Lupus Research Articles

The balance between conventional and unconventional T follicular helper cells influences autoreactive B cell responses.

The balance between conventional and unconventional T follicular helper cells influences autoreactive B cell responses.

Coexistence of antinucleosome and anti-double-stranded DNA antibodies is associated with severe systemic lupus erythematosus in Tunisian patients.

We sought to compare clinical features among distinct antibody profiles defined by the presence or absence of antinucleosome (anti-NCS) and anti-double-stranded DNA (anti-dsDNA) antibodies in Tunisian patients with systemic lupus erythematosus (SLE). The study enrolled 131 patients with SLE meeting at least 4 American College of Rheumatology or SLICC criteria. Participants were recruited from the Department of Internal Medicine and Rheumatology at the university teaching hospital of Monastir between January 2000 and December 2022. The patients were divided into 4 groups: Group 1 with neither anti-dsDNA nor anti-NCS; Group 2 with anti-dsDNA and no anti-NCS; Group 3 with anti-NCS lacking anti-dsDNA; and Group 4 with both anti-NCS and anti-dsDNA. The mean (SD) age at the time of diagnosis for the 131 participants with SLE was 38.7 (15.1) years; the ratio of female to male individuals was 7.2. Thirty-four (26%) patients were positive for anti-NCS and anti-dsDNA (group 4: antinuclear antibody pattern AC-1, 72%; pattern AC-5, 16%), and 30 (22.9%) were positive for anti-NCS and negative for anti-dsDNA (group3: pattern AC-1, 53.6%; pattern AC-5, 32.1%). The group 3 patients showed higher peripheral neuropsychiatric SLE (P =.034) and lower rates of disease activity (P =.01). The comparison between the 4 groups showed that group 4 patients had the highest frequency of lupus nephritis (P ≤.001) and the highest rate disease activity (P =.013). Patients with both anti-NCS and anti-dsDNA at the time of diagnosis are likely to have severe SLE, while anti-NCS was associated with nonsevere disease in patients with SLE who lack anti-dsDNA.

Unsupervised machine learning identifies distinct systemic lupus erythematosus patient endotypes with differential response to belimumab.

To determine systemic lupus erythematosus (SLE) endotypes according to B cell immunophenotyping and serological profile and assess endotypes' response to belimumab. We analysed data from 796 patients with SLE from the phase III trial BLISS-SC. Unsupervised machine learning employing factor analysis of mixed data (FAMD) and subsequent clustering determined endotypes based on B cell immunophenotyping and serological profiles. Cox regression was used to assess belimumab efficacy on inducing lupus low disease activity state (LLDAS) and Definitions of Remission in SLE (DORIS) remission within clusters. Three endotypes were determined. Compared to each other, cluster 1 (n = 191) displayed higher proportions of CD19+CD24b+CD27+ regulatory B cells [mean ± standard deviation (SD): 35.9%±12.6%], CD19+CD20+CD27+ bulk memory B cells (32.2%±9.9%), CD19+CD20+CD69+ activated B cells (0.2%±0.3%), CD19+CD20-CD138+ long-lived plasma cells (0.7%±1.0%), and CD19+CD38b+CD27b+ SLE-associated plasma cells (6.6%±7.0%). Cluster 2 (n = 366) displayed higher proportions of CD19+CD24bbrightCD38bbrightCD27- transitional B cells (6.3%±9.0%) and CD19+CD20+CD27- naïve B cells (85.4%±7.2%), and lower proportions of CD19+CD20-CD138+ peripheral long-lived plasma cells (0.2%±0.3%) and CD19+CD38b+CD27b+ SLE-associated plasma cells (1.6%±2.0%). Cluster 3 (n = 239) displayed a higher proportion of CD19+CD20+CD138+ short-lived plasma cells (0.1%±0.1%) and higher serological activity, being enriched in anti-double stranded(ds)DNA, anti-extractable nuclear antigens (ENA), antiphospholipid antibodies, and hypocomplementemia. Use of belimumab was superior to placebo in inducing sustained LLDAS (HR: 2.22; 95% CI: 1.18-4.17; p = 0.014) and DORIS remission (HR: 3.45; 95% CI: 1.2-9.94; p = 0.022) in cluster 2. Three distinct SLE endotypes were identified based on B cell immunophenotyping and serological profiles, showing differential benefit from belimumab therapy.

