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16 pages, 2529 KiB  
Article
Association of Gut Dysbiosis with Disease Phenotype and Treatment in Systemic Lupus Erythematosus
by Irene Medina-Martínez, Rocío Gil-Gutiérrez, Jorge García-García, Francisco Javier de la Hera-Fernández, Nuria Navarrete-Navarrete, Mónica Zamora-Pasadas, Norberto Ortego-Centeno, José Luis Callejas-Rubio, Federico García-García, Julio Gálvez-Peralta, Alba Rodríguez-Nogales, María Correa-Rodríguez and Blanca Rueda-Medina
Med. Sci. 2025, 13(3), 151; https://doi.org/10.3390/medsci13030151 (registering DOI) - 23 Aug 2025
Abstract
Introduction: Gut dysbiosis has been associated with the development of autoimmune diseases, including systemic lupus erythematosus (SLE). Although previous studies suggest microbial alterations in SLE, evidence at the species level and its clinical relevance remain limited. This study aimed to characterise the [...] Read more.
Introduction: Gut dysbiosis has been associated with the development of autoimmune diseases, including systemic lupus erythematosus (SLE). Although previous studies suggest microbial alterations in SLE, evidence at the species level and its clinical relevance remain limited. This study aimed to characterise the gut microbiota at species level in SLE patients and evaluate its association with clinical features. Materials and methods: A total of 57 SLE patients and 57 matched controls were included. Faecal samples were collected using the OMNIgene-GUT kit, and microbial DNA was extracted with the Maxwell RSC PureFood GMO kit. Metagenomic sequencing was performed using the Illumina MiSeq platform, and the data was analysed with QIIME2. Microbial diversity and relative abundance were assessed using the phyloseq package, and differentially abundant taxa were identified using DESeq2. Clinical subgroups among SLE patients were identified via k-means clustering. Results: SLE patients exhibited significantly different beta diversity compared to controls (p = 0.001), with increased abundance of Pseudomonadota (3.81% vs. 6.80%, p < 0.05) and decreased Bacteroidota (53.42% vs. 38.04%, p < 0.05). Only 10 bacterial species were consistently present across all SLE samples, including Akkermansia muciniphila, Bacteroides dorei, and Lactobacillus gasseri. Hypertensive patients and those treated with corticosteroids presented a marked depletion of key microbial taxa. Conversely, Belimumab-treated patients displayed a distinct microbiota enriched in species such as Alistipes shahii and Prevotella corporis. Conclusions: This study confirms significant gut microbiota alterations in SLE and pinpoints microbial profiles associated with clinical subgroups. These findings suggest gut dysbiosis may contribute to SLE pathogenesis and indicate biomarkers for disease stratification. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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16 pages, 2017 KiB  
Article
Assessment of Serum Endocan Levels and Their Associations with Arterial Stiffness Parameters in Young Patients with Systemic Lupus Erythematosus
by Ágnes Diószegi, Hajnalka Lőrincz, Eszter Kaáli, Sára Csiha, Judit Kaluha, Éva Varga, Dénes Páll, Tünde Tarr and Mariann Harangi
J. Clin. Med. 2025, 14(17), 5955; https://doi.org/10.3390/jcm14175955 (registering DOI) - 23 Aug 2025
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with premature atherosclerosis and vascular impairment. However, the role of endocan, a biomarker of glycocalyx injury, is not completely clarified in the detection of vascular damage. Therefore, our aim was to investigate [...] Read more.
Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with premature atherosclerosis and vascular impairment. However, the role of endocan, a biomarker of glycocalyx injury, is not completely clarified in the detection of vascular damage. Therefore, our aim was to investigate serum endocan in comparison with conventional inflammatory markers, arterial stiffness parameters, and carotid ultrasound findings in a cohort of young patients with SLE. Methods: We enrolled 47 clinically active young SLE patients (40 females and 7 males) in the study. Arterial stiffness indicated by augmentation index and pulse wave velocity (PWV) was measured by arteriography. Brachial artery flow-mediated dilatation and common carotid intima-media thickness were detected by ultrasonography. The serum concentrations of endocan, IL-6, MPO, MCP-1, MMP-3, -7, and -9, as well as TNFα, were measured by an enzyme-linked immunosorbent assay (ELISA). Results: We found significant negative correlations between serum endocan and both CH50 and C3. Serum endocan was higher in active SLE patients compared to inactive patients, however, the difference was not statistically significant (241.4 (183–295) vs. 200.3 (167–278) pg/mL; p = 0.313). Serum TNFα and hsCRP significantly correlated with PWV. However, we did not detect significant correlations between vascular diagnostic tests and serum endocan levels. Conclusions: Based on our results, serum endocan is associated with disease activity; however, further studies are needed to clarify the value of serum endocan in the cardiovascular risk estimation of SLE patients. Measurement of serum endocan, as well as the routine assessment of arterial stiffness parameters, should be integrated into the comprehensive management plans of young patients with SLE. Full article
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26 pages, 6593 KiB  
Article
Pulsed Electric Field-Assisted “Green” Extraction of Betalains and Phenolic Compounds from Opuntia stricta var. dillenii Prickly Pears: Process Optimization and Biological Activity of Green Extracts
by Iván Gómez-López, Annachiara Pirozzi, Serena Carpentieri, María P. Portillo, Gianpiero Pataro, Giovanna Ferrari and M. Pilar Cano
Foods 2025, 14(17), 2934; https://doi.org/10.3390/foods14172934 - 22 Aug 2025
Abstract
Opuntia stricta var. dillenii (OPD) fruits are rich in betalains and phenolic compounds, which are recognized for their potential health-promoting properties. This study focuses on the optimization of pulsed electric field (PEF)-assisted solid–liquid green extraction (SLE) from OPD whole fruit, using response surface [...] Read more.
Opuntia stricta var. dillenii (OPD) fruits are rich in betalains and phenolic compounds, which are recognized for their potential health-promoting properties. This study focuses on the optimization of pulsed electric field (PEF)-assisted solid–liquid green extraction (SLE) from OPD whole fruit, using response surface methodology (RSM) experimental design to obtain green extracts rich in bioactive compounds. The optimal PEF pre-treatment conditions (electric field strength and energy input) were determined based on the cell disintegration index (Zp), followed by optimizing SLE conditions (temperature, time, and ethanol content). High-performance liquid chromatography (HPLC-DAD-ESI-Qtof) was used to characterize the individual bioactive compound profile of the obtained OPD green extracts. Results showed that optimal PEF pre-treatment conditions were at 10.5 kJ/kg and 5 kV/cm, followed by SLE at 35 °C for 165 min, using water as the solvent. Conventional optimal SLE conducted at 45 °C, 8% ethanol, and 128 min was applied as the control process. The combined PEF-assisted SLE process enhanced total betalain and phenolic compound yields by 61% and 135%, respectively. Antioxidant activities (DPPH by 145%, FRAP by 28%) and anti-inflammatory potential (hyaluronidase inhibition by 19%) were also significantly improved. This study underscores the potential use of a PEF pre-treatment to improve obtaining green extracts rich in bioactive compounds with high biological activities from OPD whole fruits, using water as a solvent. Full article
15 pages, 1730 KiB  
Article
Effects of Strawberry Leaf Extract on the Quality Characteristics and Oxidation Stability of Dry Fermented Sausage During Ripening and Storage
by Ieva Račkauskienė, Jordi Rovira, Isabel Jaime, María Luisa González-San José and Petras Rimantas Venskutonis
Appl. Sci. 2025, 15(17), 9240; https://doi.org/10.3390/app15179240 - 22 Aug 2025
Viewed by 42
Abstract
Strawberry leaf extract (SLE) was used in dry fermented sausages, “Salchichón”, to enrich them with antioxidants. The effect of SLE on various characteristics was monitored during ripening and storage. SLE had a slight effect on microbiological characteristics; however, the pH after 3, 14, [...] Read more.
