Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study.

BACKGROUND: To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP). METHODS: This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected. RESULTS: A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories. CONCLUSION: SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.

Prediction of progressive fibrosing interstitial lung disease in patients with systemic sclerosis: insight from the CRDC cohort study.

BACKGROUND: This study aims to establish a reliable prediction model of progressive fibrosing interstitial lung disease (PF-ILD) in patients with systemic sclerosis (SSc)-ILD, to achieve early risk stratification and to help better in preventing disease progression. METHODS: 304 SSc-ILD patients with no less than three pulmonary function tests within 6-24 months were included. We collected data at baseline and compared differences between SSc patients with and without PF-ILD. Least absolute shrinkage and selection operator regularisation regression and multivariable Cox regression were used to construct the prediction model, which were presented as nomogram and forest plot. RESULTS: Among the 304 patients with SSc-ILD included, 92.1% were women, with a baseline average age of 46.7 years. Based on the 28 variables preselected by comparison between SSc patients without PF-ILD group (n=150) and patients with SSc PF-ILD group (n=154), a 9-variable prediction model was constructed, including age≥50 years (HR 1.8221, p=0.001), hyperlipidemia (HR 4.0516, p<0.001), smoking history (HR 3.8130, p<0.001), diffused cutaneous SSc subtype (HR 1.9753, p<0.001), arthritis (HR 2.0008, p<0.001), shortness of breath (HR 2.0487, p=0.012), decreased serum immunoglobulin A level (HR 2.3900, p=0.002), positive anti-Scl-70 antibody (HR 1.9573, p=0.016) and usage of cyclophosphamide/mycophenolate mofetil (HR 0.4267, p<0.001). The concordance index after enhanced bootstrap resampling adjustment was 0.874, while the optimism-corrected Brier Score was 0.144 in internal validation. CONCLUSION: This study developed the first prediction model for PF-ILD in patients with SSc-ILD, and internal validation showed favourable accuracy and stability of the model.

Anemia and Low Body Mass Index in Axial Spondyloarthritis: Results from ChinaSpA, the Chinese Spondyloarthritis Registry.

INTRODUCTION: Anemia and malnutrition are recognized indicators of suboptimal physical condition in chronic inflammatory diseases. This study aimed to examine the association between anemia, low body mass index (BMI), and clinical outcomes in axial spondyloarthritis (axSpA). METHOD: This cross-sectional analysis utilized data from the multicenter ChinaSpA cohort. A total of 4146 participants with axSpA were categorized into four groups based on BMI and hemoglobin levels: those with both anemia and low BMI, those with anemia only, those with low BMI only, and those with neither condition. Logistic regression analyses were performed to analyze the association between anemia, low BMI, inflammation status, functional impairment, and disease activity. RESULTS: Anemia was present in 13.94%, low BMI in 11.99%, and both conditions in 2.15% of axSpA participants. Those with both anemia and low BMI showed significantly higher levels of inflammation (hypersensitive C-reactive protein [hsCRP] 30.60 mg/L vs. 8.44 mg/L), functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI] 3.80 vs. 2.10), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 4.52 ± 2.04 vs. 3.67 ± 2.21; Ankylosing Spondylitis Disease Activity Score calculated with C-reactive protein [ASDAS_CRP] 3.51 ± 1.10 vs. 2.62 ± 1.21) compared to those without these conditions. After adjusting for sex and age, significant associations were observed between elevated hsCRP levels and the presence of low BMI (odds ratio [OR] 1.44, 95% CI 1.17-1.78), anemia (OR 1.91, 95% CI 1.56-2.32), and their concurrent presence (OR 3.59, 95% CI 2.22-5.80). Similarly, increased BASFI was significantly associated with low BMI (OR 1.57, 95% CI 1.25-1.97), anemia (OR 1.47, 95% CI 1.19-1.80), and their combination (OR 3.11, 95% CI 2.02-4.78). CONCLUSION: All-cause anemia and low BMI are prevalent complications in patients with axSpA, exhibiting a significant correlation with elevated inflammation status and functional impairment. The simultaneous occurrence of anemia and low BMI particularly exacerbates clinical outcomes, emphasizing the critical role of comprehensive nutritional assessment and management in the therapeutic strategy for axSpA.

