Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet's disease.

Behçet's disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors. We observed prominent expansion and transcriptional changes in monocytes in PBMCs from BD patients. Deciphering the monocyte heterogeneity revealed the accumulation of C1q-high (C1qhi) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1qhi monocyte-ended trajectory. Further experiments showed that C1qhi monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1qhi monocytes were induced by activated interferon-γ (IFN-γ) signaling in BD patients and were decreased by tofacitinib treatment. Our study illustrates the BD immune landscape and the unrecognized contribution of C1qhi monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.

Shelterin dysfunction promotes CD4+ T cell senescence in Behçet's disease.

OBJECTIVES: To investigate the potential role of shelterin dysfunction in naïve CD4+ T cells in the pathogenesis of Behçet's disease (BD). METHODS: Naïve CD4+ T cells were isolated from 40 BD patients and 40 sex- and age-matched healthy controls (HC). Senescent profiles, shelterin subunits expression, telomere length, telomerase activity and critical DNA damage response (DDR) were evaluated. Telomere repeat factor-2 (TRF2) silencing was conducted for further validation. RESULTS: Compared with HC, BD patients had significantly decreased naïve CD4+ T cells, increased cell apoptosis, senescence, and productions of TNF-α and IFN-γ upon activation. Notably, BD naïve CD4+ T cells had shortened telomere, impaired telomerase activity, and expressed lower levels of shelterin subunits TRF2, TRF1- and TRF2-Interacting Nuclear Protein 2 (TIN2) and Repressor/Activator Protein 1 (RAP1). Furthermore, BD naïve CD4+ T cells exhibited significantly increased DDR, evidenced by elevated phosphorylated ataxia telangiectasia (AT) mutated (pATM), phosphorylated p53 (pp53) and p21. Finally, TRF2 silencing markedly upregulated DDR, apoptosis and proinflammatory cytokines production in HC naïve CD4+ T cells. CONCLUSION: Our study demonstrated that TRF2 deficiency in BD naïve CD4+ T cells promoted cell apoptosis and senescence, leading to proinflammatory cytokines overproduction. Therefore, restoring TRF2 might be a promising therapeutic strategy for BD.

Infliximab for parenchymal neuro-Behçet's syndrome: case series and meta-analysis.

OBJECTIVES: This study aims to evaluate the efficacy and safety of infliximab (IFX) in patients with parenchymal neuro-Behçet's syndrome (p-NBS). METHODS: We retrospectively analysed eleven p-NBS patients treated with IFX at our institution and combined them with studies from database searches for a meta-analysis. Pooled estimates of clinical response (complete and partial remission) and MRI improvement at months 3, 6, and 12 were calculated. RESULTS: One patient achieved CR and the other ten patients achieved PR at our institution. 8 studies (77 patients) were included in the meta-analysis. At 3, 6, and 12 months, 97% (95%CI 61.9-100%), 89.6% (95%CI 45.9-100%), 100% (95%CI 96.0-100%) of patients showed clinical response and 100% (95%CI 89.7-100%), 89.1% (95% CI 26.3-100%), 99.5% (95% CI 96.0-100%) of patients showed radiological improvement, respectively. Severe adverse events were observed in 7 patients. CONCLUSIONS: IFX was effective and relatively safe for p-NBS. Patients should be re-evaluated after 3 months of IFX to determine further therapy.

Caffeine and neonatal acute kidney injury.

Acute kidney injury is one of the most threatening diseases in neonates, with complex pathogenesis and limited treatment options. Caffeine is a commonly used central nervous system stimulant for treating apnea in preterm infants. There is compelling evidence that caffeine may have potential benefits for preventing neonatal acute kidney injury, but comprehensive reports are lacking in this area. Hence, this review aims to provide a summary of clinical data on the potential benefits of caffeine in improving neonatal acute kidney injury. Additionally, it delves into the molecular mechanisms underlying caffeine's effects on acute kidney injury, with a focus on various aspects such as oxidative stress, adenosine receptors, mitochondrial dysfunction, endoplasmic reticulum stress, inflammasome, autophagy, p53, and gut microbiota. The ultimate goal of this review is to provide information for healthcare professionals regarding the link between caffeine and neonatal acute kidney injury and to identify gaps in our current understanding.

Baricitinib for the treatment of intestinal Behçet's disease: A pilot study.