Strawberry leaf extract (SLE) was used in dry fermented sausages, “Salchichón”, to enrich them with antioxidants. The effect of SLE on various characteristics was monitored during ripening and storage. SLE had a slight effect on microbiological characteristics; however, the pH after 3, 14, and 21 days was slightly lower (4.51–4.55) in the samples with higher SLE concentration (0.5% + 1% dextrose). Peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) values of sausages with SLE and with ascorbic acid (reference antioxidant), at the end of ripening, were similar. SLE acted as a pro-oxidant when the sausage was stored in the light; however, it showed antioxidant activity in the dark and at 50 °C storage conditions. Higher extract concentration reduced redness a* value and increased yellowness b* value in the CIELab colour system. Addition of SLE to dry fermented sausages has no negative effect on the ripening process; however, storage conditions of the final product should be carefully controlled. Sensory analysis of the final product showed that SLE imparts a recognisable herbal odour; however, it did not reduce the overall product acceptability. It may be concluded that SLE may be a promising ingredient for increasing the nutritional quality of fermented sausages. Full article
(This article belongs to the Section Food Science and Technology)
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25 pages, 336 KiB  
Review
Modeling and Simulation Tools for Smart Local Energy Systems: A Review with a Focus on Emerging Closed Ecological Systems’ Application
by Andrzej Ożadowicz
Appl. Sci. 2025, 15(16), 9219; https://doi.org/10.3390/app15169219 - 21 Aug 2025
Viewed by 99
Abstract
The growing importance of microgrids—linking buildings with distributed energy resources and storage—is driving the evolution of Smart Local Energy Systems (SLESs). These systems require advanced modeling and simulations to address growing complexity, decentralization, and interoperability. This review presents an analysis of commonly used [...] Read more.
The growing importance of microgrids—linking buildings with distributed energy resources and storage—is driving the evolution of Smart Local Energy Systems (SLESs). These systems require advanced modeling and simulations to address growing complexity, decentralization, and interoperability. This review presents an analysis of commonly used environments and methods applied in the design and operation of SLESs. Particular emphasis is placed on their capabilities for multi-domain integration, predictive control, and smart automation. A novel contribution is the identification of Closed Ecological Systems (CES) and Life Support Systems (LSSs)—fully or semi-isolated environments designed to sustain human life through autonomous recycling of air, water, and other resources—as promising new application domains for SLES technologies. This review explores how concepts developed for building and energy systems, such as demand-side management, IoT-based monitoring, and edge computing, can be adapted to CES/LSS contexts, which demand isolation, autonomy, and high reliability. Challenges related to model integration, simulation scalability, and the bidirectional transfer of technologies and modeling between Earth-based and space systems are discussed. This paper concludes with a SWOT analysis and a roadmap for future research. This work lays the foundation for developing sustainable, intelligent, and autonomous energy infrastructures—both terrestrial and extraterrestrial. Full article
(This article belongs to the Special Issue Advanced Smart Grid Technologies, Applications and Challenges)
24 pages, 4654 KiB  
Article
Drug Combination Recommendation Model for Systemic Lupus Erythematosus and Antiphospholipid Syndrome
by Ling Wang, Zhengyang Zhang, Ziheng Zhang, Tie Hua Zhou and Keun Ho Ryu
Pharmaceuticals 2025, 18(8), 1224; https://doi.org/10.3390/ph18081224 - 19 Aug 2025
Viewed by 276
Abstract
Background: Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) are two common autoimmune disorders for which the choice of drug regimen is clinically crucial. However, due to drug-drug interactions and individual differences, the therapeutic process faces greater risks. Methods: In this [...] Read more.
Background: Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) are two common autoimmune disorders for which the choice of drug regimen is clinically crucial. However, due to drug-drug interactions and individual differences, the therapeutic process faces greater risks. Methods: In this study, we propose a drug recommendation model that combines drug combination frequency, risk assessment, and genetic interaction information with the aim of providing personalized, low-risk treatment options for patients with lupus erythematosus and antiphospholipid syndrome. We extracted drug combination frequencies and drug-gene interaction information from data sources, such as the MIMIC-III clinical database, Drug Bank, and Gene Expression Omnibus. The model comprehensively evaluates the frequency of drug combinations, the risk level, and the gene interaction information through a greedy algorithm to recommend the optimal drug alternatives. Results: The experimental results show that the model is able to effectively reduce the potential risk between drugs while ensuring the drug treatment effect. In addition, the performance evaluation of the drug recommendation model shows that the model performs well under different drug combinations and clinical scenarios, and can provide clinicians with effective drug substitution suggestions. Conclusions: This study provides an important theoretical basis and technical support for advancing the realization of personalized therapy and precision medicine. Full article
(This article belongs to the Section Pharmacology)
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27 pages, 3962 KiB  
Article
Optimization of Conventional and Ultrasound-Assisted Extraction to Maximize Recovery of Total Phenolic Content and In Vitro Antioxidant Activity from Crataegus almaatensis Leaves
by Zhanar Nabiyeva, Akerke Kulaipbekova, Serena Carpentieri, Yuliya Pronina, Abdyssemat Samadun, Elmira Assembayeva and Giovanna Ferrari
Antioxidants 2025, 14(8), 1003; https://doi.org/10.3390/antiox14081003 - 16 Aug 2025
Viewed by 378
Abstract
Background: Crataegus almaatensis, an endemic hawthorn species from Kazakhstan, is known for its rich content of phenolic compounds and flavonoids with significant pharmacological potential. This study aimed to optimize and compare conventional solid–liquid extraction (SLE) and ultrasound-assisted extraction (UAE) processes for maximizing [...] Read more.
