Search Results (1,365)

Background/Objectives: Interleukin-6 (IL-6) is a pro-inflammatory cytokine implicated in the pathogenesis of SLE. Beyond its role in disease activity, IL-6 has also been associated with increased cardiovascular risk, potentially promoting endothelial dysfunction, atherosclerosis, and thromboinflammation. Our study aimed to investigate the associations between IL-6 levels, disease manifestations, organ damage, cardiovascular comorbidities, and treatment regimens in a cohort of SLE patients. Methods: A total of 88 SLE patients were recruited from the Rheumatology Clinic of the Clinical Rehabilitation Hospital, Iași. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI) and irreversible organ damage with the SLICC/ACR Damage Index. Serum IL-6 levels were measured by ELISA. Statistical analyses included Mann–Whitney U tests and Spearman correlation coefficients. Results: Among 88 SLE patients (89.8% female, mean age 51.9 ± 14.8 years), 68.2% presented irreversible organ damage, most frequently cardiovascular (26.1%). Regarding disease manifestations, IL-6 was non-significantly elevated in patients with arthritis, rash, and low complement levels. Serum concentrations also tended to increase with disease severity, being higher in severe compared to moderate activity, and in moderate versus mild activity. Significant associations were found between IL-6 and hypertension (p = 0.027), aortic atherosclerosis (p = 0.034), menopausal status (p = 0.015), and hypercholesterolemia (p = 0.034). No significant differences were observed across treatment subgroups. Conclusions: IL-6 showed limited correlation with SLE clinical activity but was significantly elevated in patients with selected cardiovascular comorbidities. These findings suggest a potential contribution of IL-6 to cardiovascular risk in SLE, warranting further investigation in larger cohorts. Full article

Accurate assessment of appendicular lean mass (ALM), an essential component for evaluating sarcopenia and nutritional status, typically requires dual-energy X-ray absorptiometry (DXA); however, its widespread clinical application is limited by cost and accessibility. This study aimed to develop a simple anthropometry-based equation for estimating ALM in women with systemic lupus erythematosus (SLE) and to compare its predictive performance with existing models. This cross-sectional study included 92 female patients with SLE. A multiple regression model was developed, incorporating height, body weight, calf circumference (CC), and age. Model performance was internally validated using five-fold cross-validation, and agreement with DXA-measured ALM was assessed using out-of-fold predictions. The diagnostic performance for detecting low skeletal muscle mass index (SMI) was also evaluated and compared with previously published equations (Hwang and Santos). The predicted ALM showed good correlation with measured ALM (R² = 0.76) and moderate agreement (Lin’s concordance correlation coefficient [CCC] = 0.829), with a root mean square error of 1.38 kg. Sensitivity and specificity for detecting low SMI were 65.0% and 88.9%, respectively. The proposed equation demonstrated comparable or superior performance (CCC: Hwang 0.782; Santos 0.672) and may serve as a practical tool for estimating ALM in female patients with SLE. Full article

Background: Vitamin D is involved not only in calcium–phosphate homeostasis but also in immune and endothelial regulation. Vitamin D deficiency has been suggested to worsen disease activity in systemic lupus erythematosus (SLE). Environmental and lifestyle factors, including seasonal sun exposure, smoking, diet, and supplementation, may influence vitamin D status and disease manifestations. This study aimed to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels, disease activity, and anti-double-stranded DNA (anti-dsDNA) antibody titers in patients with SLE, taking selected lifestyle and environmental factors into account. Methods: Serum 25(OH)D concentrations, SLE disease activity assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and anti-dsDNA antibody titers were measured in patients with SLE and healthy controls. Blood samples were collected during sunny (April–September) and non-sunny (October–March) months. Information on vitamin D supplementation, smoking status, and dietary habits was obtained using a structured questionnaire. Associations between vitamin D status, disease activity, anti-dsDNA seropositivity, season of blood collection, supplementation, smoking, and diet were analyzed statistically. Results: Patients with SLE had significantly higher mean serum 25(OH)D levels than controls, mainly due to frequent vitamin D supplementation. No significant associations were observed between serum 25(OH)D levels and SLEDAI-2K scores or anti-dsDNA antibody positivity. Seasonality, smoking status, and adherence to special diets were not significantly related to disease activity or anti-dsDNA seropositivity. Vitamin D supplementation was strongly associated with sufficient 25(OH)D levels but did not translate into reduced disease activity or lower anti-dsDNA prevalence. Conclusions: Serum 25(OH)D concentration was not associated with clinical or immunological activity of SLE in this cross-sectional study, despite effective correction of deficiency through supplementation. These findings likely reflect the heterogeneity of SLE and the limitations of single time-point assessments, although regular monitoring and individualized vitamin D supplementation may still be considered in SLE care, particularly in the context of recommended photoprotection. Full article