OBJECTIVES: The pilot study aims to explore the efficacy and safety of baricitinib in treating refractory intestinal Behçet's disease (BD). METHODS: We consecutively enrolled patients with refractory intestinal BD from October 2020 to September 2022. They were treated with baricitinib 2-4 mg daily, with background glucocorticoids and immunosuppressants. Efficacy assessment included the global gastrointestinal symptom scores, the endoscopy scores, the Disease activity index for intestinal Behçet's disease (DAIBD), and the inflammatory parameters. Side effects were recorded. RESULTS: The thirteen patients (six males and seven females) had a median follow-up of eleven months, 76.92% (10/13) patients achieved complete remission of global gastrointestinal symptom scores, and 66.7% (6/9) had mucosal healing on endoscopy. The DAIBD scores decreased significantly, as well as the C-reactive protein level. Baricitinib showed a glucocorticoid-sparing effect, and the safety profile is favorable. CONCLUSION: Baricitinib might be a potential choice in treating refractory intestinal BD.

Baricitinib for the treatment of refractory vascular Behçet's disease.

OBJECTIVE: The pilot study aims to evaluate the effectiveness and safety of baricitinib in Behcet's Disease (BD) patients with refractory vascular involvement. METHODS: We consecutively enrolled vascular/cardiac BD patients who received baricitinib (2 mg/day) along with glucocorticoids (GCs) and immunosuppressants in our center. Efficacy assessment mainly depends on the proportion of clinical remission and side effects were recorded. RESULTS: 17 patients (12 males) were included with a mean follow-up of 10.7 ± 5.3 months. At 3 months of follow-up, 76.5% of patients achieved a complete response and the proportion increased to 88.2% at the last visit. During follow-up, ESR (p < 0.01) and hsCRP (p < 0.0001) decreased significantly, as well as Behçet's Disease Current Activity Form score (p < 0.01). In addition, baricitinib showed a GCs-sparing effect. No serious adverse events were noted. CONCLUSIONS: Our study suggests that baricitinib is well-tolerated and effective in treating refractory vascular/cardiac BD patients.

Comparison of Treatment and Prognosis Between Follicular Variant Papillary Thyroid Carcinoma and Classical Papillary Thyroid Carcinoma.

This cohort study evaluated the associations of different treatments with the prognosis of follicular variant papillary thyroid carcinoma (FVPTC) and classical papillary thyroid carcinoma (CPTC) patients. The data of 69034 PTC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year mortality of CPTC and FVPTC patients receiving surgery, radiation and combination therapy were compared. The univariable and multivariable cox proportional risk models explored the associations between different treatments and the 5-year mortality in CPTC and FVPTC patients. The 5-year mortality of CPTC patients was 2.81% and FVPTC patients was 2.47%. Compared with CPTC receiving lobectomy and/or isthmectomy, those not receiving surgery were associated with increased risk of 5-year mortality [Hazards ratio (HR)=3.27, 95% confidence interval (CI): 2.55-4.20] while total thyroidectomy was correlated with reduced risk of 5-year mortality (HR=0.67, 95%CI: 0.55-0.80). Radioactive iodine (RAI) was linked with decreased risk of 5-year mortality in CPTC patients (HR=0.57, 95%CI: 0.50-0.65). CPTC patients undergoing both surgery and radiation were related to decreased risk of 5-year mortality compared with those receiving surgery only (HR=0.55, 95%CI: 0.48-0.63). CPTC patients receiving neither surgery nor radiation (HR=4.53, 95%CI: 3.72-5.51) or those receiving radiation (HR=1.98, 95%CI: 1.13-3.48) were correlated with elevated risk of 5-year mortality. The elevated risk of 5-year mortality in FVPTC patients was reduced in those undergoing RAI (HR=0.63, 95%CI: 0.51-0.76). In conclusion, combination therapy was associated with decreased risk of 5-year mortality in CPTC and FVPTC patients, which might provide a reference for the management of these patients.

Ferroptosis-associated lncRNA prognostic signature predicts prognosis and immune response in laryngeal squamous carcinoma.

