Search Results (1,348)

Prostaglandins (PGs) are eicosanoid compounds with various hormone-like effects within the human body. Prostaglandin D2 (PGD2), prostaglandin J2 (PGJ2, a metabolite of PGD2), and prostaglandin E2 (PGE2) are common prostaglandins. They are produced from arachidonic acid by cyclooxygenase isoenzymes (COX-1 and COX-2) and PG synthases and are involved in many biological metabolisms, including the inflammatory response. Recent studies show PGs are mediators for both proinflammatory and anti-inflammatory processes. In systemic lupus erythematosus (SLE), inflammation caused by autoimmunity damages tissues, leading to organ diseases such as lupus nephritis and lupus myocarditis. However, the roles of different types of PGs in the pathogenesis of SLE remain unclear. In this review, we discuss three types of PGs—PGD2, PGJ2, and PGE2—for their potential roles in SLE pathogenesis. Full article

Systemic lupus erythematosus (SLE) disproportionately affects women and often disrupts work, intimate relationships, and reproductive life. Although stigma is increasingly recognized in chronic illness, less is known about how it is experienced among women with SLE in China. Using an interpretive phenomenological design informed by health stigma theory, this qualitative study examined how stigma was produced, experienced, and managed in the everyday lives of 20 Chinese women living with SLE. Data were generated through semi-structured online interviews, chosen because of participants’ geographic dispersion and health-related constraints, and analyzed using an iterative thematic approach. The findings show that stigma operated through interconnected forms: visible bodily stigma linked to treatment-related appearance changes, invisible-symptom stigma that demanded ongoing credibility work, institutional stigma in employment, and gendered stigma in intimacy and motherhood. Participants responded through concealment, selective disclosure, and narrative labor: the work of presenting themselves as credible, responsible, and morally worthy despite social devaluation. These findings suggest that SLE stigma is not only interpersonal but also institutional and gendered, highlighting the need for stigma-sensitive clinical communication, workplace support, and reproductive counseling for women living with chronic illness. Full article

Background: Immune dysregulation and clinical immunosuppression are biologically plausible contributors to thoracic aortic wall vulnerability through endothelial injury, protease-mediated extracellular matrix remodeling, vascular smooth muscle cell dysfunction, and impaired vascular repair. Yet, the clinical relevance of immunomodulated states to thoracic aortic aneurysm (TAA) incidence or growth and acute aortic syndromes remains undefined. Methods: This comprehensive review synthesizes clinical and translation evidence linking immunomodulated states in solid organ transplantation, autoimmune disease (predominantly systemic lupus erythematosus), HIV, and oncologic therapies to thoracic aortic dilation, aneurysmal progression, and acute aortic events. Principal Findings: Across transplant, autoimmune, and HIV cohorts, recurring themes include chronic immune dysregulation, endothelial dysfunction, proteolytic matrix remodeling, and impaired vascular repair capacity, although thoracic segment-specific longitudinal growth data remain limited and are often embedded within analyses of multiple vascular beds. In oncologic cohorts, aggregate analyses generally do not demonstrate uniform acceleration of aneurysm growth with malignancy or chemotherapy exposure, although agent-level models suggest that regimen-specific effects may be obscured in pooled estimates. Two studies most directly addressed our question in thoracic-relevant contexts reported (1) very low mean annual ascending aortic aneurysm growth (0.18 ± 0.64 mm/year) with no detectable association with chemotherapy or radiotherapy and (2) prior immunosuppressive/cytostatic chemotherapy exposure to be common in a proximal TAA surgical cohort (39.3%) without a clear difference in thoracic phenotype at presentation or postoperative outcomes. In HIV cohorts, available evidence supports modest but reproducible proximal aortic remodeling and a clinically meaningful aneurysm burden across vascular beds, yet definitive thoracic segment-specific natural history data remain limited. Conclusions: The available literature supports clinical vigilance and exposure-aware surveillance, while suggesting that thoracic aortic risk is unlikely to be uniform across immunosuppressive and cytotoxic therapies. Standardized, segment-specific longitudinal imaging with granular agent-level exposure characterization (dose, duration, sequencing, and combination regimens), consistent definitions of baseline diameter and growth, careful adjustment for key confounders, and prospective ascertainment of dissection/rupture and operative endpoints are needed to translate immunobiology into actionable risk stratification and long-term management strategies. Full article