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with extraintestinal manifestations, including primary sclerosing cholangitis (PSC). Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that rarely coexists with UC or PSC. The concurrent occurrence of UC, PSC, and SLE in a single individual represents a unique diagnostic and therapeutic challenge. Vedolizumab, a gut-selective biologic agent, is effective for managing UC; however, its utility in patients presenting with this triad of conditions has not yet been explored. Case summary: A 32-year-old man presented with a 10-year history of recurrent upper abdominal pain, frequently accompanied by high-grade fever, along with recent onset of jaundice, diarrhea, hematochezia, and chronic rashes. Diagnostic evaluation confirmed PSC, SLE, and severe UC. During hospitalization, the patient also developed bacteremia. Initial management of UC with mesalazine and immunosuppressants (azathioprine followed by cyclosporine) resulted in limited clinical improvement. Vedolizumab was subsequently initiated, resulting in marked clinical improvements and near-complete endoscopic remission of UC. PSC and SLE remained clinically stable with ongoing therapies; however, the patient is currently awaiting liver transplantation for PSC. Conclusions: This case highlights the potential utility of vedolizumab in the treatment of UC in patients with concurrent PSC and SLE. Full article

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease characterized by multisystem involvement and substantial morbidity. Although survival has improved over recent decades, disease burden remains considerable due to cumulative organ damage, comorbidities, and treatment-related toxicity, particularly from long-term glucocorticoid use. Advances in the understanding of SLE immunopathogenesis have led to the development of targeted therapies. Currently approved agents include belimumab and anifrolumab, while obinutuzumab has been approved for lupus nephritis and has also demonstrated significant efficacy in phase III trials in SLE. Several additional agents are in late-stage clinical development, including litifilimab (targeting plasmacytoid dendritic cells), telitacicept and ianalumab (BAFF/APRIL and B-cell modulation), dapirolizumab pegol (CD40L blockade), deucravacitinib and upadacitinib (TYK2/JAK inhibition), and cenerimod (S1P1₁ modulation). This narrative review summarizes current phase III evidence and emerging therapeutic strategies, highlighting the ongoing transition toward precision medicine and individualized treatment approaches in SLE. Full article

Background: Pericardial involvement is the most common cardiac manifestation of systemic lupus erythematosus (SLE), ranging from mild effusion to recurrent pericarditis and cardiac tamponade. The influence of antiphospholipid syndrome (APS) on lupus-related pericardial disease remains unclear. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO. PubMed, Web of Science, Scopus, and the Cochrane Library were searched from inception to January 2026 for observational studies evaluating pericardial manifestations in adult SLE patients. APS/aPL status was considered a potential modifying factor when reported. Results: Seven observational studies were included. Pericardial involvement ranged from acute and recurrent pericarditis to large effusions and cardiac tamponade. Across studies, it was consistently associated with higher disease activity and markers of immune activation. Recurrent pericarditis emerged as a clinically relevant phenotype linked to more severe disease and worse outcomes. Cardiac tamponade, although rare, was associated with significant morbidity and mortality. APS/aPL-related data were heterogeneous and inconsistently reported across studies. No consistent APS-specific association with pericardial disease could be established, although APS or aPL-related findings were occasionally reported in selected severe or clinically complex presentations. Conclusions: Pericardial involvement in SLE reflects systemic inflammatory burden and spans a broad clinical spectrum. Current evidence regarding APS remains limited and heterogeneous, although APS may contribute to disease complexity in selected severe presentations. Importantly, isolated aPL positivity should not be interpreted as equivalent to formally classified APS. Prospective studies with standardized definitions and systematic assessment of APS are needed. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is characterized by diverse clinical presentations and complex immunological mechanisms. This study aimed to characterize patient serology associated with disease activity scored using the systemic lupus erythematosus disease activity index (SLEDAI) and investigate the molecular signature of complement activation (measured through C3dg, a complement breakdown product) in SLE patients utilizing high-throughput mass spectrometry and autoantibody profiling. Methods: Plasma samples from 39 SLE patients in four mutually exclusive groups based on either disease activity scores (high/low SLEDAI) or complement activation levels (high/low C3dg) were analyzed using rapid LC-MS/MS, followed by unsupervised and supervised protein expression analysis. Complement activation was evaluated by measuring C3dg levels, and disease activity was scored using SLEDAI. Autoantibody reactivities were profiled using global autoantibody protein microarrays. Data are available via ProteomeXchange with identifier PXD066214. Results: Differential proteomic analyses revealed 25 proteins associated with SLE disease activity (high vs. low SLEDAI scores) and 25 proteins linked to complement activation levels (high vs. low C3dg). Enriched pathways indicated that adaptive immune response, classical complement activation, and immunoglobulin production correlated with disease activity, while complement activation and coagulation cascades were primarily associated with complement activation levels. Autoantibody profiling highlighted distinct reactivity patterns between subgroups, suggesting varying degrees of immune-mediated tissue damage. Conclusions: In this study, disease activity and complement activation markers were associated with overlapping yet non-identical plasma proteomic patterns in SLE. These findings support the feasibility of rapid mass spectrometry-based proteomics and autoantibody profiling for generating candidate molecular signatures in SLE. These findings serve as exploratory signatures that require validation in larger independent cohorts before they can be considered for clinical stratification and decision-making. Full article