Immune cells in systemic lupus erythematosus: biology and traditional Chinese medicine therapy.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by a progressive breakdown of immune tolerance to self-antigens, resulting in multiple tissue damage and clinical symptoms. Innate and adaptive immune cells including dendritic cells, macrophages, myeloid-derived suppressor cells (MDSCs), T cells and B cells are the key drivers in perpetuating and amplifying of this systemic disease. In this review we offer a comprehensive overview of recent advances in understanding the immune-pathogenesis of SLE with particular emphasis on regulatory immune cells exhibiting immunosuppressive properties, as well as newly identified factors influencing immune cell function and lineage differentiation. Furthermore, we discuss traditional Chinese medicine and natural extracts that have shown therapeutic effects on SLE by modulating immune cell differentiation and function, which may provide insights into their clinical applications.

The potential crosstalk genes and molecular mechanisms between systemic lupus erythematosus and periodontitis

BackgroundSeveral studies have demonstrated an increased risk of periodontitis (PD) among patients diagnosed with systemic lupus erythematosus (SLE). However, the underlying common mechanism between them remains incompletely understood. Accordingly, the aim of this study is to examine diagnostic biomarkers and potential therapeutic targets for SLE and PD by leveraging publicly accessible microarray datasets and transcriptome analysis.MethodDatasets pertaining to SLE and PD were retrieved from the Gene Expression Omnibus (GEO) database, and subsequently analyzed for differentially expressed genes (DEGs). Key gene modules were identified through weighted gene co-expression network analysis (WGCNA), and shared genes were obtained by overlapping key genes between DEGs and WGCNA. These shared genes were subsequently subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, leading to the establishment of a Protein-Protein Interaction (PPI) network. Random forest (RF) and Least Absolute Shrinkage and Selection Operator (Lasso) regression were employed to identify key hub genes. Receiver operating characteristic (ROC) curves were generated using a new validation dataset to evaluate the performance of candidate genes. Finally, levels of immune cell infiltration in SLE and PD were assessed using CIBERSORTx.ResultsA total of 50 core genes were identified between the genes screened by WGCNA and DEGs. Functional enrichment analysis revealed that these genes are primarily associated with the PI3K-Akt and B-cell receptor signaling pathways. Additionally, using machine learning algorithms and ROC curve analysis, a total of 8 key genes (PLEKHA1, CEACAM1, TNFAIP6, TCN2, GLDC, GNG7, LY96, VCAN) were identified Finally, immune infiltration analysis highlighted the significant roles of neutrophils, monocytes, plasma cells, and gammadelta T cells (γδ T cells) in the pathogenesis of both SLE and PD.ConclusionThis study identifies 8 hub genes that could potentially serve as diagnostic markers for both SLE and PD, highlighting the importance of VCAN and LY96 in diagnosis. Moreover, the involvement of the PI3K-Akt signaling pathway in both diseases suggests its significant role. These identified key genes and signaling pathways lay the groundwork for deeper comprehension of the interplay between SLE and PD.

Baby you can drive my CAR-T cells.

ObjectiveTo evaluate the potential of chimeric antigen receptor T-cell (CAR-T) therapy in revolutionizing the treatment of systemic lupus erythematosus (SLE) and to outline necessary future steps for its implementation.MethodsA careful literature search was conducted for relevant English language papers on pubmed.ResultsPreliminary data suggest that CAR-T therapy could significantly improve SLE outcomes. Demonstrating remarkable clinical and serologic improvements in SLE patients, with all treated patients achieving remission and discontinuing conventional steroids and immunosuppressive drugs. To realize this potential, it is imperative to advance our understanding and application of CAR-T therapy. Rigorous research is necessary to validate current findings, and clinical trials must be conducted to assess both the short- and long-term efficacy and safety across diverse populations. Identifying appropriate patient populations is crucial, as CAR-T may also address compliance issues. Despite its current high cost, the financial burden is comparable to the long-term costs of severe SLE treatment. Strategies to reduce costs, including production efficiencies and outpatient treatment options, are under exploration. Early intervention could enhance its feasibility and impact on long-term prognosis.ConclusionCAR-T therapy holds promise for altering the prognosis of SLE and potentially offering a cure. However, substantial efforts are required to validate its efficacy, ensure safety, identify suitable patient cohorts, and reduce financial barriers. This development represents an exciting advancement in SLE treatment, necessitating urgent and focused research and clinical application.

