Predicting the risk of cardiovascular and cerebrovascular event in systemic lupus erythematosus: a Chinese SLE treatment and research group study XXVI.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular and cerebrovascular events (CCEs). Furthermore, CCE was a significant factor contributing to mortality in patients with SLE. However, no clinical model exists that can predict which patients are at high risk. The purpose of this study was to develop a practical model for predicting the risk of CCE in people with SLE. METHODS: This study was based on the Chinese SLE Treatment and Research Group cohort. A total of 2399 patients, who had a follow-up period of over 3 years and were diagnosed with SLE for less than 1 year at the start of the study, were included. Cox proportional hazards regression and least absolute shrinkage and selection operator regression were used to establish the model. Internal validation was performed, and the predictive power of the model was evaluated. RESULTS: During the follow-up period, 93 patients had CCEs. The prediction model included nine variables: male gender, smoking, hypertension, age of SLE onset >40, cutaneous involvement, arthritis, anti-ß2GP1 antibody positivity, high-dose glucocorticoids and hydroxychloroquine usage. The model's C index was 0.801. Patients with a prognostic index over 0.544 were classified into the high-risk group. CONCLUSION: We have developed a predictive model that uses clinical indicators to assess the probability of CCE in patients diagnosed with SLE. This model has the ability to precisely predict the risk of CCE in patients with SLE. We recommended using this model in the routine assessment of patients with SLE.

The role of imbalanced CD226/TIGIT on activated peripheral double-negative T cells in the pathogenesis of primary Sjögren's syndrome.

OBJECTIVES: To explore whether the balance of CD226 and TIGIT is disturbed in CD3+CD56-TCRαß+CD4-CD8- (DN) T cells and have a better understanding of the potential role of DN T cells in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: The percentage of DN T cells as well as the expression of CD226 and TIGIT was identified by flowmetry. After in vitro stimulation, we further detected the expression of activation and cytotoxic marker, as well as intracellular cytokines secreted by DN T cells. RESULTS: DN T cells were found to expand in the peripheral blood of pSS patients (1.77±0.66%) and correlate with IgG (r=0.451, p<0.05), C3 (r=-0.438, p<0.05) and C4 (r=-0.470, p<0.05). Imbalanced CD226/TIGIT was observed on peripheral DN T cells of pSS patients, especially the overexpression of inhibitory immunoreceptor TIGIT. The expression ratio of TIGIT and CD226 on DN T cells was elevated in pSS patients and correlated with ESSDAI scores≥5 (r=0.743, p<0.05). Besides, these DN T cells were found to be activated and show strong cytotoxicity. CONCLUSIONS: The balance between CD226 and TIGIT on DN T cells was disturbed and correlated with the disease activity in pSS patients, which may be implicated in the pathogenesis of pSS.

Tofacitinib versus thalidomide for mucocutaneous lesions of systemic lupus erythematosus: A real-world CSTAR cohort study XXVII.

OBJECTIVE: Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE. METHODS: This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points. RESULTS: At 3 and 6 months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group. CONCLUSIONS: Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile.

The Etiology of Intracranial Artery Stenosis in Autoimmune Rheumatic Diseases-An Observational High-Resolution Magnetic Resonance Imaging Study.