Background: Crataegus almaatensis, an endemic hawthorn species from Kazakhstan, is known for its rich content of phenolic compounds and flavonoids with significant pharmacological potential. This study aimed to optimize and compare conventional solid–liquid extraction (SLE) and ultrasound-assisted extraction (UAE) processes for maximizing the extractability of bioactive compounds from hawthorn leaves powder. Methods: The effects of temperature, extraction time, ethanol concentration, and solid-to-liquid ratio (or ultrasound power in the case of UAE) on total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity (FRAP, DPPH, and ABTS assays) were systematically evaluated. Results: The UAE method yielded higher concentrations of TPC and TFC, with up to 16% improvement in TPC and reduced ethanol usage (40% (v/v)) compared to SLE (75% (v/v)), demonstrating its efficiency and sustainability. Optimal extraction conditions were identified as 70 °C, 75% ethanol, 34 min, and an S/L ratio of 0.05 g/mL for SLE, 70 °C, 40% ethanol, 44 min, and 100 W US power for UAE. High-resolution HPLC-DAD and LC-Q/TOF-MS analyses confirmed the presence of key phenolic acids and flavonoid glycosides, including chlorogenic acid and apigenin-8-C-glucoside-2′-rhamnoside as the most abundant compounds identified. Conclusions: These findings validate UAE as an innovative, eco-friendly method for extracting bioactive compounds from hawthorn leaves and highlight its potential for developing natural antioxidants for pharmaceutical and nutraceutical applications. Full article
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22 pages, 2705 KiB  
Review
Autoantibodies in Systemic Lupus Erythematosus: Diagnostic and Pathogenic Insights
by Eleni Pagkopoulou, Charalampos Loutradis, Maria Papaioannou, Maria Daoudaki, Maria Stangou and Theodoros Dimitroulas
J. Clin. Med. 2025, 14(16), 5714; https://doi.org/10.3390/jcm14165714 - 12 Aug 2025
Viewed by 1627
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and the production of autoantibodies targeting nuclear, cytoplasmic, and cell surface antigens. These autoantibodies are central to disease pathogenesis, contribute to immune complex formation and organ damage, and serve [...] Read more.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and the production of autoantibodies targeting nuclear, cytoplasmic, and cell surface antigens. These autoantibodies are central to disease pathogenesis, contribute to immune complex formation and organ damage, and serve as essential diagnostic and prognostic markers. Their detection supports disease classification, guides clinical decision-making, and offers insight into disease activity and therapeutic response. Traditional markers such as anti-nuclear antibodies (ANA), anti-dsDNA, and anti-Sm antibodies remain diagnostic cornerstones, but growing attention is given to anti-C1q, anti-nucleosome antibodies (ANuA), anti-ribosomal P, antiphospholipid, and anti-cytokine antibodies due to their associations with specific disease phenotypes and activity. These markers may reflect disease activity, specific organ involvement, or predict flares. The mechanisms underlying their persistence include B cell tolerance failure and long-lived plasma cell activity. The aim of this review is to summarize current knowledge on the major autoantibodies in SLE, appraise available detection methods, highlight their clinical utility and limitations and present evidence on the association between antibodies and disease phenotypes. Full article
(This article belongs to the Section Immunology)
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29 pages, 912 KiB  
Review
Chimeric Antigen Receptor T Cell Immunotherapy for Autoimmune Rheumatic Disorders: Where Are We Now?
by Panagiota Anyfanti, Paschalis Evangelidis, Nikolaos Kotsiou, Anna Papakonstantinou, Ioannis Eftychidis, Ioanna Sakellari, Theodoros Dimitroulas and Eleni Gavriilaki
Cells 2025, 14(16), 1242; https://doi.org/10.3390/cells14161242 - 12 Aug 2025
Viewed by 666
Abstract
Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies’ management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T [...] Read more.
Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies’ management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T cell therapy can induce sustained remission by the elimination of autoreactive B cell populations resistant to the standard of care treatment options. Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), antiphospholipid syndrome (APS), and primary Sjögren’s syndrome (pSS). Treatment outcomes include reduced disease activity, normalization of serologic markers, improved organ function, and drug-free remission, even after B cell reconstitution. Additionally, toxicities, primarily limited to mild cytokine release syndrome (CRS), were generally manageable with supportive care. Encouraging preliminary results have led to the development of several ongoing clinical trials investigating CAR-T cell therapy across multiple ARDs and patient populations, including pediatric patients. This review summarizes the current clinical experience and provides a comprehensive overview of ongoing clinical trials exploring CAR-T cell immunotherapy for ARDs. Full article
(This article belongs to the Special Issue Genetic and Cellular Basis of Autoimmune Diseases)
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8 pages, 232 KiB  
Article
Inflamed Pathways to Motherhood: Evaluating Obstetric and Neonatal Outcomes in Rheumatic Pregnancies
by Batuhan Turgay, Uğurcan Zorlu, Bulut Varlı, Gülşah Aynaoğlu Yıldız, Şahin Kaan Baydemir, Cem Somer Atabekoğlu and Tahsin Murat Turgay
J. Clin. Med. 2025, 14(16), 5692; https://doi.org/10.3390/jcm14165692 - 12 Aug 2025
Viewed by 266
Abstract
Objective: This study aims to evaluate obstetric and neonatal outcomes in pregnancies complicated by RDs and to identify hemogram-derived biomarkers associated with adverse perinatal events. Methods: This retrospective cohort study analyzed 360 pregnancies in individuals diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus [...] Read more.
Objective: This study aims to evaluate obstetric and neonatal outcomes in pregnancies complicated by RDs and to identify hemogram-derived biomarkers associated with adverse perinatal events. Methods: This retrospective cohort study analyzed 360 pregnancies in individuals diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), Sjögren’s disease, sarcoidosis, undifferentiated connective tissue disease (UCTD), and other autoimmune conditions, followed up at the Department of Obstetrics and Gynecology, Ankara University Faculty of Medicine, between 2013 and 2018. Data on disease activity, maternal complications, neonatal outcomes, and inflammatory markers were extracted from electronic medical records. Results: Patients with SSc had the highest rates of preterm birth (57.1%) and fetal growth restriction (FGR) (42.9%), whereas those with SLE (50%) and AS (25%) exhibited the highest disease flare rates. Neonates born to mothers with SSc, SLE, and Sjögren’s disease had significantly lower Apgar scores, suggesting increased neonatal distress. NICU admission was associated with elevated neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR), with higher NLR and ELR also predicting spontaneous abortion. Monocyte-to-lymphocyte ratio (MLR) and ELR demonstrated the highest predictive value for composite adverse perinatal outcomes. Additionally, RA patients experiencing disease flares had an 87.5% cesarean section (CS) rate, significantly exceeding the general population rate. Conclusions: This study underscores the increased risk of preterm birth, FGR, and neonatal complications in RD pregnancies, particularly in SSc and SLE patients. The findings suggest that early risk assessment using hemogram-based inflammatory markers may improve perinatal management and patient stratification. Full article
(This article belongs to the Special Issue Recent Advances in Adverse Pregnancy and Neonatal Outcomes)
15 pages, 1128 KiB  
Article
Anifrolumab for Nonsystemic Cutaneous Lupus Erythematosus: Clinical Experience, Immunologic Insights, and Review of the Literature
by Javier Loricera, Carmen Bejerano, Andrea Estébanez, Irene García, Nasser Mohammad, Mireia Sanmartín, Marta González-Fernández, Iván Ferraz Amaro, Marcos A. González-López, Mayra V. García-Contreras, Marcos López-Hoyos and Ricardo Blanco
J. Clin. Med. 2025, 14(16), 5683; https://doi.org/10.3390/jcm14165683 - 11 Aug 2025
Viewed by 405
Abstract
Objective: Anifrolumab is approved for systemic lupus erythematosus (SLE). Its off-label use in non-systemic cutaneous lupus erythematosus (NSCLE) remains poorly characterized. We aimed to assess its effectiveness and safety in refractory NSCLE, supported by a literature review and exploratory immunologic analysis. Methods: This [...] Read more.