Osteopontin in Chronic Inflammatory Diseases: Mechanisms, Biomarker Potential, and Therapeutic Strategies

Chronic inflammatory diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), atherosclerosis, and inflammatory bowel disease (IBD), pose major global health concerns. These disorders are marked by persistent inflammation, immune system dysfunction, tissue injury, and fibrosis, ultimately leading to severe organ dysfunction and diminished quality of life. Osteopontin (OPN), a multifunctional extracellular matrix protein, plays a crucial role in immune regulation, inflammation, and tissue remodeling. It promotes immune cell recruitment, stimulates pro-inflammatory cytokine production, and contributes to fibrosis through interactions with integrins and CD44 receptors. Additionally, OPN activates key inflammatory pathways, including NF-κB, MAPK, and PI3K/Akt, further aggravating tissue damage in chronic inflammatory conditions. Our review highlights the role of OPN in chronic inflammation, its potential as a biomarker, and its therapeutic implications. We explore promising preclinical approaches, such as monoclonal antibodies, small molecule inhibitors, and natural compounds like curcumin, which have demonstrated potential in mitigating OPN-driven inflammation. However, challenges persist in selectively targeting OPN while maintaining its essential physiological roles, including bone remodeling and wound healing. Our review offers insights into therapeutic strategies and future research directions.

COVID-19 vaccine hesitancy among parents of children with systemic lupus erythematosus: a comment.

COVID-19 vaccine hesitancy among parents of children with systemic lupus erythematosus: a comment.

Hydroxychloroquine dose-dependently reduces the risk of incident diabetes in primary Sjögren syndrome patients on glucocorticoids: a nationwide population-based cohort study

BackgroundHydroxychloroquine (HCQ) is commonly used to treat Sjögren syndrome (SS). Glucocorticoids, which are commonly applied for managing primary SS (pSS), can disrupt glucose metabolism and increase diabetes mellitus (DM) risk. HCQ reduces DM risk in systemic lupus erythematosus and rheumatoid arthritis.ObjectiveThis study aimed to investigate the relationship between HCQ and glucocorticoids in the incidence of new-onset diabetes in pSS.MethodsThis nationwide population-based cohort study identified patients diagnosed with pSS from the Taiwan’s National Health Insurance Research Database from 2006 to 2015. Multivariate and stratified analyses, Kaplan–Meier method, and Cox proportional hazard regression were used to evaluate DM risk associated with the use of HCQ and glucocorticoid, both individually and in combination.ResultsAmong pSS patients (4,874 HCQ users and 2,437 HCQ nonusers), 497 patients developed DM over an average follow-up of 4.89 years. Multivariate analysis revealed significantly lower adjusted hazard ratios (aHRs) for DM in HCQ users in the 151–350 cumulative defined daily dose (cDDD) and ≥ 351 cDDD subgroups (0.600, 95% CI: 0.454–0.794 and 0.326, 95% CI: 0.246–0.433, respectively) compared with HCQ nonusers. High-dose glucocorticoids (≥ 151 cDDD) were linked to increased DM risk (aHR: 1.833, 95% CI: 1.410–2.383). However, high-dose HCQ (> 350 cDDD) mitigated this risk, even the risk caused by the use of high-dose glucocorticoids (≥ 151 cDDD) (aHR: 0.632, 95% CI: 0.421–0.948, P < 0.01).ConclusionsOur study demonstrated that HCQ exposure significantly reduces the risk of developing diabetes in patients with pSS. While higher doses of glucocorticoids are associated with an increased diabetes risk, concurrent HCQ use mitigates this risk in a dose-dependent manner.