BACKGROUND AND PURPOSE: Autoimmune rheumatic diseases (AIRD) can cause intracranial artery stenosis (ICAS) and lead to stroke. This study aimed to characterize patients with ICAS associated with AIRD. MATERIALS AND METHODS: Utilizing data from a high-resolution magnetic resonance imaging (HRMRI) database, we retrospectively reviewed AIRD patients with ICAS. Stratification into vasculitis, atherosclerosis, and mixed athero-vasculitis subtypes was based on imaging findings, followed by a comparative analysis of clinical characteristics and outcomes across these subgroups. RESULTS: Among 139 patients (45.1±17.3 years; 64.7% females), 56 (40.3%) were identified with vasculitis, 57 (41.0%) with atherosclerosis, and 26 (18.7%) with mixed athero-vasculitis. The average interval from AIRD-onset to HRMRI was 5 years. Patients with vasculitis presented with a younger age of AIRD-onset (34.5±19.4 years), nearly ten years earlier than other groups (P=0.010), with a higher artery occlusion incidence (44.6% vs. 21.1% and 26.9%, P=0.021). Patients with atherosclerosis showed the highest cardiovascular risk factor prevalence (73.7% vs. 48.2% and 61.5%, P=0.021) but lower intracranial artery wall enhancement instances (63.2% vs. 100% in others, P<0.001). The mixed athero-vasculitis group, predominantly male (69.2% vs. 30.4% and 25.6%, P<0.001), exhibited the most arterial involvement (5 arteries per person vs. 3 and 2, P=0.001). Over an average 21-month follow-up, 23 (17.0%) patients experienced stroke events, and 8 (5.9%) died, with the mixed athero-vasculitis group facing the highest risk of stroke events (32.0%) and the highest mortality (12.0%). CONCLUSIONS: Intracranial arteries are injured and lead to heterogeneous disease courses when exposed to AIRD and cardiovascular risk factors. While atherosclerosis acceleration is common, vasculitis may further contribute to early-developed occlusion and multiple artery involvement. Varied intracranial arteriopathies may result in different outcomes. ABBREVIATIONS: ICAS = intracranial artery stenosis; AIRD = Autoimmune rheumatic diseases; HRMRI = high-resolution magnetic resonance imaging.

Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.

OBJECTIVES: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. METHODS: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. RESULTS: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. CONCLUSION: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.

Belimumab in early systemic lupus erythematosus: A propensity score matching analysis.

OBJECTIVE: This study aimed to evaluate the clinical efficacy of belimumab in patients with early systemic lupus erythematosus (SLE), defined as having a disease duration of less than 6 months. METHODS: We retrospectively identified patients with SLE in the early stage who received belimumab and standard of care (belimumab group) or standard of care alone (control group) since September 2020. Propensity score matching (PSM) was used to reduce potential bias. The primary endpoint was lupus low disease activity status (LLDAS) at weeks 12 and 24. The secondary endpoints were remission and the proportion of glucocorticoid dose tapering to 7.5 mg/day. The efficacy of belimumab in patients with lupus nephritis was also assessed. RESULTS: Out of 111 eligible patients, 16 patients in the belimumab group and 31 patients in the control group were identified by 1:2 PSM. At week 24, a significantly higher proportion of individuals achieved low disease activity state (LLDAS) in the belimumab group compared to the control group (56.3% vs. 19.4%, OR = 5.357, 95% CI = 1.417 to 20.260, p = 0.013). Furthermore, more patients in the belimumab group were reduced to low-dose glucocorticoid ( ≤ 7.5 mg/day) at week 24 (75.0% vs. 35.5%, OR = 5.182, 95%CI = 1.339 to 20.058, p = 0.017). Significant improvements in Patient Global Assessment scores were observed at Week 12 and 24 for those treated with belimumab compared to controls. In a subgroup analysis evaluating the efficacy of belimumab in patients with lupus nephritis, 42.9% of the seven individuals treated with belimumab achieved a complete renal response (CRR) by Week 24, and no instances of disease relapse were observed. CONCLUSIONS: In SLE patients with a disease duration of less than 6 months, belimumab treatment can promote LLDAS achievement and reduce glucocorticoid dose, leading to a better prognosis. Introducing belimumab in the early stage of SLE may be a beneficial decision.

Identification of Lupus-Associated Genes in the Pathogenesis of Pre-eclampsia Via Bioinformatic Analysis.