Genetic link between primary biliary cholangitis and connective tissue diseases in European populations: A two-sample Mendelian randomization study.

BACKGROUND: An association between primary biliary cholangitis (PBC) and connective tissue diseases (CTDs) [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), systemic sclerosis (SSc)] has been found in observational studies. However, the direction causality is unclear. The aim of this study was to assess the causality between PBC and CTDs and to promote early screening, pre-emptive therapy, and accurate stratification. METHODS: A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between PBC [Genome-Wide Association Study (GWAS) meta-analysis, 8021 cases/16498 controls], and SLE (GWAS meta-analysis, 8021 cases/16489 controls), RA(FinnGen, 6236 cases/14727 controls), SS(FinnGen, 2495 cases/365533 controls), SSc (FinnGen, 302 cases/213145 controls). Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by four sensitivity analyses to assess the robustness of the results. RESULTS: The IVW revealed that genetically predicted PBC increased the risk of SLE [odd's ratio (OR) = 1.43, 95% confidence interval (CI) 1.30-1.58, P < 0.001]), RA (OR = 1.09, 95%CI1.04-1.14, P<0.001), and SS (OR = 1.18, 95%CI1.12-1.24, P<0.001), but not that of SSc. In addition, no association was observed between CTDs as an exposure and PBC. Sensitivity analyses did not reveal horizontal pleiotropy. CONCLUSIONS: Our study provided new genetic evidence for a causal relationship between PBC and CTDs. PBC increased the risk of SLE, RA, and SS. Our findings highlighted the importance of active screening and intervention for CTDs in patients with PBC.

Sex-specific differences in patients with psoriatic arthritis:a nationwide study from the Chinese Registry of Psoriatic Arthritis (CREPAR IV).

OBJECTIVES: To elucidate the sex-specific differences in demographic features, clinical characteristics, and quality of life in Chinese patients with psoriatic arthritis (PsA). METHODS: A total of 1,074 patients with PsA registered between December 2018 and June 2021 from the Chinese REgistry of Psoriatic ARthritis (CREPAR) cohort were selected. The baseline data on demographics, clinical characteristics, commonly used laboratory tests, comorbidities, and quality of life assessments were collected for this cross-sectional analysis. RESULTS: A total of 1,074 patients were included in this study, 585 (54.47%) of them were male and 489 (45.53%) were female. The age at PsA onset in male patients was earlier than that in female patients (38.10 ± 12.79 vs 40.37 ± 13.41, p = 0.005). For clinical characteristics, male patients presented with higher rates of axial involvement (43.89% vs 37.74%, p = 0.044) and nail involvement (66.15% vs 58.08%, p = 0.006), while female patients presented with higher rates of peripheral arthritis (89.57% vs 83.93%, p = 0.007). For laboratory tests, men presented with a higher percentage of HLA-B27 positivity than women (24.65% vs 16.70%, p = 0.002) and had higher levels of CRP (median 9.70 vs 5.65, p < 0.001). Regarding disease assessment indices, male patients scored higher in PASI and BASFI (median 5.00 vs 3.00, p = 0.007 and 1.80 vs 1.40, p = 0.012, respectively). No sex difference was found in rates of achieving remission. Factors associated with disease remission were also analyzed in both sexes. CONCLUSION: Demographic and clinical characteristics tend to vary between male and female patients with PsA. Male patients reported more functional limitations in daily life. Key Points • The demographic and clinical features vary greatly between male and female patients with PsA. • Male patients reported more functional burden in daily life as measured by BASFI.

Efficacy and safety of telitacicept in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled, phase 2 trial.