HMGB1: new biomarker and therapeutic target of autoimmune and autoinflammatory skin diseases

High-mobility group box 1 (HMGB1) is expressed in almost all human cells. During cell activation and cell death, the nucleoprotein HMGB1 can translocate to the extracellular space, thus mediating the early inflammatory response as an alarmin or damage-associated molecular pattern (DAMP). Extracellular HMGB1 interacts with immune cells by binding to pattern recognition Toll-like receptors (TLRs), including TLR2 and TLR4, and the receptor for advanced glycation end products (RAGE), thus mediating the immune response to protect the host against pathogens and maintain immune balance. HMGB1 is reportedly upregulated and is a critical biomarker for monitoring disease activity in several chronic inflammatory or autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus and vitiligo. Additionally, the inhibition of HMGB1 expression or its activity has beneficial effects on disease activity in animal models of autoimmune diseases. Thus, HMGB1 is an indispensable biomarker and an important therapeutic target for autoimmune diseases. This review provides a detailed summary of the biological function of HMGB1 and provides a comprehensive outlook in terms of HMGB-focused diagnostic and therapeutic applications in autoimmune skin diseases.

Treatment and clinical outcomes of pediatric autoimmune hemolytic anemia: real-world single-center data from Korea.

: Autoimmune hemolytic anemia (AIHA) is rare and characterized by hemolytic anemia with a positive direct antiglobulin test result after the exclusion of other causes. While adults often relapse within 1 year of first-line steroid therapy, children generally respond well. However, current treatment approaches lack substantial evidence and are primarily expert opinion-based. : This study aimed to contribute our single-center experience to pediatric AIHA treatment guidelines. : Between January 2012 and June 2024, 475 children were diagnosed with anemia; of them, 18 had immune hemolytic anemia, including six with neonatal alloimmune hemolytic anemia, two who were treated at other centers, and two with transient bone marrow suppression due to a viral infection. Thus, this study retrospectively analyzed the treatment responses of eight patients with AIHA. : The median age at diagnosis was 5.2 (range, 2.3-11.8) years; 62.5% (5/8) were male. Median hemoglobin (Hb) at diagnosis was 6.3 (range, 3.4-9.5) g/dL, median reticulocyte index was 6.53% (range, 1.64-22.07%), median total bilirubin was 2.75 (range, 0.98-7.23) mg/dL, and median lactate dehydrogenase was 1662.0 (range, 790-2921) U/L. All haptoglobin levels were <10 mg/dL. Treatments included steroids (8/8), red blood cell transfusions (5/8), and intravenous immunoglobulins (2/8). Half of the steroid-treated patients received intravenous methylprednisolone for 1-5 days, while half received oral prednisolone (median, 1.78 [range, 0.79-3.39] mg/kg/day). The median time to age-adjusted normal Hb levels was 16.5 (range, 9-22) days. Steroids were administered for a median 37.5 (range, 14-119) days. Excluding one patient later diagnosed with systemic lupus erythematosus, no relapses occurred during the 3-19-month follow-up period. : Patients with pediatric AIHA showed relapse-free rapid hematological improvement and sustained steroid responses within 2 months, suggesting that systematic steroid treatment is feasible and highlighting the need for multicenter trials to establish standardized guidelines.

Recent research progress on the association between cell death and the pathogenesis of childhood-onset systemic lupus erythematosus

Recent research progress on the association between cell death and the pathogenesis of childhood-onset systemic lupus erythematosus

Coexisting systemic lupus erythematosus with lupus nephritis and sickle cell trait: a case report of rare combination

Coexisting systemic lupus erythematosus with lupus nephritis and sickle cell trait: a case report of rare combination

Association between Neutrophil-Lymphocyte Ratio and Preeclampsia: A Case-Control Study

