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Search Results (1,144)

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Keywords = systemic lupus erythematosus

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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
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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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 1268
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 548
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 245
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 293
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 312
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)
9 pages, 680 KiB  
Case Report
Borderline Oxacillin-Resistant Staphylococcus aureus (BORSA) Bacteremia—Case Report
by Beverly Buffart, Philippe Clevenbergh, Alina Stiuliuc, Ioannis Raftakis, Mony Hing, Véronique Yvette Miendje Deyi, Olivier Denis, Delphine Martiny and Nicolas Yin
Antibiotics 2025, 14(8), 809; https://doi.org/10.3390/antibiotics14080809 - 7 Aug 2025
Viewed by 416
Abstract
Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In [...] Read more.
Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In this report, we present a rare case of BORSA bacteremia and discuss potential approaches to improve its detection and management. Case presentation: A 39-year-old woman with systemic lupus erythematosus was admitted for a suspected exacerbation, complicated by multiple serositis and nephritis. She was on chronic treatment with methylprednisolone and hydroxychloroquine. On admission, she was afebrile. Laboratory investigations revealed elevated C-reactive protein and increased D-dimer levels. Later, she developed a septic peripheral venous thrombophlebitis, and treatment was adjusted to amoxicillin–clavulanate. Blood cultures grew S. aureus, prompting a switch to intravenous oxacillin based on a negative penicillin-binding protein 2a test. A discrepancy in the antimicrobial susceptibility test was observed, with cefoxitin showing susceptibility and oxacillin resistance. Further characterizations were carried out, confirming a BORSA infection. Treatment was switched to linezolid and ciprofloxacin with good recovery. Conclusions: This case highlights the complexity of managing a patient with an uncommon and poorly documented infection. The lack of data on BORSA infections and the difficulties in detecting and treating them led to a prolonged delay in the appropriate management of this patient. Full article
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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 695
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 345
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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16 pages, 1212 KiB  
Review
The Sleep–Skin Axis: Clinical Insights and Therapeutic Approaches for Inflammatory Dermatologic Conditions
by Alana Sadur, Lucie Joerg, Amelia Stapleton Van Doren, Ellen T. Lee, Dia Shah, Aniket K. Asees and Sonal Choudhary
Dermato 2025, 5(3), 13; https://doi.org/10.3390/dermato5030013 - 31 Jul 2025
Viewed by 589
Abstract
Sleep is crucial to overall health and plays a significant role in skin function. While the circadian rhythm has been extensively researched for its impact on the body’s optimal functioning, the skin also possesses an independent circadian system that serves many important functions. [...] Read more.
Sleep is crucial to overall health and plays a significant role in skin function. While the circadian rhythm has been extensively researched for its impact on the body’s optimal functioning, the skin also possesses an independent circadian system that serves many important functions. Sleep disruptions or deprivation can significantly affect skin conditions, by compromising the skin barrier and impairing processes such as collagen production, cellular repair, and wound healing. Given the commonality of sleep disturbances, it is crucial to understand the connection between sleep, circadian regulation, and skin health. This is particularly important in understudied populations, such as those with occupational sleep disruption and individuals with hormone-related conditions like PCOS and menopause. Bidirectional relationships have been established between sleep and several inflammatory skin conditions, including atopic dermatitis, psoriasis, rosacea, and hidradenitis suppurativa. While acne is influenced by sleep, the reverse relationship, how acne affects sleep quality, has not been well established. Chronic sleep disruption can increase cortisol levels and oxidative stress, both of which contribute to skin aging and the progression of autoimmune skin conditions, including systemic lupus erythematosus. As sleep is a modifiable risk factor, it is crucial to consider therapeutic options and interventions to prevent or alleviate skin conditions. This review discusses various therapeutic approaches, including melatonin, L-Theanine, Magnesium-L-threonate, Inositol, Cinnamomi cortex, nervous system regulation, and proper sleep hygiene. These therapeutic options have been studied for their impact on sleep, and importantly, several have been evaluated for their utility as adjuncts for treating skin conditions. Overall, the relationship between sleep and skin health is clear, and incorporating sleep-focused therapeutic interventions offers potential to improve both sleep quality and skin health in individuals with a variety of skin conditions. Full article
(This article belongs to the Special Issue Reviews in Dermatology: Current Advances and Future Directions)
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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
Viewed by 493
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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18 pages, 955 KiB  
Article
Unequal Burdens: Exploring Racial Disparities in Cardiovascular and SLE Outcomes Using National Inpatient Database 2016–2021
by Freya Shah, Siddharth Pravin Agrawal, Darshilkumar Maheta, Jatin Thukral and Syeda Sayeed
Rheumato 2025, 5(3), 10; https://doi.org/10.3390/rheumato5030010 - 30 Jul 2025
Viewed by 411
Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study [...] Read more.
