Search Results (1,071)

Background: Interleukin-6 (IL-6) is a multifunctional cytokine implicated in various inflammatory and immune-mediated processes. Its involvement in systemic lupus erythematosus (SLE) has been increasingly investigated, particularly related to disease activity and tissue damage. This study aimed to quantify serum IL-6 levels in patients with SLE and assess their associations with clinical manifestations and laboratory parameters. Methods: A total of 88 patients diagnosed with SLE and 87 matched healthy controls were included. Serum IL-6 concentrations were measured by ELISA. Clinical data, SLEDAI scores, organ involvement, inflammatory markers, and autoantibody profiles were recorded. The statistical analysis involved non-parametric testing, correlation analysis, and linear regression. Results: IL-6 concentrations were higher in SLE patients than in controls (7.46 ± 6.73 vs. 5.30 ± 10.89 pg/mL). Significantly increased IL-6 levels were observed in patients with active disease (SLEDAI ≥ 6; p = 0.025) and renal (p = 0.001) involvement. Positive correlations were identified between IL-6 and ESR, creatinine, ANA, and specific autoantibodies (anti-dsDNA, SSA, and SSB). IL-6 also correlated with IL-10 (p = 0.010) but showed no significant association with IL-17A, TNF-α, CRP, or complement levels. Conclusions: Elevated IL-6 levels are associated with greater disease activity and specific organ involvement in SLE. These findings highlight IL-6 as a measurable indicator of immunological and clinical disease expression, supporting its relevance in disease monitoring. Full article