Background &amp; objective: Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and multiorgan dysfunction, affecting 2-8% of pregnancies and posing significant risks for maternal and fetal health. This study investigates the association between the neutrophil-lymphocyte ratio (NLR) and preeclampsia, aiming to explore NLR's potential as a cost-effective biomarker for early diagnosis. Methods: This cross-sectional study was conducted at Sir Salimullah Medical College Mitford Hospital, Dhaka, over 12 a period of months The study included a total of 78 singleton pregnant women, aged 18 to 35, and between 28 to 40 weeks of gestation. While the case group consisted of 26 women diagnosed with preeclampsia, the control group formed of 52 healthy pregnant women. Pregnant women with known comorbidities, including diabetes, hypertension, hypothyroidism, systemic lupus erythematosus (SLE), or any maternal infections (e.g., respiratory tract infections, urinary tract infections) were excluded from the study. Results: More than 40% of women with preeclampsia were aged 25 to 30 years, while nearly half of the control group were aged 18 to 25. No significant age difference was found between groups (27.3 ± 5.3 vs. 35.8 ± 3.3, p = 0.184). The case group exhibited significantly higher absolute neutrophil counts (6.83 ± 1.39 vs. 5.56 ± 1.19 ×10^9/L, p &lt; 0.001) and NLR (3.7 ± 0.4 vs. 3.0 ± 0.6, p &lt; 0.001) compared to controls. Significant positive correlations were observed between NLR and both systolic (r = 0.490, p &lt; 0.001) and diastolic blood pressures (r = 0.587, p &lt; 0.001). Conclusion: Our findings suggest that elevated NLR is associated with preeclampsia and may serve as a valuable biomarker for its diagnosis. The study highlights the importance of NLR in enhancing early detection and management of preeclampsia, particularly in resource-limited settings. Ibrahim Card Med J 2024; 14(1): 35-39

Assessment of myocardial dysfunction of patients with systemic lupus erythematosus based on myocardial perfusion imaging and analysis of potential influencing factors.

The incidence and prevalence of systemic lupus erythematosus (SLE) have increased annually over the past decade. The involvement of myocardium is one of the main reasons for the poor prognosis of patients with SLE. Identifying myocardial involvement in patients with autoimmune diseases and providing early targeted treatment can improve patient outcomes. The aim of this study is to evaluate myocardial dysfunction in patients with SLE using 99mTc-MIBI rest gated myocardial perfusion imaging (rGMPI) and to investigate factors associated with myocardial dysfunction. 76 patients with SLE were prospectively enrolled in the study and 46 patients without autoimmune diseases or other inflammatory diseases who had undergone 99mTc-MIBI rGMPI were selected as a control group. Results of relevant blood test indicators, echocardiography and rGMPI were recorded, and comparison was made between the two groups. Meanwhile, based on diagnostic results of rGMPI, SLE patients were divided into myocardial dysfunction group and normal myocardial function group and to analyze the influencing factors of myocardial dysfunction in SLE patients. The incidence of myocardial dysfunction was significantly higher in SLE patients than in controls (30.3% vs 0%, 2= 16.131, p < .001). Moderate/severe disease activity, decreased myocardial perfusion and positive anti-SSA/Ro52kDa antibody were associated with impaired myocardial function in SLE patients (OR = 2.753, 5.359, 3.646; p = .049, 0.015, 0.014). Positive anti-SSA/Ro52kDa antibody was is independently correlated with myocardial dysfunction in SLE patients [OR (95% CI) = 3.159 (1.071-9.316), p = .037]. In conclusion, 99mTc-MIBI rGMPI can noninvasively evaluate myocardial dysfunction in patients with SLE and provide evidence for clinical treatment decisions. Positive anti-SSA/Ro52kDa antibody was an independent risk factor for myocardial dysfunction in SLE patients.

Haemophagocytic lymphohistiocytosis as an initial presentation of undiagnosed systemic lupus erythematosus

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal hyperinflammatory syndrome with multi-organ involvement. It may occur secondary to autoimmune diseases such as systemic lupus erythematosus (SLE). Case description: This report describes an unusual case of a previously healthy 29-year-old female medical student who presented with a one-month history of recurrent fever, fatigue and significant weight loss. Initial laboratory investigations revealed pancytopaenia, hyperferritinaemia and hypertriglyceridaemia. Infectious disease workup was negative. Serological testing demonstrated positive antinuclear antibody and anti-double-stranded DNA antibodies, while bone marrow biopsy confirmed haemophagocytosis. The patient was diagnosed with secondary HLH due to SLE. During treatment in the intensive care unit, the patient developed psychosis manifested by visual hallucinations and mood swings. A diagnosis of neuropsychiatric SLE was confirmed by exclusion of other causes (e.g. steroid therapy) and the presence of non-specific white matter hyperintensities on brain magnetic resonance imaging. Combination therapy with high-dose corticosteroids, intravenous immunoglobulin and rituximab resulted in significant clinical and laboratory improvements within two weeks. Conclusion: This case illustrates how HLH can be the initial manifestation of previously undiagnosed SLE. Hence, clinicians should maintain a high index of suspicion for underlying autoimmune disorders such as SLE when evaluating patients with HLH, as early recognition and appropriate immunosuppressive therapy are crucial for optimal outcomes.