Aim: Disturbances in exhausted and classical memory B cells have been implicated in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN), but the genetic regulation of their homeostasis remains poorly understood. Methods: We analyzed the single-cell RNA-seq data of peripheral blood mononuclear cells (PBMCs) from the NIH SLE dataset (GSE135779) and another published LN single-cell RNA-seq dataset (dbGAP database accession code phs001457.v1.p1). Overlapping differentially expressed genes (DEGs) in exhausted and classical memory B cells from SLE and LN patients were identified, and their altered expression was validated in B cells obtained from LN patients. GO and KEGG analyses were used to analyze associated pathways. The relationships between exhausted and classical memory B cells and cellular metabolic pathways were also assessed. Results: Three DEGs (IFI44L, XAF1, and MX1) were detected in both exhausted and classical memory B cells, and their increased expression was verified in classical and exhausted memory B cells obtained from LN patients during remission. The protein–protein interaction network of the DEGs suggested that STAT1 showed the highest eigenvector centrality for these DEGs. IFI44L, XAF1 and MX1 were involved in distinct biological processes and immune pathways (especially JAK-STAT). Classical memory B cells showed higher expression of genes involved in sulfur metabolism (SQRDL and TST), amino sugar metabolism (GFPT1 and UAP1), and butanoate metabolism (ACADS and ACAT1), while exhausted B cells exhibited inverse relationships with these metabolic pathways. Conclusions: Altered expression of IFI44L, XAF1 and MX1 is associated with distinct metabolic signatures and immune pathways in exhausted and classical memory B cells in SLE and LN. Full article

Background/Objectives: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE); it is associated with increased morbidity and mortality, underscoring the need for new diagnostic markers and therapeutic strategies. In this context, the exostosin 1 (EXT1)/exostosin 2 (EXT2) heterodimer has emerged as a novel antigen in membranous nephropathy associated with SLE. This study evaluated EXT1 prevalence in renal biopsies from patients with lupus membranous nephropathy (LMN) and compared clinical, laboratory, and histopathological characteristics on diagnosis and renal outcomes. Methods: This retrospective study included 97 LMN patients whose renal biopsy underwent immunohistochemistry (IHC) for EXT1. EXT1-positive and EXT1-negative groups were compared using descriptive analyses and repeated measures models. Results: EXT1 positivity was observed in 35% of the cohort, and is more frequent in pure LMN (40%) than in cases with a proliferative component (32%). Regarding SLE diagnostic criteria, EXT1-positive patients showed a higher frequency of antiphospholipid antibodies, although data were available for only a subset of patients. This group also exhibited lower serum creatinine levels, but without statistical significance. EXT1-negative patients more frequently received cyclophosphamide as induction therapy (57.6% vs. 34.5%; p = 0.041). No differences in clinical outcomes were observed during follow-up. Conclusions: EXT1 prevalence was consistent with the literature, reinforcing the epidemiological reproducibility of this marker. EXT1-positive and EXT1-negative groups did not differ regarding clinical presentation, disease progression, and renal outcomes, heightening the need for prospective studies to further elucidate the diagnostic and prognostic role of EXT1 in LMN. Full article