Pre-eclampsia (PE) is a severe pregnancy complication that is more common in patients with systemic lupus erythematosus (SLE). Although the exact causes of these conditions are not fully understood, the immune system plays a key role. To investigate the connection between SLE and PE, we analyzed genes associated with SLE that may contribute to the development of PE. We collected 9 microarray data sets from the NCBI GEO database and used Limma to identify the differentially expressed genes (DEGs). In addition, we employed weighted gene co-expression network analysis (WGCNA) to pinpoint the hub genes of SLE and examined immune infiltration using Cibersort. By constructing a protein-protein interaction (PPI) network and using CytoHubba, we identified the top 20 PE hub genes. Subsequently, we created a nomogram and conducted a receiver operating characteristic (ROC) analysis to predict the risk of PE. Our analysis, including gene set enrichment analysis (GSEA) and PE DEGs enrichment analysis, revealed significant involvement in placenta development and immune response. Two pivotal genes, BCL6 and MME, were identified, and their validity was confirmed using 5 data sets. The nomogram demonstrated good diagnostic performance (AUC: 0.82-0.96). Furthermore, we found elevated expression levels of both genes in SLE peripheral blood mononuclear cells (PBMCs) and PE placental specimens within the case group. Analysis of immune infiltration in the SLE data set showed a strong positive correlation between the expression of both genes and neutrophil infiltration. BCL6 and MME emerged as crucial genes in lupus-related pregnancies associated with the development of PE, for which we devised a nomogram. These findings provide potential candidate genes for further research in the diagnosis and understanding of the pathophysiology of PE.

Incidence and prevalence of systemic lupus erythematosus in urban China, 2013-2017: A nationwide population-based study.

Systemic lupus erythematosus (SLE) is becoming a growing public health concern due to increasing disease and economic burdens. Epidemiological information about SLE, especially its incidence rate, is limited in developing countries. In the current study, we sought to investigate the incidence, prevalence, and economic burdens of SLE in urban China. We conducted a nationwide population-based cohort study using databases from Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance between 2013 and 2017, covering approximately 300 million residents in 23 provincial regions in China. Incidence rate and prevalence were standardized by age and gender to China's 2010 national census data. Additionally, we calculated the average annual costs and hospital visit rates. A total of 132,258 SLE patients were identified during the study period, with a mean age of 43.03 years (standard deviation: 15.29 years). Of these patients, 81.33% were women. In 2017, the standardized incidence rate of SLE in China was 14.09 (95% confidence interval (CI), 11.95-16.41) per 100,000 person-years, with a higher incidence in women than in men (26.41 vs. 5.92 per 100,000 person-years). Standardized prevalence in 2017 was 47.61 (41.77-53.83), 94.16 (80.67-108.69), and 17.86 (13.84-22.38) per 100,000 people in the overall, female, and male populations, respectively. The average annual rates of increase in prevalence were 21.50%, 19.72%, and 25.67% from 2013 to 2017 in the overall, female, and male populations, respectively. The age-specific incidence rates peaked at 30-49 years old in women and 40-59 years old in men. SLE incident and prevalent cases were most common in North-West China and less common in southern and eastern China. Distinct variations in incidence rates across different regions are also consistent with the varying levels of ultraviolet radiation exposure in China. Additionally, the average estimated annual per-capita cost was 1599.34 US dollars in SLE patients, with the highest costs observed in adolescent and young adult patients among different age groups. The SLE population in China is rapidly expanding, and younger at onset, especially in women, which has placed significant burdens on China's healthcare system.

Protein kinase MeSnRK2.3 positively regulates starch biosynthesis by interacting with the transcription factor MebHLH68 in cassava.