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study examines racial and ethnic disparities in cardiovascular outcomes among hospitalized SLE patients in the United States. Methods: This retrospective study utilized the National Inpatient Sample (NIS) database from 2016 to 2021 to analyze hospitalizations of adult patients (≥18 years) with a primary or secondary diagnosis of SLE. Patients were stratified into racial/ethnic groups: White, Black, Hispanic, Asian, Native American, and Other. Primary outcomes include major adverse cardiovascular events (MACEs), which are a composite of in-hospital mortality, myocardial infarction (MI), sudden cardiac death, and other SLE-related outcomes including cardiac, pulmonary, and renal involvement. Statistical analyses included multivariable logistic regression models adjusted for demographic, socioeconomic, and hospital-related factors to assess racial disparities. Results: The study included 514,750 White, 321,395 Black, and 146,600 Hispanic patients, with smaller proportions of Asian, Native American, and Other racial groups. Black patients had significantly higher odds of in-hospital mortality (OR = 1.17, 95% CI = 1.08–1.26, p < 0.001) and sudden cardiac death (OR = 1.64, 95% CI = 1.46–1.85, p < 0.001) compared to White patients. Asian patients also exhibited increased mortality risk (OR = 1.37, 95% CI = 1.14–1.63, p = 0.001) as compared to Whites. Conversely, Black (OR = 0.90, 95% CI = 0.85–0.96, p = 0.01) and Hispanic (OR = 0.87, 95% CI = 0.80–0.96, p = 0.03) patients had lower odds of MI. Racial disparities in access to care, socioeconomic status, and comorbidity burden may contribute to these differences. Conclusion: Significant racial and ethnic disparities exist in cardiovascular outcomes among hospitalized SLE patients. Black and Asian individuals face higher in-hospital all-causes mortality and sudden cardiac death risks, while Black and Hispanic patients exhibit lower MI rates. Addressing social determinants of health, improving access to specialized care, and implementing targeted interventions may reduce disparities and improve outcomes in minority populations with SLE. Full article
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25 pages, 2913 KiB  
Review
The Art of Interpreting Antinuclear Antibodies (ANAs) in Everyday Practice
by Marcelina Kądziela, Aleksandra Fijałkowska, Marzena Kraska-Gacka and Anna Woźniacka
J. Clin. Med. 2025, 14(15), 5322; https://doi.org/10.3390/jcm14155322 - 28 Jul 2025
Viewed by 554
Abstract
Background: Antinuclear antibodies (ANAs) serve as crucial biomarkers for diagnosing systemic autoimmune diseases; however, their interpretation can be complex and may not always correlate with clinical symptoms. Methods: A comprehensive narrative review was conducted to evaluate the peer-reviewed literature published between 1961 and [...] Read more.
Background: Antinuclear antibodies (ANAs) serve as crucial biomarkers for diagnosing systemic autoimmune diseases; however, their interpretation can be complex and may not always correlate with clinical symptoms. Methods: A comprehensive narrative review was conducted to evaluate the peer-reviewed literature published between 1961 and 2025. Databases, including PubMed and Scopus, were searched using combinations of controlled vocabulary and free-text terms relating to antinuclear antibodies and their clinical significance. The objective was to gather and synthesize information regarding the diagnostic utility and interpretation of ANA testing in routine medical practice. Discussion: The indirect immunofluorescence assay (IIF) on HEp-2 cells is established as the gold standard for detecting ANAs, facilitating the classification of various fluorescent patterns. While a positive ANA test can suggest autoimmune disorders, the presence and titre must be interpreted alongside clinical findings, as low titres often lack diagnostic significance. Findings indicate that titres higher than 1:160 may provide greater specificity in differentiating true positives from false positives in healthy individuals. The study also emphasizes the relevance of fluorescence patterns, with specific patterns linked to particular diseases, although many do not have strong clinical correlations. Moreover, certain autoantibodies demonstrate high specificity for diseases like systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Ultimately, while ANA testing is invaluable for diagnosing connective tissue diseases, healthcare providers must consider its limitations to avoid misdiagnosis and unnecessary treatment. Conclusions: ANA testing is a valuable tool in the diagnosis of connective tissue diseases, but its interpretation must be approached with caution. Clinical context remains crucial when evaluating ANA results to avoid misdiagnosis and overtreatment. This review is about the diagnostic aspects and clinical consequences of ANA testing, as well as highlighting both the diagnostic benefits and the potential limitations of this procedure in everyday clinical practice. The review fills a gap in the literature by integrating the diagnostic and clinical aspects of ANA testing, with a focus on real-world interpretation challenges. Full article
(This article belongs to the Section Immunology)
22 pages, 11171 KiB  
Article
Artesunate Ameliorates SLE Atherosclerosis Through PPARγ-Driven Cholesterol Efflux Restoration and Disruption of Lipid Raft-Organized TLR9/MyD88 Signaling Pathway
by Miao Zhang, Xinyu Pan, Yuanfang He, Kairong Sun, Zhiyu Wang, Weiyu Tian, Haonan Qiu, Yiqi Wang, Chengping Wen and Juan Chen
Biomolecules 2025, 15(8), 1078; https://doi.org/10.3390/biom15081078 - 25 Jul 2025
Viewed by 375
Abstract
Systemic lupus erythematosus (SLE) is characterized by autoimmune dysregulation, elevated autoantibody production, and persistent inflammation, predisposing patients to atherosclerosis (AS). Atherogenesis is dependent on lipid homeostasis and inflammatory processes, with the formation of lipid-laden, macrophage-derived foam cells (MDFC) essential for atherosclerotic lesion progression. [...] Read more.
