.2/mm) and minor abnormalities or combined with at least two of the three items in the matrix model showed the probability of supra-aortic SIEs was 61.2-87.6%. CONCLUSION: Decreased capillary density and morphologic abnormalities indicated that hypoperfusion was more likely to be observed in supra-aortic SIEs patients. Combined NVC indicators could be instrumental for early identification of supra-aortic SIEs. Key Points • Minor morphological abnormalities and hemorrhages were only observed in supra-aortic SIEs patients. • Capillaroscopic density and minor morphological abnormalities or combined with at least two of the three items in the matrix model showed the probability occurrence of supra-aortic SIEs was 61.2-87.6%.