Starch biosynthesis involves numerous enzymes and is a crucial metabolic activity in plant storage organs. Sucrose non-fermenting related protein kinase 2 (SnRK2) is an abscisic acid (ABA)-dependent kinase and a significant regulatory enzyme in the ABA signaling pathway. However, whether SnRK2 kinases regulate starch biosynthesis is unclear. In this study, we identified that MeSnRK2.3, an ABA-dependent kinase, was highly expressed in the storage roots of cassava and was induced by ABA. Overexpression of MeSnRK2.3 in cassava significantly increased the starch content in the storage roots and promoted plant growth. MeSnRK2.3 was further found to interact with the cassava basic helix-loop-helix 68 (MebHLH68) transcription factor in vivo and in vitro. MebHLH68 directly bound to the promoters of sucrose synthase 1 (MeSUS1), granule-bound starch synthase I a (MeGBSSIa), and starch-branching enzyme 2.4 (MeSBE2.4), thereby upregulating their transcriptional activities. Additionally, MebHLH68 negatively regulated the transcriptional activity of sucrose phosphate synthase B (MeSPSB). Moreover, phosphorylated MebHLH68 by MeSnRK2.3 up-regulated the transcription activity of MeSBE2.4. These findings demonstrated that the MeSnRK2.3-MebHLH68 module connects the ABA signaling pathway and starch biosynthesis in cassava, thereby providing direct evidence of ABA-mediated participation in the sucrose metabolism and starch biosynthesis pathway.

Prevalence and clinical significance of anti-SSA antibody in the Chinese health screening population.

Anti-SSA antibodies are non-organ-specific autoantibodies highly prevalent in various autoimmune diseases. This study primarily investigated the prevalence of anti-SSA antibodies in the health screening population. Additionally, we explored the clinical features of the anti-SSA antibody-positive population and evaluated the development of connective tissue diseases (CTD) over the years in individuals with anti-SSA antibodies for whom follow-up was available. 64045 individuals without a history of CTD from 2013 to 2022 who visited Peking Union Medical College Hospital for health screening were screened for autoimmune antibodies. 1.7% (1091/64045) of the Chinese health screening population were positive for anti-SSA antibodies, with a prevalence of 0.9% (290/33829) in men and 2.7% (801/30216) in women. Compared with matched autoantibody-negative controls, anti-SSA antibody-positive individuals had higher levels of serological abnormalities including erythrocyte sedimentation rate (ESR) [10 (6-15) mm/h vs. 7 (4-12) mm/h, p<0.0001], rheumatoid factor (RF) [7.15 (4.30-16.90) IU/ml vs. 5.00 (3.20-7.90) IU/ml, p<0.0001], and Immunoglobulin G [13.09 (11.20-15.45) g/L vs. 11.34 (9.85-13.18) g/L, p<0.0001], and lower levels of white blood cells (WBC) (5.49 ± 1.50 *109/L vs. 5.82 ± 1.49 *109/L, p<0.0001). Additionally, they had a higher proportion of coexisting thyroid autoantibodies, including anti-thyroid peroxidase antibodies (TPO-Ab) (17.1% vs. 11.3%, p<0.0001) and anti-thyroglobulin antibodies (Tg-Ab) (17.8% vs. 11.0%, p<0.0001). Among the 381 subjects who were anti-SSA positive and followed up for a median of 4.6 years, 146 (38.3%) individuals developed CTD, including 68 (17.8%) cases of primary Sjögren syndrome (pSS), 10 (2.6%) cases of rheumatoid arthritis (RA), 5 cases (1.3%) of systemic lupus erythematosus (SLE), and 59 (15.5%) cases of undifferentiated connective tissue disease (UCTD). 235 (61.7%) individuals did not develop CTD over a median time of 5.9 (2.9-8.1) years after the earliest autoantibody detection. Elevated ESR (>20 mm/h), RF positivity (>20 IU/ml), and female gender were identified as independent risk factors for CTD among the anti-SSAantibody-positive individuals. Anti-SSA antibodies were found in 17 among approximately 1000 individuals without a history of autoimmune diseases. Anti-SSA antibody-positive individuals are advised to periodically monitor thyroid function. Elevated ESR (>20 mm/h), female gender, and rheumatoid factor positivity may delineate a high-risk cohort for CTDs.

Predictive Factors for the Common Adverse Maternal and Fetal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus.