Objective: To evaluate the association of routine complete blood count (CBC)-derived inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI), with disease activity and exploratory neuropsychiatric risk stratification in patients with systemic lupus erythematosus (SLE). Methods: In this multi-center retrospective study, 579 SLE patients and 282 healthy controls (HCs) were recruited from five clinical centers between 2018 and 2025. NLR, MLR, PLR, and SIRI were calculated from routine CBC parameters. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), with high activity defined as SLEDAI-2K ≥ 10. The comparison between SLE patients and HCs was performed as an exploratory descriptive analysis to characterize systemic inflammatory profiles, whereas the primary analyses focused on associations with disease activity and NPSLE-related risk stratification. Results: SLE patients exhibited significantly higher levels of SIRI, NLR, PLR, and MLR compared to HCs (all p < 0.001). In this exploratory comparison, MLR showed the largest area under the curve for distinguishing SLE patients from HCs (AUC: 0.849, Cut-off: 0.263). In regression analyses, MLR, NLR, PLR, and SIRI were positively associated with SLEDAI-2K score. In multivariable linear regression analysis, MLR was associated with a higher SLEDAI-2K score (B = 4.600, 95% CI: 2.039–7.160, p < 0.001). In patients with available neuropsychiatric data, MLR, NLR, and SIRI were higher in patients with NPSLE than in those with non-NPSLE, whereas PLR showed no significant difference. SIRI showed modest exploratory discriminatory ability for NPSLE and may provide auxiliary information for NPSLE risk stratification (AUC: 0.710, p < 0.001, Cut-off: 1.438). Conclusions: Routine CBC-derived inflammatory biomarkers, particularly MLR, NLR, and SIRI, are associated with SLE disease activity and may serve as accessible, low-cost adjunctive tools for rapid clinical assessment. SIRI may provide additional auxiliary information for identifying patients at higher risk of neuropsychiatric involvement. However, these biomarkers should be interpreted as complementary screening or risk-stratification tools rather than substitutes for established disease activity indices or organ-specific evaluations. Further prospective studies are warranted to validate their clinical utility. Full article

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article

Type I interferons (IFN-I), including IFN-α, IFN-β, and IFN-ω, are central to antiviral defence and immune regulation. Autoantibodies targeting IFN-I (anti-IFN-I AAbs) have emerged as key pathogenic factors in severe coronavirus disease 2019 (COVID-19) and are detectable in systemic lupus erythematosus (SLE), a prototypic IFN-driven autoimmune disease. Here we compare the prevalence and clinical impact of anti-IFN-I autoantibodies (Aabs) in COVID-19 and SLE based on a structured review of 53 studies from 2014 to 2025 and highlight the clinical associations and therapeutic opportunities presented by these autoantibodies. In COVID-19, neutralising anti-IFN-α and/or anti-IFN-ω AAbs were consistently associated with severe disease and impaired antiviral responses, particularly in older male populations. In SLE, anti-IFN-α AAbs were variably detected; neutralising antibodies were associated with reduced interferon gene signatures in some cohorts but inconsistent correlations with disease activity. Therapeutically, anti-IFN-I AAbs in COVID-19 may inform risk stratification and early antiviral strategies, whereas in SLE, IFN-α blockade, including IFN-α kinoid vaccination, demonstrates modulation of IFN signatures but variable clinical benefit. Notably, these findings reveal an immunological paradox: the same neutralising mechanism that impairs antiviral defence in COVID-19 may attenuate chronic IFN-driven inflammation in SLE. Taken together, anti-IFN-I AAbs exert context-dependent effects: pathogenic in acute viral infection yet potentially modulatory in chronic IFN-driven autoimmunity. Prospective longitudinal studies are required to further clarify their translational utility and long-term clinical impact. Full article