Objective: Anifrolumab is approved for systemic lupus erythematosus (SLE). Its off-label use in non-systemic cutaneous lupus erythematosus (NSCLE) remains poorly characterized. We aimed to assess its effectiveness and safety in refractory NSCLE, supported by a literature review and exploratory immunologic analysis. Methods: This multicenter observational study included patients with NSCLE treated with anifrolumab. Skin disease was assessed using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). CLASI scores at baseline were compared to months 1, 3, and 6. A narrative literature review was also conducted. In a subset of three patients, peripheral blood immunophenotyping was performed before and after treatment to explore immunologic surrogate markers associated with clinical response. Results: Fifteen patients (11 women; mean age 52.1 ± 11.7 years) were included. All had received topical corticosteroids and hydroxychloroquine. Most of them had failed multiple systemic therapies. Anifrolumab (300 mg IV every 4 weeks) was used in combination (n = 12) or as monotherapy (n = 3). All patients improved. Median CLASI-A decreased from 16 to 1 (p < 0.001); CLASI-D decreased from 5 to 4 (p < 0.001). The literature review identified 6 publications reporting 14 additional cases of NSCLE with similar outcomes and minimal adverse effects. Immunologic profiling pointed to an increase in intermediate and non-classical and decreased PD-1 expression in monocytes and NK cells after 12 weeks of treatment. Conclusions: Anifrolumab appears effective and relatively safe in refractory NSCLE. Preliminary immunologic data suggest changes in peripheral blood monocyte subsets and NK cells. However, these findings must be confirmed in prospective, controlled clinical trials. Full article
(This article belongs to the Section Dermatology)
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11 pages, 243 KiB  
Article
Characteristics of Systemic Lupus Erythematosus Patients with Diffuse Alveolar Hemorrhage: Clinical Features and Outcomes from a Single-Center Experience
by Radosław Dziedzic, Mariusz Korkosz and Joanna Kosałka-Węgiel
J. Clin. Med. 2025, 14(16), 5614; https://doi.org/10.3390/jcm14165614 - 8 Aug 2025
Viewed by 356
Abstract
Background/Objectives: Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication that might occur in the course of systemic lupus erythematosus (SLE), presenting with acute respiratory symptoms, a rapid drop in hemoglobin, and diffuse pulmonary infiltrates. Despite various studies, clinical and laboratory [...] Read more.
Background/Objectives: Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication that might occur in the course of systemic lupus erythematosus (SLE), presenting with acute respiratory symptoms, a rapid drop in hemoglobin, and diffuse pulmonary infiltrates. Despite various studies, clinical and laboratory risk factors for DAH in SLE remain unclear due to small cohort sizes and inconsistent findings. Methods: We analyzed the medical records of all adult SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022, to look for patients with DAH. Results: In a cohort of 1039 SLE patients, DAH was confirmed in five cases (0.48%), all presenting with respiratory symptoms and significant hemoglobin drops. No patients required intensive care unit admission or mechanical ventilation, and all survived the 5-year follow-up after receiving immunosuppressive therapy including glucocorticosteroids and cyclophosphamide, and also rituximab in one case. Common features included constitutional symptoms, hematologic and renal involvement, and frequent presence of antiphospholipid antibodies, with antiphospholipid syndrome diagnosed in three patients (60%). All patients had positive antinuclear antibodies, with the presence of anti-dsDNA and anti-SSA antibodies, each present in 3 out of 5 cases. Conclusions: In conclusion, early recognition and aggressive treatment of DAH in SLE patients, who often present other medical comorbidities as hematological, renal, and cardiovascular manifestations, is critical for improving long-term outcomes. Full article
(This article belongs to the Section Immunology)
56 pages, 1035 KiB  
Review
Trace Elements—Role in Joint Function and Impact on Joint Diseases
by Łukasz Bryliński, Katarzyna Brylińska, Filip Woliński, Jolanta Sado, Miłosz Smyk, Olga Komar, Robert Karpiński, Marcin Prządka and Jacek Baj
Int. J. Mol. Sci. 2025, 26(15), 7493; https://doi.org/10.3390/ijms26157493 - 2 Aug 2025
Viewed by 775
Abstract
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a [...] Read more.