Objectives: This study aimed to evaluate the outcomes of pregnancy in patients with systemic lupus erythematosus (SLE). It focused on identifying clinical and laboratory markers that could predict the common adverse pregnancy outcomes (APOs) after 20 weeks of gestation, namely preeclampsia (PE) and preterm birth (PTB) in them. Methods: Pregnant SLE women who delivered at the study center from 2010 to 2023 were retrospectively analyzed. Categorical variables were evaluated using the chi-square test or Fisher's exact test, while continuous variables underwent Mann-Whitney U testing. Stepwise regression was used to assess the predictors of pregnancy outcomes. Results: The study enrolled 445 pregnancies in 408 women diagnosed with SLE. Of these, 202 pregnancies (45.4%) resulted in at least one APO. Disease flare-ups, hypertension, and proteinuria during the first trimester were primary predictors of at least one APO and PTB. The most frequently recorded maternal adverse outcome was PE (14.6%), while PTB accounted for 32.6% of fetal adverse outcomes. Multivariate regression analysis identified hypertension, history of PE, associated antiphospholipid syndrome (APS), proteinuria, and low serum C4 in the first trimester as independent risk factors for PE. Regular follow-ups at our center correlated with lower risks of APOs, PE, and PTB. APS also emerged as a risk factor for PTB, whereas the use of hydroxychloroquine (HCQ) during pregnancy seemed to protect against PTB. Conclusion: For pregnancies complicated by SLE, we recommend early pregnancy screening for proteinuria-even in the absence of lupus nephritis-as well as continued use of HCQ and routine prenatal care throughout pregnancy.

Single-cell RNA sequencing of peripheral blood mononuclear cells from pregnant women with Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), an autoimmune condition, presents pregnancy-related risks, impacting maternal and fetal health. The immune cell composition and gene expression profiles in pregnant SLE patients, as well as the molecular mechanisms of active SLE patients during pregnancy, remain unclear. In our study, we enrolled 12 patients: three active SLE individuals (SLE-AT group, SLEDAI > 12, non-pregnant women), three inactive SLE individuals (SLE-NP group, SLEDAI ranging 0 to 6, non-pregnant women), three pregnant women with active SLE (SLE-C group, SLEDAI > 12), and three pregnant women with inactive SLE (SLE-NC group, SLEDAI range 0 to 6 score). Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) was conducted using the 10x Genomics technique. We observed upregulation of genes like CCDC15 and TRBV4-2 in T cells and CMPK2, IFIT1, and OAS2 in monocytes in the SLE-C group. Notably, gene sets related to Cell Cycle and IFN Response showed significant differences between the SLE-C and SLE-NC groups in naïve CD8 T cells. Our comparison of immune cell type ratios and transcriptional patterns between active and inactive SLE during pregnancy sheds light on the single-cell level changes in SLE status during pregnancy, offering insights for future SLE prediction and treatment strategies.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Furthermore, SLE women have an increased likelihood of encountering adverse pregnancy outcomes such as diabetes and hypertension. The etiology of SLE involves a multifaceted interplay of genetic, immune, endocrine, and environmental factors, which contributes to a breakdown in the immune system's tolerance to self-antigens. Recent studies have highlighted a strong correlation between the severity of renal involvement in lupus nephritis and B cell dysfunction in patients, as elucidated through single-cell transcriptomics. Additionally, comparative studies have revealed notable differences in the immune cell profile between pregnant women with lupus and healthy pregnant women. A key observation the marked reduction in the proportion of CD4+ T cells in pregnant women suffering from lupus. Despite these findings, the detailed transcriptomic alterations within high-resolution immune cell profiling during activate phase of SLE in pregnancy remain inadequately understood. In our study, we focused on comparing the transcriptomic expression patterns of peripheral blood immune cells between pregnant women with active SLE and those with stable SLE. Our data confirmed significant differences in IFN signaling and pregnancy-related factors in T cells, NK cells, B cells, and macrophages, contrasting the immune cells of pregnant women with active SLE against those with stable SLE. Additionally, the proportion of CD56+ NK cells was significantly increased in pregnant women with SLE. The correlation between the transcriptomic profiles of immune cells and the activity of SLE during pregnancy may provide potential strategies for predicting and treating SLE during pregnancy.

Impact of antiphospholipid antibodies on cardiac valve lesions in systemic lupus erythematosus: a systematic review and meta-analysis.