OBJECTIVE: To evaluate the efficacy and safety of telitacicept in adult patients with primary SS (pSS) in a phase II randomized double-blind placebo-controlled trial. METHODS: Patients with pSS with positive anti-SSA antibody and ESSDAI ≥ 5 were randomly assigned, in a 1:1:1 ratio, to receive weekly subcutaneous telitacicept 240 mg, 160 mg, or placebo for 24 weeks. The primary end point was the change from baseline in the ESSDAI at week 24. Safety was monitored. RESULTS: A total of 42 patients were enrolled and randomized (n = 14 per group). Administration of telitacicept 160 mg resulted in a significant reduction in ESSDAI score from baseline to week 24 compared with placebo (P < 0.05). The placebo-adjusted least-squares mean change from baseline was -4.3 (95% CI -7.0, -1.6; P = 0.002). While, mean change of ESSDAI in telitacicept 240 mg was -2.7(-5.6-0.1) with no statistical difference when compared that in placebo group (P = 0.056). In addition, MFI-20 and serum immunoglobulins decreased significantly (P < 0.05) at week 24 in both telitacicept groups compared with placebo. No serious adverse events were observed in the telitacicept treating group. CONCLUSION: Telitacicept showed clinical benefits and good tolerance and safety in the treatment of pSS. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04078386.

Decoding the mitochondrial connection: development and validation of biomarkers for classifying and treating systemic lupus erythematosus through bioinformatics and machine learning.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease characterized by clinical and pathological diversity. Mitochondrial dysfunction has been identified as a critical pathogenetic factor in SLE. However, the specific molecular aspects and regulatory roles of this dysfunction in SLE are not fully understood. Our study aims to explore the molecular characteristics of mitochondria-related genes (MRGs) in SLE, with a focus on identifying reliable biomarkers for classification and therapeutic purposes. METHODS: We sourced six SLE-related microarray datasets (GSE61635, GSE50772, GSE30153, GSE99967, GSE81622, and GSE49454) from the Gene Expression Omnibus (GEO) database. Three of these datasets (GSE61635, GSE50772, GSE30153) were integrated into a training set for differential analysis. The intersection of differentially expressed genes with MRGs yielded a set of differentially expressed MRGs (DE-MRGs). We employed machine learning algorithms-random forest (RF), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) logistic regression-to select key hub genes. These genes' classifying potential was validated in the training set and three other validation sets (GSE99967, GSE81622, and GSE49454). Further analyses included differential expression, co-expression, protein-protein interaction (PPI), gene set enrichment analysis (GSEA), and immune infiltration, centered on these hub genes. We also constructed TF-mRNA, miRNA-mRNA, and drug-target networks based on these hub genes using the ChEA3, miRcode, and PubChem databases. RESULTS: Our investigation identified 761 differentially expressed genes (DEGs), mainly related to viral infection, inflammatory, and immune-related signaling pathways. The interaction between these DEGs and MRGs led to the identification of 27 distinct DE-MRGs. Key among these were FAM210B, MSRB2, LYRM7, IFI27, and SCO2, designated as hub genes through machine learning analysis. Their significant role in SLE classification was confirmed in both the training and validation sets. Additional analyses included differential expression, co-expression, PPI, GSEA, immune infiltration, and the construction of TF-mRNA, miRNA-mRNA, and drug-target networks. CONCLUSIONS: This research represents a novel exploration into the MRGs of SLE, identifying FAM210B, MSRB2, LYRM7, IFI27, and SCO2 as significant candidates for classifying and therapeutic targeting.