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disorder arising from the convergence of genetic susceptibility, epigenetic remodeling, environmental exposures, and dysregulated immune networks. Although traditionally characterized by autoantibody production and immune complex mediated tissue injury, advances in genomics, systems immunology, and multi-omics profiling have revealed that lupus represents a multilayered failure of immune homeostasis driven by interconnected molecular circuits. Genetic variants enriched in regulatory immune enhancers establish a permissive transcriptional landscape that sensitizes innate nucleic acid sensing pathways and interferon signaling. Epigenetic remodeling further amplifies inflammatory transcriptional programs, while environmental triggers such as ultraviolet radiation and viral infection initiate bursts of nucleic acid release and immune activation. Defective apoptotic cell clearance, mediated in part by scavenger receptor dysfunction and complement abnormalities, increases the availability of immunogenic nucleic acids that engage pattern recognition receptors and drive chronic type I interferon production. This interferon-dominated environment rewires immune cell metabolism, alters differentiation trajectories of T and B lymphocytes, and sustains autoreactive immune circuits. Emerging multi-omics studies reveal distinct molecular endotypes defined by interferon signatures, metabolic states, and immune cell composition, highlighting the heterogeneity of disease mechanisms across patients. In this review, we integrate genetic, epigenetic, metabolic, and immunological insights to propose a systems-level model of lupus pathogenesis in which defective debris clearance, nucleic acid sensing, interferon amplification, and metabolic reprograming form a self-reinforcing pathogenic network. Understanding this integrated molecular architecture provides a foundation for biomarker-guided therapeutic strategies and precision medicine approaches aimed at disrupting the key nodes that sustain chronic autoimmunity in SLE. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune dysregulation and multi-organ damage. Abnormal B cell activation and autoantibody production constitute the core pathological mechanism of SLE. However, the proportion, BCR pairing types, clonal evolution patterns, and transcriptomic features of dual BCR B cells in SLE remain incompletely elucidated. In this study, we employed single-cell RNA sequencing (scRNA-seq) combined with single-cell B cell receptor repertoire sequencing (scBCR-seq) to preliminarily analyze the proportion and characteristics of dual BCR B cells in SLE model mice (MRL/Lpr and SLE.Yaa) as well as in peripheral blood from SLE patients. The results showed: (1) Compared with control groups, the proportion of dual BCR B cells in SLE model mice and patients exhibited a decreasing trend, whereas the diversity of the CDR3 repertoire decreased and clonality increased. Increased clonal sharing was observed between single BCR B cells and dual BCR B cells. The main pairing types of dual BCR B cells were H + κ1 + κ2, H1 + H2 + κ, and H1 + H2 + κ + λ, with preferential utilization of autoimmunity-associated V gene families such as IGHV4-34, and high expression of IGHG subtypes. (2) Tracking analysis of B cell receptor clonality and effector molecule expression revealed that in SLE, dual BCR B cells tend to enrich in IFN-α/γ responses, TNF-NFκB inflammation, and complement pathways, and highly express interferon-related genes such as Ly6a, Isg15, MX1, and IFI6. (3) In both single BCR B and dual BCR B cells from SLE patients, the proportion of the naïve B cell subset decreased, whereas the proportions of plasma and Breg subsets increased and exhibited clonal expansion. SLE dual BCR Breg cells highly expressed IL10, HSPA1A, and others. This study is the first to reveal, at the high-throughput single-B-cell level, that the proportion, subset origin distribution, CDR3 repertoire composition, and effector molecule expression of dual BCR B cells display unique characteristics in SLE model mice and patients, providing baseline comparative data and novel research perspectives for further investigation into B cell effector functions and mechanisms in SLE patients. Full article

Mesenchymal stromal cells (MSCs) are multipotent cells characterized by their regenerative capacity and strong immunomodulatory properties. In recent years, MSC-based therapy has attracted significant attention as a potential treatment for a wide range of immune-mediated and degenerative diseases. The therapeutic effects of MSCs are primarily mediated through paracrine signaling and secretion of cytokines that regulate immune responses and promote tissue repair. This review focuses on five key cytokines involved in MSC immunomodulation: interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). These cytokines interact within a complex signaling network that allows MSCs to suppress excessive inflammation and restore immune balance. The role of MSC therapy is examined in several clinically relevant conditions, including systemic lupus erythematosus, systemic sclerosis, ischemic stroke, spinal cord injury, diabetes mellitus, and female infertility. Across these diseases, MSCs demonstrate the ability to inhibit pro-inflammatory immune cell activity, promote regulatory immune phenotypes, reduce oxidative stress, and stimulate regeneration through the secretion of growth factors and extracellular vesicles. Despite promising experimental and early clinical findings, several limitations remain, including variability in MSC sources, limited cell survival after transplantation, and the need for optimized dosing strategies. Overall, MSC therapy represents a multifunctional therapeutic approach combining immunomodulation, anti-inflammatory activity, and regenerative support. Further research is required to better understand cytokine interactions, improve standardization of MSC-based treatments, and enhance clinical efficacy across diverse pathological conditions. Full article