This meta-analysis assesses antiphospholipid antibodies' (aPLs) impact on heart valve disease in Systemic Lupus Erythematosus (SLE) patients. We searched PubMed, Embase, Cochrane, and Web of Science up to January 2024 for comparative studies of heart valve disease in aPL-positive versus aPL-negative SLE patients. Fixed-effect or random-effect models were used to synthesize data, with I2 and sensitivity analyses for heterogeneity and the trim-and-fill method for publication bias. Including 25 studies with 8089 patients, of which 919 had valvular changes, aPLs significantly increased the risk of heart valve disease (OR = 2.24, 95% CI: 1.58-3.18, p < 0.001). Lupus anticoagulant (LA) indicated the highest risk (OR = 4.90, 95% CI: 2.26-10.60, p < 0.001), anticardiolipin antibodies (aCL) doubled the risk (OR = 2.69, 95% CI: 1.47-4.93, p = 0.001), and anti-ß2 glycoprotein I (aß2GPI) showed a 70% increase (OR = 1.70, 95% CI: 1.17-2.45, p = 0.005). Valve-specific analysis indicated the mitral valve was most commonly involved (26.89%), with higher occurrences in aPL-positive patients (33.34% vs. 15.92%, p = 0.053). Aortic and tricuspid valve involvements were 13.11% vs. 5.42% (p = 0.147) and 12.03% vs. 8.52% (p = 0.039), respectively. Pulmonary valve disease was rare and similar across groups (1.01% in aPL-positive vs. 1.52% in aPL-negative). Significantly, only tricuspid valve disease showed increased risk in aPL-positive patients (OR = 2.66, 95% CI: 1.05-6.75, p = 0.039). APLs notably increase the risk of heart valve disease in SLE patients, with a pronounced effect on tricuspid valve involvement. Regular cardiac assessments for aPL-positive SLE patients are crucial for timely intervention and improved prognosis.

Coronary periarteritis and pericarditis are rare but distinct manifestations of heart involvement in IgG4-related disease: a retrospective cohort study.

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

Depletion-assisted multiplexed cell-free RNA sequencing reveals distinct human and microbial signatures in plasma versus extracellular vesicles.

BACKGROUND: Cell-free long RNAs in human plasma and extracellular vesicles (EVs) have shown promise as biomarkers in liquid biopsy, despite their fragmented nature. METHODS: To investigate these fragmented cell-free RNAs (cfRNAs), we developed a cost-effective cfRNA sequencing method called DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing). DETECTOR-seq utilised a meticulously tailored set of customised guide RNAs to remove large amounts of unwanted RNAs (i.e., fragmented ribosomal and mitochondrial RNAs) in human plasma. Early barcoding strategy was implemented to reduce costs and minimise plasma requirements. RESULTS: Using DETECTOR-seq, we conducted a comprehensive analysis of cell-free transcriptomes in both whole human plasma and EVs. Our analysis revealed discernible distributions of RNA types in plasma and EVs. Plasma exhibited pronounced enrichment in structured circular RNAs, tRNAs, Y RNAs and viral RNAs, while EVs showed enrichment in messenger RNAs (mRNAs) and signal recognition particle RNAs (srpRNAs). Functional pathway analysis highlighted RNA splicing-related ribonucleoproteins (RNPs) and antimicrobial humoral response genes in plasma, while EVs demonstrated enrichment in transcriptional activity, cell migration and antigen receptor-mediated immune signals. Our study indicates the comparable potential of cfRNAs from whole plasma and EVs in distinguishing cancer patients (i.e., colorectal and lung cancer) from healthy donors. And microbial cfRNAs in plasma showed potential in classifying specific cancer types. CONCLUSIONS: Our comprehensive analysis of total and EV cfRNAs in paired plasma samples provides valuable insights for determining the need for EV purification in cfRNA-based studies. We envision the cost effectiveness and efficiency of DETECTOR-seq will empower transcriptome-wide investigations in the fields of cfRNAs and liquid biopsy. KEYPOINTS: DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing) enabled efficient and specific depletion of sequences derived from fragmented ribosomal and mitochondrial RNAs in plasma. Distinct human and microbial cell-free RNA (cfRNA) signatures in whole Plasma versus extracellular vesicles (EVs) were revealed. Both Plasma and EV cfRNAs were capable of distinguishing cancer patients from normal individuals, while microbial RNAs in Plasma cfRNAs enabled better classification of cancer types than EV cfRNAs.