Development and external validation of a prediction model for venous thromboembolism in systemic lupus erythematosus.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of venous thromboembolism (VTE). We conducted this study to develop a risk score algorithm for VTE in patients with SLE that provides individualised risk estimates. METHODS: We developed a clinical prediction model of VTE in 4502 patients with SLE based on the Chinese SLE Treatment and Research group cohort (CSTAR) from January 2009 to January 2020 and externally validated in 3780 patients with SLE in CSTAR from January 2020 to January 2022. Baseline data were obtained and VTE events were recorded during the follow-up. The prediction model was developed to predict VTE risk within 6 months in patients with SLE, using multivariate logistic regression and least absolute shrinkage and selection operator. SLE-VTE score and nomogram were established according to the model. RESULTS: A total of 4502 patients included in the development cohort, 135 had VTE events. The final prediction model (SLE-VTE score) included 11 variables: gender, age, body mass index, hyperlipidaemia, hypoalbuminaemia, C reactive protein, anti-ß2GPI antibodies, lupus anticoagulant, renal involvement, nervous system involvement and hydroxychloroquine, with area under the curve of 0.947 and 0.808 in the development (n=4502) and external validation cohort (n=3780), respectively. According to the net benefit and predicted probability thresholds, we recommend annual screening of VTE in high risk (≥1.03%) patients with SLE. CONCLUSION: Various factors are related to the occurrence of VTE in patients with SLE. The proposed SLE-VTE risk score can accurately predict the risk of VTE and help identify patients with SLE with a high risk of VTE who may benefit from thromboprophylaxis.

Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) incidence is higher in systemic lupus erythematosus (SLE) patients than the general population, but the molecular mechanisms behind this link remain ambiguous. The aim of this study was to investigate shared gene signatures and molecular pathways between SLE and DLBCL. METHODS: We procured expression profiles of SLE and DLBCL from public databases and identified common differentially expressed genes (DEGs). Functional pathway enrichment and protein-protein interaction (PPI) analyses were performed on these shared genes. The molecular complex detection technology (MCODE) and eXtreme Gradient Boosting (XGBoost) machine learning algorithm were used to select core shared genes, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis. RESULTS: We identified 54 DEGs as shared genes, among which CD177, CEACAM1, GPR84 and IFIT3 were identified as core shared genes. These genes showed strong associations with inflammatory and immune response pathways. We found a significant positive correlation between GPR84 and IFIT3 expression levels and the immune microenvironment. Decreased expression levels of GPR84 and IFIT3 were linked to enhanced immune therapy sensitivity, potentially due to lower dysregulation scores during low expression. We also discovered that TP53 mutations might elevate CD177 and GPR84 expression and that reduced expression levels of GPR84 and IFIT3 were linked with better overall survival and progression-free survival in DLBCL patients. CONCLUSIONS: Our study provides valuable insights into the shared molecular mechanisms underpinning the pathogenesis of SLE and DLBCL. These findings could potentially offer new biomarkers and therapeutic targets for SLE and DLBCL.

Chinese Registry of Psoriatic Arthritis (CREPAR): I. Clinical characteristics of Chinese patients with psoriatic arthritis.

AIM: To describe the clinical characteristics of Chinese patients with psoriatic arthritis (PsA) using the data recorded in the Chinese Registry of Psoriatic Arthritis (CREPAR). METHODS: This is a cross-sectional study based on the CREPAR registry, which is a prospective registry founded in December 2018. Data regarding clinical characteristics and treatment of patients were collected during every visit. Data recorded at enrollment were extracted, analyzed, and compared with data in other registries or cohorts. RESULTS: A total of 1074 patients were registered from December 2018 to June 2021. Of these, 929 (86.5%) patients had a history of peripheral arthritis, and 844 patients (78.6%) had peripheral arthritis at enrollment, of which polyarthritis is the most common subtype. Axial involvement was present in 39.9% of patients, and 50 (4.7%) patients had axial involvement only. More than half of the patients (55.4%) had at least two musculoskeletal presentations at enrollment. The prevalence of low disease activity and remission according to DAPSA were 26.4% and 6.8%, respectively. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs were used in 64.9% and 29.1% of patients, respectively. Among patients with different musculoskeletal presentations, patients with dactylitis had the highest proportion of nonsteroidal anti-inflammatory and csDMARD use. The proportion of patients receiving bDMARDs was highest in axial PsA. CONCLUSION: The CREPAR registry has provided information on Chinese patients with PsA. Compared with data in other registries or cohorts, the disease activity of patients in CREPAR was higher, and the proportion of bDMARD use was lower.