Chimeric antigen receptor (CAR) T-cell therapy represents a major advance in modern immunotherapy. This narrative review summarizes evidence from the past five years, including case reports, case series, and clinical trials, on its application beyond hematologic malignancies, focusing on autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), as well as solid tumors including melanoma and primary cutaneous lymphomas. CD19-directed CAR T-cells have demonstrated clinical benefits in SLE and SSc, with sustained immune reset, reduced autoreactive antibody levels, and clinical improvement. In melanoma, CAR T-cells targeting GD2, cMET, and CD20 have shown in vivo expansion and tumor infiltration; however, clinical efficacy remains limited, with transient stabilization or disease progression in most patients. In primary cutaneous lymphomas, early-phase studies with anti-CD70 and anti-CCR4.30 CAR T-cells indicate partial tumor regression and disease stabilization, often requiring additional therapy. Key challenges include limited durability of immune reset due to persistent plasma cells in autoimmune disorders, tumor heterogeneity, antigen loss or overlap, infiltration barriers, resistance mechanisms, and T-cell depletion in solid tumors, collectively reducing response durability and safety. The main toxicities include grade 1–2 cytokine release syndrome and rare hematologic complications, while immune effector cell-associated neurotoxicity syndrome is uncommon. Clinical translation remains limited and requires larger studies to improve efficacy and define safety profiles. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, with anti-double-stranded DNA (anti-dsDNA) antibodies as its serological biomarkers. However, conventional anti-dsDNA antibody detection methods, which mainly rely on antibody-binding assays, often suffer from limited sensitivity and specificity, cumbersome procedures, and poor suitability for accurate clinical analysis. Herein, we developed an integrated detection system combining a circularly permuted fluorescent protein (cpFP)-based biosensor with a microfluidic chip for rapid and reliable anti-dsDNA antibody detection. The biosensor, cpR-dsAb-C1, was engineered from mApple by inserting an affinity peptide identified through phage display, enabling specific recognition of the variable region of anti-dsDNA antibodies. The biosensor exhibited good sensitivity, specificity, and anti-interference capability. Furthermore, integration of cpR-dsAb-C1 with a polydimethylsiloxane (PDMS)-based microfluidic chip yielded a microfluidic detection platform with good linearity for rapid antibody analysis. Clinical validation showed significantly higher anti-dsDNA antibody levels in patients with SLE than in healthy controls, and the results were consistent with those obtained using routine clinical methods, with an accuracy exceeding 95%. Overall, this system provides a promising low-cost, efficient, and accurate strategy for the early diagnosis and dynamic monitoring of SLE. Full article

Background/Objectives: Long-term outcomes in systemic lupus erythematosus (SLE) are largely driven by irreversible organ damage, yet the relative contribution of comorbid conditions remains insufficiently characterized. We aimed to characterize damage accrual and identify comorbidities associated with damage severity and mortality. Methods: A retrospective study of adult patients with SLE followed at a single-center (2014–2023). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was used to assess damage at last follow-up. Damage was categorized as none (0), mild–moderate (1–2), or severe (≥3). Demographic, clinical, laboratory, treatment, and comorbidity data were extracted from electronic medical records. Multivariable logistic regression and Cox proportional hazards models were applied to identify factors associated with damage severity and mortality. Results: Among 182 patients (84.1% female; mean follow-up 15.6 ± 11.4 years), 59.5% accrued damage, including 30.8% with severe damage. Damage predominantly involved cardiovascular, ocular, neuropsychiatric, and musculoskeletal domains. It was associated with older age, longer disease duration, hematologic and renal involvement, and corticosteroids and immunosuppressive medications. In multivariable analysis, antiphospholipid syndrome (APS) and hypertension emerged as the dominant independent predictors of damage accrual with an odds ratio of 15.70 (95% CI 4.26–57.89, p < 0.001) and 6.46 (95% CI 2.54–16.40, p < 0.001), respectively. Mortality increased with damage severity (16.1% in SDI ≥ 3, 1.9% in SDI 1–2, none in SDI = 0; p < 0.0001). Damage was also associated with increased hospitalizations. Conclusions: Damage accrual is common and strongly predicts mortality. APS and hypertension emerge as dominant, modifiable drivers, supporting integrated cardiovascular and thrombotic risk management in SLE. Full article

Liver involvement in pediatric rheumatologic diseases is an increasingly recognized but often underappreciated clinical issue. Systemic autoimmune and autoinflammatory disorders including juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, systemic vasculitis, and mixed connective tissue disease can all affect hepatic structure and function. The mechanisms of injury are multifactorial, encompassing immune-mediated inflammation, macrophage activation, drug-induced toxicity, and metabolic alterations. Hepatic manifestations range from asymptomatic transaminase elevations to fulminant liver failure, frequently influenced by immunosuppressive therapy and comorbid infections. Early recognition through routine biochemical monitoring, imaging, and targeted autoantibody testing is essential for differentiating primary disease activity from treatment-related injury. Timely, multidisciplinary management involving pediatric rheumatology and hepatology teams can prevent progression to chronic liver disease and optimize outcomes. This review summarizes the current understanding of hepatic pathology in pediatric rheumatology, highlighting diagnostic algorithms, monitoring strategies, and emerging therapeutic considerations. Full article