Association of regional adiposity distribution with risk of autoimmune diseases.

To detect the association between regional adiposity distribution and the incidence of seven autoimmune diseases (ADs) in UK Biobank cohort and Mendelian randomization (MR) analyses. We used Cox models to evaluate the associations between seven adiposity distribution measures and seven ADs (systemic lupus erythematosus [SLE], seropositive rheumatoid arthritis [PRA], psoriasis [PSO], multiple sclerosis [MS], myasthenia gravis [MG], Crohn's disease [CD] and ulcerative colitis [UC]) in cohort studies. In the MR analyses, we used the inverse variance-weighted MR method to estimate causal effects between adiposity distribution and obesity-related ADs in the cohort. In the cohort study, PSO, MG, CD, and female UC were associated with almost all types of adiposity distribution; PRA and male UC were associated with central adiposity distribution; SLE and MS were found to be not associated with any types of obesity. Almost all adiposity distribution were certified in MR as an exposure to PSO, MG and PRA. Adiposity, despite its distribution, are associated with an increased risk of PSO and MG, and central adiposity distribution is robustly associated with the increased risk of PRA, indicating that lifestyle interventions aimed at obesity contribute to preventing ADs. Key Points • Body mass index (BMI) was a risk factor for several autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis (PSO), multiple sclerosis (MS) and inflammatory bowel disease (IBD). However, obesity as a heterogeneous and complex condition and that regional fat mass has obviously differential contributions to the development of obesity-related diseases. • We revealed that all types of adiposity distribution, whether general, central or peripheral, were associated with an increased risk of psoriasis and myasthenia gravis, and central adiposity distribution was robustly associated with the increased risk of seropositive rheumatoid arthritis. • Our findings indicated that lifestyle interventions aimed at individuals with obesity might contribute to preventing autoimmune diseases.

Causal effect of three autoimmune diseases on brain functional networks and cerebrospinal fluid metabolites to underlie the pathogenesis of autoimmune psychosis: a two-sample mendelian randomization analysis

BackgroundAutoimmune diseases such as Systemic Lupus Erythematosus (SLE), Sjögren’s Syndrome (SS), and Hashimoto’s Thyroiditis (HT) frequently exhibit neuropsychiatric manifestations, including cognitive impairment, depression, anxiety, and so on, yet the exact pathogenesis underlying this association remain incompletely understood. Dysfunction of brain resting-state functional networks and cerebrospinal fluid (CSF) metabolite disturbances have been widely reported in psychiatric disorders. However, the application of resting-state functional magnetic resonance imaging (rsfMRI) and CSF metabolomics in the diagnosis and monitoring of autoimmune psychosis is still limited.MethodsA two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationships between three autoimmune diseases (SLE, SS, and HT, n = 14,267 to 402,090 individuals) and 191 rsfMRI phenotypes (n = 47,276 individuals), as well as 338 CSF metabolites. The genome-wide association study (GWAS) of three autoimmune diseases was used as the exposure, whereas rsfMRI phenotypes and 338 CSF metabolites were treated as the outcome. Inverse variance weighted (IVW) with P value < 0.05 was regarded as the primary approach for calculating causal estimates. Additionally, the false discovery rate (FDR)-adjusted P value (PFDR) < 0.05 was utilized to account for multiple testing. MR Egger method, weighted median method, simple mode method and weighted mode method were used for sensitive analysis.ResultsOur analyses identified 5 causal relationships between SLE and the 191 rsfMRI phenotypes, 48 between SS and the 191 rsfMRI phenotypes, and 4 between HT and the 191 rsfMRI phenotypes. Additionally, we found 8 causal relationships between HT and CSF metabolites. Furthermore, all three diseases were significantly associated with the temporal lobe and triple networks (default mode network (DMN), salience network (SN), and central executive network (CEN)), which are the core brain regions and functional networks for cognition. Following FDR correction, 6 causal relationships between SS and the 191 rsfMRI phenotypes were further validated.ConclusionsOur study pinpoints important brain functional networks and CSF metabolites potentially implicated in the pathogenesis of psychiatric disorders associated with autoimmune diseases and highlights critical brain regions for the development of novel therapeutics.