Identification of NETs-related biomarkers and molecular clusters in systemic lupus erythematosus.

Neutrophil extracellular traps (NETs) is an important process involved in the pathogenesis of systemic lupus erythematosus (SLE), but the potential mechanisms of NETs contributing to SLE at the genetic level have not been clearly investigated. This investigation aimed to explore the molecular characteristics of NETs-related genes (NRGs) in SLE based on bioinformatics analysis, and identify associated reliable biomarkers and molecular clusters. Dataset GSE45291 was acquired from the Gene Expression Omnibus repository and used as a training set for subsequent analysis. A total of 1006 differentially expressed genes (DEGs) were obtained, most of which were associated with multiple viral infections. The interaction of DEGs with NRGs revealed 8 differentially expressed NRGs (DE-NRGs). The correlation and protein-protein interaction analyses of these DE-NRGs were performed. Among them, HMGB1, ITGB2, and CREB5 were selected as hub genes by random forest, support vector machine, and least absolute shrinkage and selection operator algorithms. The significant diagnostic value for SLE was confirmed in the training set and three validation sets (GSE81622, GSE61635, and GSE122459). Additionally, three NETs-related sub-clusters were identified based on the hub genes' expression profiles analyzed by unsupervised consensus cluster assessment. Functional enrichment was performed among the three NETs subgroups, and the data revealed that cluster 1 highly expressed DEGs were prevalent in innate immune response pathways while that of cluster 3 were enriched in adaptive immune response pathways. Moreover, immune infiltration analysis also revealed that innate immune cells were markedly infiltrated in cluster 1 while the adaptive immune cells were upregulated in cluster 3. As per our knowledge, this investigation is the first to explore the molecular characteristics of NRGs in SLE, identify three potential biomarkers (HMGB1, ITGB2, and CREB5), and three distinct clusters based on these hub biomarkers.

Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII.

BACKGROUND: Avascular necrosis is a common organ damage in SLE patients, which can influence patients' life quality. Conflicting results exist in risk factors of AVN in SLE patients. The aim of this study was to illustrate risk factors predicting the occurrence of avascular necrosis (AVN), also known as osteonecrosis, in systemic lupus erythematosus (SLE) patients in Chinese SLE Treatment and Research Group (CSTAR), a multi-center cohort of Chinese SLE patients. METHODS: SLE patients in CSTAR without existing AVN at registration were included. At least two follow-ups and an observation period of no less than 2 years for AVN event were required. Univariate and multivariate Cox regression analyses were used to evaluate risk factors for AVN in SLE patients. Coefficient B was transformed to risk score for the development of a risk stratification model. RESULTS: One hundred six (2.59%) of 4091 SLE patients were diagnosed AVN during follow-ups of no less than 2 years. Multi-variate Cox regression analysis suggested that SLE onset age ≤ 30 (HR 1.616, p 0.023), arthritis (HR 1.642, p 0.018), existing organ damage (SDI ≥ 1) at registration (HR 2.610, p < 0.001), positive anti-RNP (HR 1.709, p 0.006), and high glucocorticoid maximum daily dose at registration (HR 1.747, p 0.02) were independent risk factors. A risk stratification system was developed according to the risk factors, and patients were divided into high risk (3-6) and low risk (0-2). The AUC of 0.692 indicated moderate discrimination. The calibration curve in internal validation was drawn. CONCLUSION: Patients with SLE onset age ≤ 30, arthritis, existing organ damage (SDI ≥ 1) at registration, positive anti-RNP, and high glucocorticoid maximum daily dose at registration are at high risk for AVN and require attention.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR).