Background: Lupus nephritis (LN), a major complication of systemic lupus erythematosus, remains a key determinant of morbidity and mortality despite therapeutic progress. Objective: An expert report aims to present multidisciplinary insights from leading Italian centers on current LN management and future perspectives. Methods: Seven specialists—including nephrologists and rheumatologists with expertise in lupus nephritis—addressed key aspects of LN management, including treatment goals, available therapeutic options, treatment selection across disease stages, and emerging strategies. Results: The authors highlight evolving treatment paradigms—shifting from traditional induction–maintenance strategies to early combination regimens integrating biologics such as belimumab and calcineurin inhibitors like voclosporin—aligned with updated EULAR and KDIGO guidelines. Regional experiences underscore individualized therapy tailored by histology, disease activity, and patient profile. Multidisciplinary collaboration between nephrologists and rheumatologists, equitable access to innovative therapies, and integration of registries and digital records are identified as priorities. Conclusions: Emerging agents, including obinutuzumab, anifrolumab, and CAR-T cell therapies, represent promising advances toward steroid-sparing and potentially curative strategies. Continued research, biomarker development, and application of artificial intelligence are pivotal to optimizing outcomes and achieving personalized LN management. Full article

Objective: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and its diagnosis can cause considerable anxiety and uncertainty for those affected. This study aimed to investigate the effect of a one-day educational seminar on disease-specific knowledge among patients with SLE. Additionally, the influence on subjective needs, the cognitive and emotional impact of the disease, and health-related lifestyle were examined. Methods: Patients were randomly assigned in a 1:1 ratio to an intervention group or a waiting list control group. Both groups attended the seminar. Disease-specific knowledge was measured using a multiple-choice questionnaire. The primary objective was the change in knowledge after the intervention. Results: Thirty-nine participants were included in the analysis. The mean score difference between the waiting list control group and the intervention group was 3.4 points out of a maximum of 20 (95% CI 1.8 to 5) immediately after the seminar and 1.6 (95% CI −0.6 to 3.5) three months later. Pooled data from both groups showed an increase in SLE-specific knowledge from 13.7 points to 17.3 points. Three months later, SLE-specific knowledge remained above the initial value at 15.4 points. However, no influence on lifestyle was observed. Conclusion: A one-day seminar can increase disease-specific knowledge and reduce unmet informational needs but does not lead to lifestyle modifications. Full article

Difficult-to-treat systemic lupus erythematosus (D2T-SLE) remains a major unmet challenge in contemporary lupus care, yet it continues to be defined predominantly by clinical non-response rather than underlying biology. Current biomarkers largely quantify inflammatory burden, immune complex activity, or organ damage and do not reliably capture persistent activation of pathogenic pathways under therapy. Emerging multi-omics, single-cell, and longitudinal studies suggest that, in a subset of patients, apparent treatment failure may reflect incomplete attenuation of dominant immune circuits rather than uniformly elevated inflammation. We propose molecular refractoriness in systemic lupus erythematosus (SLE) as sustained, pathway-level immune activity despite apparently adequate, mechanism-directed therapy. We outline the major immune programs implicated in this process—including interferon-enriched, B-cell/plasmablast-associated, neutrophil extracellular trap (NET)-related, cytotoxic T-cell, and cytokine-associated states—and discuss their relevance for biomarker development and precision trial design. Importantly, we emphasize that interferon gene signatures (IGS) should be interpreted as context-dependent and non-specific markers of interferon responsiveness, reflecting combined activity of type I, II, and III interferons, and functioning primarily as predictive rather than mechanistic biomarkers. We further highlight critical limitations of a purely endotype-based model, including the need to distinguish true molecular refractoriness from damage-dominant and pseudo-refractory states, as well as the emerging role of immune-reset strategies such as cluster of differentiation 19 (CD19)-directed chimeric antigen receptor T-cell (CAR-T) therapy, which may overcome refractoriness independently of specific pathway dominance. These observations suggest that difficult-to-treat SLE encompasses biologically heterogeneous states that may not be fully captured by pathway-resolved stratification alone. Reframing D2T-SLE as a biologically heterogeneous state of incomplete immune attenuation may help bridge the gap between clinical treatment failure and mechanism-informed precision medicine in systemic lupus erythematosus. Full article