Natural Deep Eutectic Solvents (NADES) were synthesized from food-grade components and evaluated as green extractants for the simultaneous recovery and liquid chromatography coupled to quadrupole-Orbitrap mass spectrometry (LC–Q-Orbitrap-MS) analysis of biopesticide residues in a complex matrix like honey. Conventional solid–liquid extraction (SLE) was applied, initially using choline chloride-2,3-butanediol (1:4, molar ratio) as the NADES extractant solvent, before systematically evaluating other NADES formulations. Extraction parameters, such as time (10 min, 20 min, and 30 min), technique (rotary mixing vs. sonication), and NADES composition, namely lactic acid–glucose–water (LGH, 5:1:9, molar ratio), lactic acid–glycerol–water (LGLH, 1:1:3, molar ratio), urea–glycerol–water (UGLH, 1:1:2, molar ratio), and choline chloride–2,3-butanediol (ChClBt, 1:4, molar ratio), were systematically optimized. Rotating agitation for 10 min yielded the highest overall recoveries and was therefore selected as the optimal extraction time. Rotary shaking was chosen over sonication due to its superior performance across both simple and complex matrices. Among the NADES tested, UGLH proved to be the most effective composition for the honey matrix. The analytical method was validated for the honey matrix. Linearity showed excellent performance across the tested concentration range, with R² values above 0.95 for all analytes. Matrix effects were within ±20% for nearly half of the compounds, while a few exhibited moderate matrix enhancement. Recoveries ranged from 50.1% to 120.5% at 500 µg/kg and 1000 µg/kg, demonstrating acceptable extraction performance. Intra-day and inter-day precision showed relative standard deviations (RSDs) below 20% for most analytes. Limits of quantification (LOQs) were established at 500 µg/kg for eight compounds based on recovery and precision criteria. These results confirm the suitability of the proposed NADES-based method for sensitive and reliable analysis of biopesticide residues in honey. When compared to conventional extraction methods, the proposed NADES-based protocol proved to be a greener alternative, achieving the highest AGREEprep score due to its use of non-toxic solvents, lower waste generation, and overall sustainability. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a broad and varied clinical presentation. In the absence of definite diagnostic criteria, establishing an SLE diagnosis remains challenging. This case series illustrates that other diseases, such as primary immunodeficiencies and monogenic interferonopathies, can closely mimic SLE, even in the presence of its typical serological markers. Recognizing these disease mimickers is crucial to avoid premature conclusions in clinical evaluation and to ensure the initiation of appropriate therapy. Especially in cases of atypical presentation, unusual disease progression, or resistance to standard therapy, alternative diagnoses should be considered. In this overview, we discuss the diagnostic approach for patients with SLE-like manifestations and provide a comprehensive review of diseases that may mimic SLE. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems, characterized by remissions and relapses. Musculoskeletal involvement occurs in up to 95% of patients and may present as the initial symptom in 50%. Such involvement is often subclinical, without obvious joint or tendon inflammation. Musculoskeletal ultrasound (US) has proven valuable for detecting pathological changes in joints and periarticular structures, including in SLE patients, and early detection, particularly in subclinical stages, supports optimal therapy, monitoring, and improved prognosis. This study aimed to determine the frequency of new clinical manifestations in patients with previously confirmed clinical and subclinical musculoskeletal inflammation after 2 and 5 years, and to evaluate associations with sex, age, BMI, smoking status, ESR, CRP, SLEDAI-2K, complement components C3 and C4, anti-dsDNA antibodies concentrations, and prior treatment. Methods: The study included 34 SLE patients with clinical and 22 with subclinical musculoskeletal inflammation, confirmed at baseline by history, examination, and US. Follow-up at 2 and 5 years recorded new clinical manifestations. Correlations with patient characteristics were assessed to identify predictors. Results: New clinical manifestations occurred in 34% of patients at 2 years and 48% at 5 years, most commonly cutaneous, musculoskeletal, and hematological. Summary analysis identified female sex, lower BMI, and lower baseline SLEDAI-2K scores as the strongest predictors. In the subclinical group, female sex, smoking, and lower SLEDAI-2K scores were predictive, while in the clinical group, female sex, lower SLEDAI-2K scores, lower ESR, and higher anti-ds DNA levels were associated with new manifestations. Conclusions: Female sex, lower BMI, and lower baseline SLEDAI-2K scores are key predictors of new clinical manifestations in SLE patients, highlighting the importance of early detection and individualized monitoring, particularly in patients with subclinical musculoskeletal inflammation. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is associated with impaired functional capacity, persistent fatigue, and poor health-related quality of life despite advances in pharmacological therapy. Exercise training has been proposed as a non-pharmacological intervention, but its efficacy and safety remain incompletely defined. This systematic review aimed to evaluate the effects of exercise training on functional aerobic capacity and quality of life in adults with SLE. Methods: A comprehensive search of PubMed, EMBASE, Cochrane Library, and PEDro was conducted to identify randomized controlled trials published up to October 2022, in accordance with the PRISMA guidelines. Results: Twelve randomized controlled trials involving 619 participants were included. Exercise interventions were heterogeneous and comprised aerobics, resistance, combined programs, vibration training, home-based protocols, and counseling strategies, with durations ranging from 6 weeks to 12 months. Supervised aerobic and combined interventions consistently improved functional aerobic capacity, while quality of life benefits were reported across several domains, particularly physical health, vitality, and fatigue. Additional positive effects were observed on fatigue, depression, pain, sleep, insulin sensitivity, and self-care ability, without evidence of increased disease activity. Conclusions: Structured exercise is safe and can meaningfully enhance functional capacity and quality of life in patients with SLE, supporting its incorporation into multidisciplinary clinical management. Full article

Antinuclear antibodies, especially anti-DNA antibodies, are known to be a hallmark of systemic lupus erythematosus (SLE) and represent a diverse pool of autoantibodies with different origins, antigenic properties, and physicochemical features. Antibodies with catalytic properties have been found among the antibody repertoire in SLE, but the specific features and clinical associations of such antibodies have not been sufficiently studied. This study showed that chromatographically purified IgG from the serum of SLE patients effectively hydrolyzed DNA and DNA-associated proteins such as histones and high-mobility group box 1 (HMGB1) compared to healthy individuals. Remarkably, the level of hydrolysis of DNA and DNA-associated proteins was closely correlated. At the same time, these antibodies did not hydrolyze the control protein, tumor necrosis factor-α (TNFα), which does not possess DNA-binding properties. IgG DNase activity levels varied significantly, so patients were divided into high- and low-activity subgroups using the DBSCAN algorithm, with the difference between median values being greater than 49 times. The subgroup with high IgG DNase activity was characterized by an increase in anti-DNA antibodies (p < 0.04) than the subgroup with low activity, which had a shorter duration of the disease (p = 0.03) and was more often characterized by a subacute rather than a non-chronic course of the disease (p = 0.048). High catalase-like activity of IgG was also detected in SLE. Thus, the antibody pool in SLE contains not only high-affinity antinuclear autoantibodies but also catalytic antibodies capable of hydrolyzing DNA and DNA-associated proteins. These findings expand our understanding of the heterogeneity of the repertoire of catalytic autoantibodies among SLE patients. Full article