BACKGROUND: The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts. METHODS: Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts. RESULTS: In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use. CONCLUSIONS: Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

Predictors of relapse in Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TAK) is a large-vessel vasculitis with high relapse rate. Longitudinal studies identifying risk factors of relapse are limited. We aimed to analyze the associated factors and develop a risk prediction model for relapse. METHODS: We analyzed the associated factors for relapse in a prospective cohort of 549 TAK patients from the Chinese Registry of Systemic Vasculitis cohort between June 2014 and December 2021 using univariate and multivariate Cox regression analyses. We also developed a prediction model for relapse, and stratified patients into low-, medium-, and high-risk groups. Discrimination and calibration were measured using C-index and calibration plots. RESULTS: At a median follow-up of 44 (IQR 26-62) months, 276 (50.3%) patients experienced relapses. History of relapse (HR 2.78 [2.14-3.60]), disease duration <24 months (HR 1.78 [1.37-2.32]), history of cerebrovascular events (HR 1.55 [1.12-2.16]), aneurysm (HR 1.49 [1.10-2.04], ascending aorta or aortic arch involvement (HR 1.37 [1.05-1.79]), elevated high-sensitivity C-reactive protein level (HR 1.34 [1.03-1.73]), elevated white blood cell count (HR 1.32 [1.03-1.69]), and the number of involved arteries ≥6 (HR 1.31 [1.00-1.72]) at baseline independently increased the risk of relapse and were included in the prediction model. The C-index of the prediction model was 0.70 (95% CI 0.67-0.74). Predictions correlated with observed outcomes on the calibration plots. Compared to the low-risk group, both medium and high-risk groups had a significantly higher relapse risk. CONCLUSIONS: Disease relapse is common in TAK patients. This prediction model may help to identify high-risk patients for relapse and assist clinical decision-making.

Hyperglobulinemia predicts increased risk of mortality in primary Sjögren's syndrome: Based on a Chinese multicentre registry.

OBJECTIVE: To investigate whether primary Sjögren's syndrome (pSS) patients with hyperglobulinemia have an increased risk of all-cause mortality. METHODS: Patients who registered in the Chinese Rheumatism Data Centre from May 2016 to July 2021 and met the 2002 American European Consensus Group criteria or 2016 American College of Rheumatology /European League Against Rheumatism classification criteria for Sjögren's syndrome were included. Hyperglobulinemia was defined as any elevated serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM). The primary outcome was all-cause death. Data for demographic and clinical characteristics, laboratory results, disease activity, damage scores, and treatments were evaluated. RESULTS: A total of 9527 pSS patients were included in the analysis, of whom 4236 (44.5%) had at least one kind of elevated immunoglobulin level among IgG, IgA, and IgM. Patients with hyperglobulinemia had a significantly increased risk of death (crude hazard ratio 2.60; 95% confidence interval 1.91-3.55; adjusted hazard ratio 1.90; 95% confidence interval 1.20-3.01). The risk of death was positively correlated with IgG level (P trend <.001). The 5-, 10-, and 15-year survival rates of patients with hyperglobulinemia were 96.9%, 92.3%, and 87.9%, respectively, and significantly lower than the corresponding rates of 98.8%, 97.9%, and 96.4% in patients without hyperglobulinemia. CONCLUSIONS: Hyperglobulinemia is an independent risk factor for increased all-cause mortality in pSS patients. The risk of death is positively correlated with IgG level.

The star target in SLE: IL-17.