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article
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24 pages, 936 KiB  
Article
Anti-Ku Antibodies: Clinical Associations, Organ Damage, and Prognostic Implications in Connective Tissue Diseases
by Céline La, Julie Smet, Carole Nagant and Muhammad Soyfoo
Int. J. Mol. Sci. 2025, 26(15), 7433; https://doi.org/10.3390/ijms26157433 - 1 Aug 2025
Viewed by 397
Abstract
Anti-Ku antibodies are rare autoantibodies associated with connective tissue diseases (CTDs), but their clinical significance remains poorly understood due to limited studies. Semi-quantitative immunodot assays yield positive, negative, or borderline results, with the clinical relevance of borderline findings remaining unclear. The purpose of [...] Read more.
Anti-Ku antibodies are rare autoantibodies associated with connective tissue diseases (CTDs), but their clinical significance remains poorly understood due to limited studies. Semi-quantitative immunodot assays yield positive, negative, or borderline results, with the clinical relevance of borderline findings remaining unclear. The purpose of this study is to characterize the clinical spectrum of anti-Ku-positive patients and evaluate the clinical significance of anti-Ku-borderline results in CTD management. A retrospective cohort study was conducted at Hôpital Erasme, including all patients with anti-Ku-positive or borderline results, over a 10-year period. Clinical and biological data were collected from medical records and analyzed for disease associations, organ involvement, and outcomes. Among 47 anti-Ku-positive patients, systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) were the most common diagnoses. Interstitial lung disease (ILD) occurred in 23.4% and renal involvement in 12.8% of patients. Cytopenia was significantly associated with glomerulonephritis. Organ damage, particularly pulmonary and renal involvement, correlated with increased mortality. In the borderline group (n = 33), SLE and SS remained the predominant diagnoses. During follow-up, three patients died (all with isolated ILD without associated CTD), one required chronic dialysis, and one underwent lung transplantation. ILD was present in 7/22 (31.8%) borderline patients, and renal involvement in 7/32 (21.9%). This study demonstrates significant associations between anti-Ku antibodies and organ damage, with increased mortality risk. The high prevalence of pulmonary and renal involvement in anti-Ku-borderline patients suggests that these results carry substantial clinical significance and should prompt comprehensive CTD evaluation. These findings support treating borderline anti-Ku results with the same clinical vigilance as positive results, given their similar association with severe organ involvement and adverse outcomes. Full article
(This article belongs to the Section Molecular Immunology)
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10 pages, 1604 KiB  
Article
Anifrolumab Attenuates Follicular Helper T Cell Activation in Patients with Systemic Lupus Erythematosus
by Ádám Diós, Ágnes Gyetvai, Gábor Papp and Tünde Tarr
Int. J. Mol. Sci. 2025, 26(15), 7397; https://doi.org/10.3390/ijms26157397 - 31 Jul 2025
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Abstract
Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects [...] Read more.
Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects of inhibited type I IFN signaling on circulating follicular helper T subsets (TFH), follicular regulatory T cells (TFR), and B lymphocyte subpopulations, reflecting the ongoing germinal center reactions in SLE patients. Peripheral blood samples were obtained from ten SLE patients before the initiation of anifrolumab treatment, and at months 6 and 12 of the intervention period. Flow cytometry analysis was performed to assess the frequencies of circulating TFH cell subsets, TFR cells, and certain B cell subpopulations. Serological parameters, including autoantibody levels and complement components, were determined as part of the routine diagnostic evaluation. We observed a significant and sustained reduction in the percentage of activated circulating TFH cells. Notably, the frequency of CXCR3CCR6+ TFH17 cells decreased, whereas the proportion of CXCR3+CCR6 TFH1 cells increased significantly. Furthermore, the proportion of the IgDCD27 double-negative B lymphocytes was also significantly reduced. These findings suggest that anifrolumab therapy attenuates TFH cell activation, which may contribute to its clinical efficacy by modulating germinal center responses in SLE. Full article
(This article belongs to the Special Issue Drug Therapy of Systemic Lupus Erythematosus)
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