Non-viral myocarditis is rare but relatively more frequent in patients with systemic autoimmune diseases (such as systemic lupus erythematosus, SLE, and allied conditions) than in the general population. In rare cases, mRNA-based vaccines can also trigger non-viral myocarditis. Limited data are available about the cardiac safety of mRNA vaccines in this subset of patients. Here, we report data from a third-level hospital on long-term safety, leveraging on a previously described cohort of 13 consecutive patients with SLE, Undifferentiated (UCTD) and Mixed Connective Tissue disease (MCTD), and a history of myocarditis, who had received anti-COVID-19 vaccination between April 2021 and January 2022. Demographics and clinical data (including validated clinometric for SLE) were collected at baseline, at the first available visit following the primary vaccination cycle, after an additional 12 months, and at the last available follow-up after at least 36 months. Twelve patients, seven females, ten with SLE, one MCTD, and one UCTD, had a median follow-up of 41 (35–45) months. One patient was lost at follow-up. No disease flare or sign of myocarditis recurrence were observed. At last visit, all patients were in a low disease activity state (LLDAS), and all but one were in remission, according to the Definition of Remission in SLE (DORIS) criteria. No significant variations in disease activity or damage accrual nor in markers of inflammation and myocardial injury were observed. Our data suggest that mRNA-based anti-COVID-19 vaccines in patients with previous autoimmune myocarditis in the context of SLE and allied conditions have a good long-term safety profile. Full article

Systemic lupus erythematosus (SLE) and other systemic autoimmune rheumatic diseases (SARDs) require long-term immunosuppressive therapy, placing patients at increased risk of infection. Salmonella species are particularly concerning due to their invasiveness and potential link to autoimmune activation, notably in SLE. This study aimed to compare the risk of culture-confirmed Salmonella infection between SLE and other SARDs, based on data from the Chang Gung Research Database between 2005 and 2020. After propensity score matching, 3537 patients per group were analyzed. Patients with SLE had a higher incidence of Salmonella infection compared with those with other SARDs (0.54 vs. 0.17 per 1000 person-years), with a significantly greater cumulative incidence (log-rank p < 0.01). The adjusted hazard ratio (HR) for Salmonella infection in SLE was 2.47 (95% confidence interval (CI): 0.95–6.38), and the competing risk model confirmed a significant association (sub-distribution HR 2.58, 95% CI: 1.06–6.29, p = 0.04). Among SLE patients, lymphopenia was the only independent predictor of Salmonella infection (adjusted HR 3.98, 95% CI: 1.83–8.68, p < 0.001). Bloodstream infections were most common (70%), and serogroup D was the predominant strain (80%). These results suggest patients with SLE face higher Salmonella risk than other SARDs, especially those with lymphopenia, underscoring the need for targeted surveillance and preventive strategies. Full article

Background: Anti-dsDNA is an important biomarker for the diagnosis, prognosis, and monitoring of systemic lupus erythematosus (SLE). Although several assays for anti-dsDNA antibody detection are routinely used, standardization remains limited, and differences have been reported. This study aimed to compare five methods for anti-dsDNA antibody detection and to estimate their association with complement consumption. Methods: A total of 149 samples submitted for routine laboratory testing were collected and tested on five platforms: Crithidia luciliae indirect immunofluorescence test (CLIFT), addressable laser bead immunoassay (ALBIA), a high-avidity (HA) enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay (CIA), and a novel particle-based multi-analyte technology (PMAT). Complements C3 and C4 were available for a subset of the total samples. Results: Correlation between anti-dsDNA assays ranged from 0.94 (CIA and PMAT) to 0.65 (ALBIA and CLIFT). The AUC from the ROC analysis using CLIFT as a reference was 0.95 for PMAT, 0.94 for CIA, 0.93 for ELISA, and 0.86 for ALBIA. The highest sensitivity relative to CLIFT at a fixed specificity of 94.4% was 84.7% for CIA and ELISA, 76.3% for PMAT, and 42.4% for ALBIA. Correlation between anti-dsDNA and C3 ranged from −0.81 for ELISA to −0.51 for ALBIA. Conclusions: Different anti-dsDNA detection methods showed varying diagnostic performance and correlation and varying agreement with CLIFT and complement consumption. ELISA, CIA, and PMAT showed high correlation to each other and to CLIFT and were in strong concordance with low C3 levels. In contrast, ALBIA revealed lower clinical performance and correlation with CLIFT and complement consumption. Full article