PURPOSE: The purpose of this review is to discuss the significance of IL-17 in SLE and the potential of IL-17-targeted therapy. BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs and tissues throughout the body. It is characterized by overactive B and T cells and loss of immune tolerance to autoantigens. Interleukin-17 (IL-17) is a cytokine that promotes inflammation and has been implicated in the pathogenesis of several autoimmune diseases as well as inflammatory diseases. In in vitro cellular experiments in lupus susceptible mice or SLE patients, there is substantial evidence that IL-17 is a highly promising therapeutic target. METHODS: We searched papers from PubMed database using the search terms, such as interleukin-17, systemic lupus erythematosus, treatment targets, T cells, lupus nephritis, and other relevant terms. RESULTS: We discuss in this paper the molecular mechanisms of IL-17 expression, Th17 cell proliferation, and the relationship between IL-17 and Th17. The significance of IL-17 in SLE and the potential of IL-17-targeted therapy are further discussed in detail. CONCLUSION: IL-17 has a very high potential for the development as a star target in SLE.

Analysis of the risk factors for end­stage renal disease and mortality in ANCA-associated vasculitis: a study from a single center of the Chinese Rheumatism Data Center.

OBJECTIVE: The purpose of this study was to describe the clinical features of AAV and identify possible risk factors for end-stage renal disease (ESRD) and mortality in AAV based on the experience of a single center in China. METHODS: A prospective cohort study of AAV was conducted based on data acquired by the Chinese Rheumatism Data Center (CRDC). The cohort involved 140 patients diagnosed with AAV in the Second Affiliated Hospital of Nanchang University from January 2013 to April 2022. Clinical characteristics and prognostic data were prospectively collected. The patients were divided into an ESRD group and a non-ESRD group, a death group and a survival group, Then, univariate and multivariate COX regression models were used to determine the risk factors associated with ESRD and mortality by AAV. RESULTS: Multivariate Cox regression results showed that high initial serum creatinine (hazard ratio (HR) = 1.001, 95% confidence interval (CI): 1.000-1.002, P = 0.024), high initial Birmingham vasculitis activity score (BVAS) (HR = 1.081, 95% CI: 1.027-1.138, P = 0.003), and the need for dialysis treatment (HR = 4.918, 95% CI: 1.727-14.000, P = 0.003) were independent risk factors for the progression of ESRD in AAV patients. Multivariate Cox regression results showed that alveolar hemorrhage (HR = 3.846, 95% CI: 1.235-11.973, P = 0.020), interstitial lung disease (HR = 4.818, 95% CI: 1.788-12.982, P = 0.002), and low initial estimated glomerular filtration rate (EGFR) (HR = 0.981, 95% CI: 0.968-0.995, P = 0.009) were independent risk factors for the prediction of death in AAV patients. CONCLUSION: These findings suggest that high initial serum creatinine, a high initial BVAS score, and the need for dialysis were independent risk factors for the progression of ESRD in AAV patients. Alveolar hemorrhage, interstitial lung disease, and low initial EGFR were independent risk factors for death. Key Points • The risk factors for ESRD in AAV determined in this study are high initial serum creatinine, a high initial BVAS score, and the need for dialysis. • The risk factors for mortality in AAV are alveolar hemorrhage, interstitial lung disease, and low initial EGFR.

Renal tubular acidosis and associated factors in patients with primary Sjögren's syndrome: a registry-based study.