In order to construct a prognostic model of ferroptosis-related lncRNA associated with laryngeal carcinoma and to investigate its prognostic value, RNA sequencing, genomic mutation, and clinical data of laryngeal squamous carcinoma patients were collected from the TCGA database. Patients were randomly divided into train and test groups. Cox regression analysis and lasso regression analysis were performed on the data of patients in the training group, and their independent prognostic effect was validated in the test group and the whole cohort. Data from 123 laryngeal squamous carcinoma patients in the TCGA database were collected. According to previous literature, 484 ferroptosis-related genes were collected, and 912 ferroptosis-related lncRNAs were obtained by co-expression. Cox models suggested six lncRNAs involved in ferroptosis (AC083862.2, CYTOR, AC114296.1, LINC02768, GATA2-AS1, CTB-178M22.2). Patients were divided into high-risk and low-risk groups based on median risk scores. Kapkan-Meier survival curve results showed a statistical difference in survival between the high- and low-risk groups. Receiver operating characteristic curves and principal component analysis demonstrated the high accuracy of the model. Univariate and multifactorial Cox regression analyses and column plots demonstrated risk scores as independent prognostic factors. The distribution of prognostic marker risk scores was correlated with clinical staging. Immune infiltration studies suggested the model was associated with immune checkpoints and multiple immune functions. GATA2-AS1 was able to promote cell proliferation, cell migration, and cell invasion. This study identified six lncRNAs associated with ferroptosis in laryngeal squamous carcinoma as prognostic predictors, which may be promising biomarkers involved in the treatment of laryngeal squamous carcinoma.

Gut microbiota and neonatal acute kidney injury biomarkers.

One of the most frequent issues in newborns is acute kidney injury (AKI), which can lengthen their hospital stay or potentially raise their chance of dying. The gut-kidney axis establishes a bidirectional interplay between gut microbiota and kidney illness, particularly AKI, and demonstrates the importance of gut microbiota to host health. Since the ability to predict neonatal AKI using blood creatinine and urine output as evaluation parameters is somewhat constrained, a number of interesting biomarkers have been developed. There are few in-depth studies on the relationships between these neonatal AKI indicators and gut microbiota. In order to gain fresh insights into the gut-kidney axis of neonatal AKI, this review is based on the gut-kidney axis and describes relationships between gut microbiota and neonatal AKI biomarkers.

Effect of COVID-19 on non-performing loans in China.

We examine the resilience of Chinese banks during the COVID-19 pandemic by investigating non-performing loan (NPL) ratios. We find that despite the reduction in the growth rate of total bank lending, bank NPL ratios significantly increase during the COVID-19 crisis. Banks with high-quality capital are more effective in controlling their NPL ratios during the Crisis. Big Five banks, state-owned banks and domestic banks have lower NPL ratios than their counterparts during the Crisis.

Transcriptional analysis of neutrophils from patients with Behçet's disease reveals activation and chemotaxis of neutrophils.

Behçet's disease (BD) is a systemic vasculitis characterized by neutrophil activation with unclear pathogenesis. This study aimed to explore the transcriptional profiles of BD neutrophils and identify specific gene signatures. We performed RNA sequencing on neutrophils from treatment-naive active BD patients and healthy controls, then analyzed differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) and transcription regulatory network. Quantitative real-time PCR and Western Blot were used to validate chemotaxis-related DEGs expression. We detected 567 DEGs, including 520 upregulated genes and 47 downregulated genes. 9 KEGG pathways were enriched, dominated by the NF-κB pathway and chemotaxis. The transcription regulatory network suggests ETS1 regulated the enhanced chemotaxis of BD neutrophils. Validation experiments demonstrated the overexpression of ETS1, CCR6 and CCL5 in BD neutrophils compared with HC, and ETS1 was significantly increased in vascular BD compared with other BD subgroups. Our study revealed increased activation and chemotaxis of BD neutrophils characterized by the overexpression of CCL5, CCR6 and ETS1.

Methylprednisolone pulse therapy promotes the differentiation of regulatory T cells by inducing the apoptosis of CD4+ T cells in patients with systemic lupus erythematosus.

OBJECTIVES: To investigate the differentiation of regulatory T cells (Tregs) induced by methylprednisolone (MP) pulse therapy in patients with Systemic Lupus Erythematosus (SLE). METHODS: We enrolled 30 patients with SLE and analyzed peripheral blood mononuclear cells (PBMCs) before and after MP pulse therapy. Peripheral Tregs, apoptosis of PBMCs subsets, and TGFß production by monocytes was quantified by flow cytometry. Proliferation and IFN-γ production of CD4+ T cells were measured. Furthermore, TGFß1 production by human monocyte-derived macrophages (HMDM) stimulated with MP-treated CD4+ T cells were quantified by ELISA. RESULTS: Peripheral Tregs was significantly increased after MP pulse therapy (6.76 ± 1.46% vs. 3.82 ± 1.02%, p < 0.01), with an expansion of Nrp1- induced Tregs (4.54 ± 0.46% vs. 1.75 ± 0.38%, p < 0.01). Proliferation and IFN-γ production of CD4+ T cells were significantly decreased after MP pulse therapy. MP pulse therapy induced CD4+ T cell apoptosis (early apoptosis, 26.34 ± 3.54% vs. 14.81 ± 2.89%, p < 0.01) and TGFß expression on monocytes (6.02% vs. 2.45%, p < 0.01). Furthermore, MP induced CD4+ T cell apoptosis in vitro, which stimulated HMDM to produce TGFß. Moreover, elevated TGFß level in supernatant from HMDM stimulated with MP-treated CD4+ T cells promoted Tregs differentiation. CONCLUSIONS: MP pulse therapy induces CD4+ T cell apoptosis, which promotes monocytes to produce TGFß and further facilitates Tregs differentiation. Newly-differentiated Tregs suppress proliferation and IFN-γ production of CD4+ T cells and contribute to immunoregulatory milieu after MP pulse therapy.