Background and Objectives: Lupus nephritis (LN) is a major cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE). Biomarkers derived from blood, urine, and multi-omics techniques are essential for enabling access to less invasive methods for LN evaluation and personalized precision medicine. Materials and Methods: The purpose of this work was to review the studies that addressed the potential role of urinary and serological biomarkers for the diagnosis, disease activity, response to treatment, and renal outcome of adult patients with LN, published over the past decade, and summarize their results with a particular emphasis being directed towards the available traditional tools. Results: Traditional biomarkers used for the diagnosis and surveillance of LN are proteinuria, urinary sediment, estimated glomerular filtration rate (eGFR), anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-C1q, and serum complement levels. Anti-dsDNA, serum C3, and proteinuria are the conventional biomarkers with the strongest clinical evidence, with overall moderate ability in predicting LN from non-renal SLE, disease activity, renal flares, response to therapy, and prognosis. The last decade has brought significant progress in our understanding regarding the pathogenesis of LN and, consequently, several molecules, either alone or in combination panels, have emerged as potential novel biomarkers, some of them outperforming conventional biomarkers. Promising results have been suggested for urinary activated leukocyte cell adhesion molecule (ALCAM), soluble cluster of differentiation 163 (CD163), C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein 1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and vascular cell adhesion molecule 1 (VCAM-1). Conclusions: Despite the intensive research of the last decade, no novel biomarker has entered clinical practice, and we continue to rely on traditional biomarkers to assess non-invasively LN and guide its treatment. Novel biomarkers should be validated in multiple longitudinal independent cohorts, compared with conventional biomarkers, and integrated with renal histology information in order to optimize the management of LN patients. Full article

N⁶-methyladenosine (m⁶A) has recently emerged as a post-transcriptional modulator governing cell-specific gene expression in innate immune cells, particularly in monocytes. Disruptions in m⁶A homeostasis, manifested as the altered expression of m⁶A-related proteins and m⁶A levels, have been implicated in autoimmune disorders. Perturbations in m⁶A dynamics within total Peripheral blood mononuclear cells (PBMCs) have shown strong correlations with disease severity in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It remains unclear in which specific cell type(s) m⁶A homeostasis is disturbed, and also whether other rheumatic diseases such as juvenile idiopathic arthritis (JIA) show similar features. Here, we assess the involvement of m⁶A and m⁶A-regulatory proteins in JIA monocytes. Notably, the diminished expression of m⁶A-eraser proteins FTO and ALKBH5 was observed in JIA monocytes extracted from the inflamed joint. This resulted in increased m⁶A-methylated transcripts in monocytes from these patients. Correspondingly, we observed that culturing monocytes in the presence of synovial fluid from JIA inflamed joints reduced the expression of both FTO and ALKBH5. The knock-out of FTO in human monocytes of healthy controls increased monocyte activation, indicating the relevance of FTO and m⁶A in the context of JIA. These findings underscore the potential of ALKBH5 and FTO expression as a biomarker in JIA and identify the m⁶A machinery as a potential therapeutic target for the treatment of JIA and possibly other autoimmune diseases in the future. Full article