OBJECTIVES: To investigate the clinical features and factors associated with primary Sjögren's syndrome (pSS)-associated renal tubular acidosis (RTA). METHOD: This case-control study was based on a multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients with pSS, including those with RTA and those without renal involvement, between May 2016 and March 2020 were included in the analysis. Demographic, clinical, and laboratory data were also collected. Univariate and multivariate logistic regression analyses were used to identify factors that were associated with pSS-RTA. RESULTS: This study included 257 pSS patients with RTA and 4222 patients without renal involvement. Significantly younger age at disease onset (40.1 ± 14.1 vs. 46.2 ± 13.1 years, P < 0.001), longer diagnosis interval (15.0 interquartile range [IQR] [1.0, 48.0] vs. 6.0 IQR [0, 34.0] months, P < 0.001), higher EULAR Sjögren's syndrome disease activity index (9 IQR [5, 15] vs. 3 IQR [0, 8], P < 0.001), and a higher prevalence of decreased estimated glomerular filtration rate (25.0% vs. 6.6%, P < 0.001) were observed in pSS patients with RTA than in those without renal involvement. Factors that were independently associated with pSS-RTA included age at disease onset ≤ 35 years (odds ratio [OR] 3.00, 95% confidence interval [CI] 2.27-3.97), thyroid disorders (OR 1.49, 95% CI 1.04-2.14), subjective dry mouth (OR 3.29, 95% CI 1.71-6.35), arthritis (OR 1.57, 95% CI 1.10-2.25), anti-SSB antibody positivity (OR 1.80, 95% CI 1.33-2.45), anemia (OR 1.67, 95% CI 1.26-2.21), elevated alkaline phosphatase level (OR 2.14, 95% CI 1.26-3.65), decreased albumin level (OR 1.61, 95% CI 1.00-2.60), and elevated erythrocyte sedimentation rate (OR 1.78, 95% CI 1.16-2.73). CONCLUSIONS: Delayed diagnosis and decreased kidney function are common in pSS patients with RTA. pSS should be considered in patients with RTA, and early recognition and treatment may be useful in slowing the deterioration of renal function in patients with pSS-RTA. Key Points • pSS patients with RTA have earlier disease onset and higher disease activity than pSS patients without RTA, but the diagnosis was frequently delayed. • Decreased kidney function are common in pSS patients with RTA. • Sjögren's syndrome should be considered in young female patients with unexplained RTA, whereas RTA should be screened in pSS patients with early disease onset and elevated ALP level.

Comparing clinical characteristics of systemic sclerosis with or without interstitial lung disease: A cross-sectional study from a single center of the Chinese Rheumatism Data Center.

Background: We aimed to compare the clinical characteristics of patients with systemic sclerosis (SSc) with or without interstitial lung disease (ILD) to identify relationships with the presence of ILD in SSc at a single center in China. Methods: A cross-sectional study was conducted using retrospective data from the Chinese Rheumatology Data Center. Patients diagnosed with SSc at the Second Affiliated Hospital of Nanchang University between 2013 and 2022 were included. Demographic and clinical characteristics were compared between patients with SSc with and without ILD. Logistic regression analyses were performed to explore these associations. Results: A total of 227 patients with SSc were included (male:female ratio = 1:4.82), of which 121 (53.3%) were accompanied with ILD. SSc patients with ILD had a higher percentage of diffuse cutaneous systemic sclerosis (dcSSc), sclerodactyly, loss of finger pad, muscle involvement, left ventricular diastolic dysfunction (LVDD), and pulmonary hypertension (PAH), elevated Krebs von den Lungen-6 (KL-6), and elevated ferritin than those without ILD, and a higher modified Rodnan skin score (mRSS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (all P < 0.05). Antinuclear antibody (ANA) and anti-scleroderma-70 (anti-Scl-70) positivity was presented frequently in SSc patients with ILD, while SSc patients without ILD were more often anti-centromere antibody (ACA) positive (all P < 0.05). On the multivariable analysis, muscle involvement [OR 2.551 (95% CI 1.054-6.175), P = 0.038], LVDD [OR 2.360 (95% CI 1.277-4.361), P = 0.006], PAH [OR 9.134 (95% CI 2.335-35.730), P = 0.001], dcSSc [OR 2.859 (95% CI 1.489-5.487), P = 0.002], PLR [OR 1.005 (95% CI 1.001-1.008), P = 0.020], elevated KL-6 [OR 2.033 (95% CI 1.099-3.763), P = 0.024], and anti-Scl-70 [OR 3.101 (95% CI 1.647-5.840), P < 0.001] were statistically significant associations with SSc patients with ILD. Conclusion: Systemic sclerosis was found mainly in females. Several important differences in clinical and laboratory characteristics have been demonstrated between SSc patients with or without ILD. Muscle involvement, LVDD, PAH, dcSSc, PLR, elevated KL-6, and Anti-Scl-70 antibody may be associated with SSc in patients with ILD.