Parkinson's disease patients with freezing of gait have more severe voice impairment than non-freezers during "ON state".

BACKGROUND: Speech disorders and freezing of gait (FOG) in Parkinson's disease (PD) may have some common pathological mechanisms. The purpose of this study was to compare the acoustic parameters of PD patients with dopamine-responsive FOG (PD-FOG) and without FOG (PD-nFOG) during "ON state" and explore the ability of "ON state" voice features in distinguishing PD-FOG from PD-nFOG. METHODS: A total of 120 subjects, including 40 PD patients with dopamine-responsive FOG, 40 PD-nFOG, and 40 healthy controls (HCs) were recruited. All subjects underwent neuropsychological tests. Speech samples were recorded through the sustained vowel pronunciation tasks during the "ON state" and then analyzed by the Praat software. A set of 27 voice features was extracted from each sample for comparison. Support vector machine (SVM) was used to build mathematical models to classify PD-FOG and PD-nFOG. RESULTS: Compared with PD-nFOG, the jitter, the standard deviation of fundamental frequency (F0SD), the standard deviation of pulse period (pulse period SD) and the noise-homophonic-ratio (NHR) were increased, and the maximum phonation time (MPT) was decreased in PD-FOG. The above voice features were correlated with the freezing of gait questionnaire (FOGQ). The average accuracy, specificity, and sensitivity of SVM models based on 27 voice features for classifying PD-FOG and PD-nFOG were 73.57%, 75.71%, and 71.43%, respectively. CONCLUSIONS: PD-FOG have more severe voice impairment than PD-nFOG during "ON state".

The clinical features, image findings and risk factors of vena cava syndrome in Behçet's syndrome.

OBJECTIVES: To investigate the clinical features, image findings, and potential risk factors of vena cava syndrome (VCS) in Behçet's syndrome (BS). METHODS: We conducted a case-control study in our BS registry database from 2012 to 2021. Fifty-five BS patients with VCS were enrolled in the case group, and two BS patients without VCS were selected as controls for each VCS case using risk-set-sampling. Multivariable logistic regression was used to detect the risk factors of VCS, and the outcome of these patients was also analysed. We also conducted an exploratory study to evaluate spectral computed tomography (CT) imaging in detecting thrombosis in BS patients with inferior VCS (IVCS). RESULTS: Multivariable logistic regression analysis revealed male gender (OR 11.16, 95%CI 3.34-37.32), early-onset BS (<18 years) (OR 5.57, 95%CI 1.58-19.69), ESR >60 mm/hr (OR 3.83, 95%CI 1.02-12.23) and pathergy reaction (OR 5.10, 95%CI 2.11-12.32) as potential risk factors of VCS in BS patients. For 4 BS patients with IVCS due to thrombosis, spectral CT found better contrast between IVC and thrombi at a low energy level of 40keV using virtual monoenergetic imaging than conventional images at 120kV. With a median follow-up of 3.3 years, the respective estimated 1- and 5-year survival rates were 96.3% and 94.2%, and respective estimated 1- and 5-year relapse-free rates were 93.9% and 78.0%. CONCLUSIONS: Male, early-onset BS, ESR >60 mm/hr, and pathergy reaction are potential risk factors of VCS in BS patients. Spectral CT is valuable in detecting thrombus in vena cava.

The efficacy and safety of anti-tumor necrosis factor agents in the treatment of intestinal Behcet's disease, a systematic review and meta-analysis.