Background/Objectives: In clinical informatics, the term ‘information overload’ is increasingly used to describe the operational impediments of excessive documentation. While electronic health records (EHRs) are growing in abundance, many medical records (MRs) remain in legacy formats that impede efficient, systematic processing, contributing to the extenuating challenges of care fragmentation. Thus, there is a growing interest in using generative AI (genAI) for automated MR summarization and characterization. Methods: MRs for a set of 78 individuals were digitized. Some were known systemic lupus erythematosus (SLE) cases, while others were under evaluation for possible SLE classification. A two-pass genAI assessment strategy was implemented using the Claude 3.5 large language model (LLM) to mine MRs for information relevant to classifying SLE vs. undifferentiated connective tissue disorder (UCTD) vs. neither via the 22-criteria EULAR 2019 model. Results: Compared to clinical determination, the antinuclear antibody (ANA) criterion (whose results are crucial for classifying SLE-negative cases) exhibited favorable sensitivity 0.78 ± 0.09 (95% confidence interval) and a positive predictive value 0.85 ± 0.08 but a marginal performance for specificity 0.60 ± 0.11 and uncertain predictivity for the negative predictive value 0.48 ± 0.11. Averaged over the remaining 21 criteria, these four performance metrics were 0.69 ± 0.11, 0.87 ± 0.04, 0.54 ± 0.10, and 0.93 ± 0.03. Conclusions: ANA performance statistics imply that genAI yields confident assessments of SLE negativity (per high sensitivity) but weaker positivity. The remaining genAI criterial determinations support (per specificity) confident assertions of SLE-positivity but tend to misclassify a significant fraction of clinical positives as UCTD. Full article

Fibrosis is a pathological process characterized by the excessive accumulation of extracellular matrix (ECM), particularly collagen, leading to tissue scarring, architectural distortion, and organ dysfunction. While fibrosis is a physiological component of wound healing, its persistence and dysregulation can drive chronic tissue damage and organ dysfunction. In autoimmune diseases, fibrosis arises from prolonged inflammation and immune system dysregulation, creating a vicious cycle that exacerbates tissue injury and promotes disease progression. This review provides a comprehensive overview of the fibrotic processes across a range of immune-mediated and autoimmune conditions, including systemic sclerosis (SSc), morphea, autoimmune hepatitis (AIH), systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA), Finally, we discuss current and emerging antifibrotic strategies aimed at interrupting pathological ECM remodeling and restoring tissue homeostasis. Full article

Galectin-1 and -9 (Gal1/9) are essential mediators of immune-inflammatory responses, which makes these proteins potential biomarkers for immune-mediated diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis (PS), psoriatic arthritis (PsA), inflammatory bowel disease, and systemic lupus erythematosus (SLE). Our aim was to evaluate plasma Gal1/9 differences between IMID patients and healthy donors (HD). We analyzed 980 plasma samples divided into two analytical cohorts (600 discovery group and 380 validation group). Generalized linear models estimated Gal1/9 levels, adjusting for sex, age, storage time, and plate variability. In the overall IMID group, plasma Gal1 levels were comparable to those of HD, while Gal9 levels were significantly elevated. Levels varied across individual diseases: SLE patients consistently showed the highest Gal1/9 levels compared to both HD and other IMIDs, and RA patients had elevated Gal9 levels versus HD. Both Gal1 and Gal9 plasma levels correlated positively with higher disease activity, and Gal1 was higher in patients with longer disease duration. After adjustment for these confounders, SLE and RA patients maintained the highest Gal9 levels compared to HD. Our study demonstrates that Gal1 and Gal9 are differentially expressed across IMIDs, with particularly elevated levels in SLE, and both galectins are associated with disease activity. Full article

Neutrophils, a first-line defender, has a multifaceted presence in chronic inflammation, autoimmune pathology, and tumor progression. The microenvironmental cues facilitate functional plasticity and phenotypic heterogeneity to neutrophils that enable both their protective and pathogenic roles. Autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA) display the presence of dysregulated subsets of neutrophil, such as low-density granulocytes (LDGs) that promote proinflammation and contribute to tissue damage via NETosis and type I interferon-mediated signaling. In cancer, particularly tumors, they exhibit tumor-associated neutrophils (TANs) which may polarize either towards anti-tumorigenic ‘N1’ or pro-tumorigenic ‘N2’ phenotypes based on available modulators such as TGF-β and leucine-driven epigenetic modifications. The development in neutrophil biology has introduced several novel therapeutic strategies that allow NET targeting, inhibition of chemokine receptors like CXCR2, and exploration of neutrophil-derived biomarkers for diagnosis and disease monitoring. Such findings encourage the importance of neutrophils as both effectors and therapeutic targets in inflammatory and neoplastic conditions. Full article