Identification of mitochondrial function and programmed cell death associated key biomarkers and the circRNA-miRNA-mRNA regulatory network in systemic lupus erythematosus

ObjectivesSystemic Lupus Erythematosus (SLE) is a highly heterogeneous autoimmune disease with complex pathogenic mechanisms. Mitochondrial function and programmed cell death (PCD) play important roles in SLE. This study aims to screen biomarkers related to mitochondrial function and programmed cell death in SLE and analyze their underlying mechanisms.MethodsSLE-related databases were derived from the GEO database, where three SLE databases were merged into one database as the training set. Genes related to mitochondrial function and PCD were sourced from the MitoCarta 3.0 database. Key genes were identified through bioinformatics and machine learning, and their expression levels and diagnostic efficacy were validated using two SLE-related datasets as the validation set. The relationship between diagnostic genes and immune cells was analyzed through CIBERSORT immune infiltration analysis. Diagnostic genes-related miRNAs were predicted using online databases. Differential circRNAs were screened in SLE circRNA datasets, and the relationship between circRNAs and miRNAs is predicted through circbank, finally constructing a circRNA-miRNA-mRNA ceRNA regulatory network.ResultsFrom the 448 differential genes in the SLE training set, two key genes, IFI27 and LAMP3, were identified through machine learning and WGCNA. Enrichment analysis revealed that they were mainly enriched in pathways such as cell cycle, systemic lupus erythematosus, cytosolic DNA sensing pathway, toll-like receptor (TLR) signaling pathway and nod-like receptor (NLR) signaling pathway. Immune infiltration analysis found that compared with normal group, 11 immune cells were differentially expressed, with IFI27 related 9 types of immune cells and LAMP3 related 10 types of immune cells. The final constructed circRNA-miRNA-mRNA ceRNA regulatory network consists of 2 mRNAs, 5 miRNAs, and 4 circRNAs.ConclusionOur study ultimately identified two biomarkers (IFI27 and LAMP3) related to mitochondrial function and programmed cell death that play an important role in SLE. In the future, IFI27 and LAMP3 have the potential to become important biomarkers in the diagnosis and treatment of SLE. Their role in the immune response may provide new strategies for the treatment of SLE.

Exploring endothelial dysfunction in major rheumatic diseases: current trends and future directions.

The relationship between rheumatic diseases (RDs) and endothelial dysfunction (ED) is intricate and multifaceted, with chronic inflammation and immune system dysregulation playing key roles. RDs, including Osteoarthritis (OA), Rheumatoid arthritis (RA), Systemic Lupus erythematosus (SLE), Ankylosing spondylitis (AS), Psoriatic arthritis (PsA), Sjogren's syndrome (SS), Systemic sclerosis (SSc), Polymyalgia rheumatica (PMR) are characterized by chronic inflammation and immune dysregulation, leading to ED. ED is marked by reduced nitric oxide (NO) production, increased oxidative stress, and heightened pro-inflammatory and prothrombotic activities, which are crucial in the development of cardiovascular disease (CVD) and systemic inflammation. This association persists even in RD patients without conventional cardiovascular risk factors, suggesting a direct impact of RD-related inflammation on endothelial function. Studies also show that ED significantly contributes to atherosclerosis, thereby elevating cardiovascular risk in RD patients. This review synthesizes the molecular mechanisms connecting major RDs and ED, highlighting potential biomarkers and therapeutic targets. Ultimately, the review aims to enhance understanding of the complex interactions leading to ED in rheumatic patients and inform strategies to mitigate cardiovascular risks and improve patient outcomes.