Systemic lupus erythematosus (SLE) is characterized by autoimmune dysregulation, elevated autoantibody production, and persistent inflammation, predisposing patients to atherosclerosis (AS). Atherogenesis is dependent on lipid homeostasis and inflammatory processes, with the formation of lipid-laden, macrophage-derived foam cells (MDFC) essential for atherosclerotic lesion progression. Elevated cholesterol levels within lipid rafts trigger heightened pro-inflammatory responses in macrophages via Toll-like receptor 9 (TLR9). Artesunate (ART), an artemisinin derivative sourced from Artemisia annua, exhibits therapeutic potential in modulating inflammation and autoimmune conditions. Nonetheless, its impact and mechanisms in SLE-associated AS (SLE-AS) remain largely unexplored. Our investigation demonstrated that ART could effectively ameliorate lupus-like symptoms and atherosclerotic plaque development in SLE-AS mice. Moreover, ART enhanced cholesterol efflux from MDFC by upregulating ABCA1, ABCG1, and SR-B1 both in vivo and in vitro. Moreover, ART reduced cholesterol accumulation in bone marrow-derived macrophages (BMDMs), thereby diminishing TLR9 recruitment to lipid rafts. ART also suppressed TLR9 expression and its downstream effectors in the kidney and aorta of SLE-AS mice, attenuating the TLR9-mediated inflammatory cascade in CPG2395 (ODN2395)-stimulated macrophages. Through bioinformatics analysis and experimental validation, PPARγ was identified as a pivotal downstream mediator of ART in macrophages. Depleting PPARγ levels reduced the expression of ABCA1, ABCG1, and SR-B1 in macrophages, consequently impeding cholesterol efflux. In conclusion, these findings suggest that ART ameliorates SLE-AS by restoring cholesterol homeostasis through the PPARγ-ABCA1/ABCG1/SR-B1 pathway and suppressing lipid raft-driven TLR9/MyD88 inflammation. Full article
(This article belongs to the Section Lipids)
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47 pages, 4589 KiB  
Review
Understanding Sex Differences in Autoimmune Diseases: Immunologic Mechanisms
by Yu Rin Kim, YunJae Jung, Insug Kang and Eui-Ju Yeo
Int. J. Mol. Sci. 2025, 26(15), 7101; https://doi.org/10.3390/ijms26157101 - 23 Jul 2025
Viewed by 701
Abstract
Autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome show pronounced sex disparities in prevalence, severity, and clinical outcomes, with females disproportionately affected. Emerging evidence highlights sex-based differences in immune and inflammatory responses as key contributors to this bias. Genetic factors—including sex [...] Read more.
Autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome show pronounced sex disparities in prevalence, severity, and clinical outcomes, with females disproportionately affected. Emerging evidence highlights sex-based differences in immune and inflammatory responses as key contributors to this bias. Genetic factors—including sex chromosomes, skewed X chromosome inactivation, and sex-biased microRNAs—as well as sex hormones and pregnancy modulate gene expression and immune cell function in a sex-specific manner. Additionally, sex hormone-dependent epigenetic modifications influence the transcription of critical immune regulators. These genetic and hormonal factors collectively shape the activation, differentiation, and effector functions of diverse immune cell types. Environmental factors—including infections, gut microbiota, environmental chemicals and pollutants, and lifestyle behaviors such as diet, smoking, UV exposure, alcohol and caffeine intake, physical activity, and circadian rhythms—further modulate immune function and autoimmune disease pathogenesis in a sex-dependent manner. Together, these mechanisms contribute to the heightened risk and distinct clinical features of autoimmunity in females. A deeper understanding of sex-biased immune regulation will facilitate the identification of novel biomarkers, enable patient stratification, and inform the development of sex-specific diagnostic and therapeutic strategies for autoimmune diseases. Full article
(This article belongs to the Section Molecular Immunology)
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