BACKGROUND AND AIM: Behcet's disease is a systemic vasculitis that can involve gastrointestinal tract. This is a systematic review and meta-analysis evaluating the efficacy and safety of anti-tumor necrosis factor (TNF) agents in treating patients with intestinal Behcet's disease. METHODS: We conducted searches on PubMed, Embase, and Cochrane. Data from eligible studies were used to calculate the pooled estimate of proportions of clinical remission, mucosal healing at Months 3, 6, 12, and 24 as well as the pooled incidence of adverse drug reactions. And subgroup analysis based on the specific type of anti-TNF agents was performed. RESULTS: Of the 828 studies initially identified, 13 were included finally, all of which were single-arm cohort studies. The pooled proportions of clinical remission at Months 3, 6, 12, and 24 were 0.61 (95%CI 0.48-0.78), 0.51 (95%CI 0.40-0.66), 0.57 (95%CI 0.48-0.67), and 0.38 (95%CI 0.16-0.88), respectively. The pooled proportions of mucosal healing at Months 3, 6, 12, and 24 were 0.66 (95%CI 0.50-0.86), 0.82 (95%CI 0.48-0.98), 0.65 (95%CI 0.51-0.81), and 0.69 (95%CI 0.39-1.00), respectively. The pooled estimate of proportion of overall adverse drug reactions for infliximab was 0.22 (95%CI 0.07-0.69). CONCLUSIONS: Anti-TNF agents, including infliximab and adalimumab, were an efficient therapy for intestinal Behcet's disease. The safety of anti-TNF agents used in the treatment of intestinal Behcet's disease was acceptable.

Aberrant monocyte subsets in patients with Behçet's disease.

Monocytes are a versatile and dynamic population, but its implication in Behçet's Disease (BD) remains elusive. We investigated the proportion, phenotypical and functional alterations in classical monocytes (CM), intermediate monocytes (IM) and non-classical monocytes (NCM) subsets in BD. A higher IM and lower NCM population in BD patients were noted, closely correlated with disease activity, and rescued after treatment. CD11b and CD64 expression on CM, IM and NCM in BD were enhanced. BD CM promoted TNF-a and IL-6 production and facilitated Th1 differentiation. BD IM promoted IL-6 production. We further demonstrated a higher level of phosphorylated p65 (p-p65) in BD CM and increased p-p65 and p-p38 in BD IM. Our data highlighted the aberrant populations of IM and CM in BD, potentially implicated in BD' pathogenesis.

Iguratimod treatment reduces disease activity in early primary Sjögren's syndrome: An open-label pilot study.

OBJECTIVES: To evaluate the efficacy and safety of iguratimod in patients with early primary Sjögren's syndrome (pSS). METHODS: Twenty-seven disease-modifying antirheumatic drug-naive female patients met the revised American-European Consensus Group criteria for pSS were enrolled in this open-label pilot study. Patients were treated with iguratimod 25 mg twice a day for 24 weeks. The disease activity was assessed with European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at 12 and 24 weeks. Salivary and lacrimal gland function, laboratory, and subjective variables were also assessed. Generalized estimating equations were used to analyze parameters over time. RESULTS: ESSDAI (median, 5 versus 2 versus 2, p < .01), IgG (median, 26.6 versus 22.4 versus 21.4 g/L, p < .01) and rheumatoid factor (median, 119.9 versus 94.1 versus 83.8 lU/mL, p < .01) levels decreased significantly during iguratimod treatment. ESSPRI, salivary and lacrimal gland function, fatigue and health-related quality of life did not change during treatment. One patient experienced thrombocytopenia, and no other serious adverse effects were observed. CONCLUSION: In this study, iguratimod treatment is safe and effective for improving disease activity and laboratory parameters in early pSS patients.

Aberrant FcγRIIb and FcγRIII expression on monocytes from patients with Behçet's disease.

Behçet's disease (BD) patients have abnormal FcγR polymorphisms, the implication of which remains elusive. We examined FcγRIIb expression on neutrophils, monocytes, B cells, natural killer cells, dendritic cells and T cells, and FcγRI and FcγRIII expression on monocytes in BD patients and healthy controls using flow cytometry. We further stimulated monocytes with IgG and (or) lipopolysaccharide (LPS) and measured IL-6 and TNF-α production by enzyme-linked immunosorbent assay. We found that BD monocytes expressed a lower level of FcγRIIb and a higher level of FcγRIII, which were correlated with erythrocyte sedimentation rate and C-reactive protein and were rescued after treatment. Furthermore, LPS- and IgG-stimulated BD monocytes produced higher levels of IL-6 and TNF-α than HC monocytes. In summary, we found that BD monocytes downregulated FcγRIIb expression and upregulated FcγRIII expression, which were correlated with disease activity and potentially contributed to monocyte hyperactivation in BD.

Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis.

OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.

Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.

OBJECTIVES: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. METHODS: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. RESULTS: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results. CONCLUSIONS: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.