Transcriptomics Identifies Differentially Expressed Genes Inducing Tuber Formation in Early- and Late-Maturing Potatoes.

The timing of potato tuberization is affected by potato ripeness, environmental factors, and polygene regulation. The accurate control of the transition to tuberization has both scientific and practical production value, but the key factors regulating this transition remain unclear. This study grafted an early-maturing potato variety (Favorita) scion to the late-maturing Qingshu 9 variety and demonstrated that a heterologous early-maturing scion can induce early potato formation on a late-maturing rootstock. The transcriptome of functional leaves and stolons of grafted plants was comprehensively analyzed and 593 differentially expressed genes (DEGs) were identified, including 38 transcription factors. Based on gene molecular function analysis and previous reports, we propose that PIF5, bHLH93, CBF3, ERF109, TCP19, and YABBY1 are the key DEGs that induce tuber formation in early- and late-maturing potatoes. The YABBY1 gene was subjected to functional verification. The leaf area of StYABBY1-overexpressing plants was smaller than the wild type and no potato tubercles were formed, while an RNA interference plant line showed no change in leaf area and formed tubers, indicating that StYABBY1 has a role in leaf size regulation and tuber formation.

Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.

BACKGROUND: Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. METHODS: SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. FINDINGS: Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79). CONCLUSION: This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. FUNDING: This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

Immunometabolic alteration of CD4+ T cells in the pathogenesis of primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a prevalent autoimmune disorder wherein CD4+ T cells play a pivotal role in its pathogenesis. However, the underlying mechanisms driving the hyperactivity of CD4+ T cells in pSS remain poorly understood. This study aimed to investigate the potential role of immunometabolic alterations in driving the hyperactivity of CD4+ T cells in pSS. We employed Seahorse XF assay to evaluate the metabolic phenotype of CD4+ T cells, conducted flow cytometry to assess the effector function and differentiation of CD4+ T cells and measured the level of intracellular reactive oxygen species (ROS). Additionally, transcriptome sequencing, PCR, and Western blotting were utilized to examine the expression of glycolytic genes. Our investigation revealed that activated CD4+ T cells from pSS patients exhibited elevated aerobic glycolysis, rather than oxidative phosphorylation, resulting in excessive production of IFN-γ and IL-17A. Inhibition of glycolysis by 2-Deoxy-D-glucose reduced the expression of IFN-γ and IL-17A in activated CD4+ T cells and mitigated the differentiation of Th1 and Th17 cells. Furthermore, the expression of glycolytic genes, including CD3E, CD28, PIK3CA, AKT1, mTOR, MYC, LDHA, PFKL, PFKFB3, and PFKFB4, was upregulated in activated CD4+ T cells from pSS patients. Specifically, the expression and activity of LDHA were enhanced, contributing to an increased level of intracellular ROS. Targeting LDHA with FX-11 or inhibiting ROS with N-acetyl-cysteine had a similar effect on reversing the dysfunction of activated CD4+ T cells from pSS patients. Our study unveils heightened aerobic glycolysis in activated CD4+ T cells from pSS patients, and inhibition of glycolysis or its metabolite normalizes the dysfunction of activated CD4+ T cells. These findings suggest that aerobic glycolysis may be a promising therapeutic target for the treatment of pSS.

Exploring the impact of acute viral exposure on clinical characteristics and antibody profiles in antiphospholipid syndrome: a study in CAPSTONE.

The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-ß-2-glycoprotein I-IgG (aß2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aß2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aß2GP1-IgG, aß2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.