Background: Hydroxychloroquine (HCQ) is widely used in systemic lupus erythematosus (SLE), yet cumulative exposure may result in progressive retinal toxicity. Structural biomarkers capable of identifying subclinical damage remain incompletely defined. Methods: In this cross-sectional controlled study, 60 female SLE patients receiving HCQ for ≥5 years (22 with clinically detectable maculopathy and 38 without) and 30 healthy controls underwent a comprehensive ophthalmologic assessment including spectral-domain optical coherence tomography (SD-OCT). Peripapillary retinal nerve fiber layer (RNFL) and macular thickness parameters were analyzed. Logistic regression and ROC analysis evaluated exposure-related risk. Results: Patients with clinically detectable maculopathy demonstrated significant superior and temporal RNFL thinning compared with patients with clinically undetectable maculopathy and controls (p ≤ 0.021). Inferior quadrant thinning was detectable in patients without ophthalmoscopic changes, suggesting subclinical neuroaxonal involvement. Parafoveal macular thinning was observed exclusively in the clinically detectable maculopathy group (p = 0.041). Cumulative dose >1000 g independently predicted toxicity (OR 3.84; 95% CI 1.72–8.56). The combined structural–exposure model demonstrated strong discrimination (AUC 0.89). Conclusions: HCQ-related retinal structural changes may be detectable on OCT in the absence of clinically apparent retinal findings. Our results support the concept of a dose-associated structural continuum in HCQ-related retinal injury, involving both inner retinal neuroaxonal parameters and parafoveal macular alterations. However, the cross-sectional design does not allow determination of the temporal sequence of inner versus outer retinal changes. Further longitudinal studies with combined inner and outer retinal layer-specific analysis are required before these findings can inform modifications to current screening strategies. Full article

Background/Objectives: Leukocyte telomere length (TL) is a marker of biological aging associated with cardiovascular disease, chronic kidney disease, and malignancy in the general population. Its long-term prognostic significance in systemic lupus erythematosus (SLE) remains unclear. We aimed to evaluate the association between baseline TL and long-term clinical outcomes in patients with SLE. Methods: Prospective cohort study including 97 Caucasian women with SLE. Relative TL was measured in whole blood using quantitative polymerase chain reaction (qPCR) at baseline. A control group of 50 healthy Caucasian women from the same geographical region was included for comparison. Patients were followed for a mean of 9.7 ± 2.8 years. Outcomes included thrombotic cardiovascular events, damage accrual, incident malignancy, and chronic kidney disease. Associations were assessed using multivariable regression models adjusted for potential confounders. Results: Mean age was 51.6 ± 13.8 years and mean relative TL was 4.3 ± 1.0. Relative TL was inversely associated with age (β = −0.20, p = 0.048) and was shorter in patients with hematological manifestations (p = 0.038). No differences in relative TL were observed between SLE patients and controls. Relative TL was not associated with disease activity, cumulative damage, cardiovascular risk factors, vitamin D levels, or subclinical atherosclerosis. During follow-up, 13.4% of patients experienced cardiovascular events, 10.3% developed malignancy, and 11.3% developed chronic kidney disease. Relative TL was initially associated with long-term damage accrual, glomerular filtration rate and cardiovascular events; however, after adjustment for age, only the association with glomerular filtration rate remained at the limit of statistical significance (p = 0.05). Conclusions: In this prospective cohort, relative TL was primarily associated with aging, hematological manifestations, and glomerular filtration rate, but not with disease activity or most long-term clinical outcomes. These findings suggest that TL reflects biological aging rather than disease-specific processes and has limited utility as a prognostic biomarker in SLE. Full article

Background: Systemic lupus erythematosus (SLE) is associated with an increased burden of cardiovascular disease (CVD), driven by dyslipidemia, hypertension, obesity, inflammation, and treatment. These factors can impact patient quality of life (QoL) by limiting physical activity. Objectives: To characterize lipid abnormalities as CVD risk factors in a Saudi SLE cohort and assess associations between lipid profile, SLE features, treatment, and patient-reported outcomes of physical activity. Methods: A cohort of adult SLE patients followed at King Saud University Medical City since 2021 was analyzed. Demographics, lipid profiles, blood pressure, BMI, SLEDAI-2K, SDI, disease duration, and treatment data were collected. Physical function and quality of life were assessed using the LupusQoL and PROMIS Physical Function T scores. Univariate and multivariate logistic regression analyses were conducted to identify associations between lipid abnormalities, SLE-related factors, and QoL physical activity measures. Results: A cohort of 169 patients (88.2% female, mean age 39.3 ± 12.4 years) was evaluated to assess the presence of dyslipidemia (23.7%), obesity (BMI ≥ 25, 66.3%), and hypertension (≥130/80 mmHg, 26.0%). Mean SLE duration was 9.2 ± 7.7 years and mean SLEDAI-2K was 11.0 ± 7.0. Among these patients, 52.7% used steroids, 88.2% used antimalarial drugs, and 53.8% used immunosuppressives. Dyslipidemia was associated with lower LupusQoL physical scores (adjusted OR 0.986; 95% CI 0.972–1.000; p = 0.0446). No significant associations were found between lipid levels and the PROMIS Physical Function T score. Conclusions: In this Saudi SLE cohort, dyslipidemia and other modifiable CVD risks were common. Dyslipidemia correlated with poorer LupusQoL-specific physical scores, which highlights the importance of lifestyle changes in patients with SLE. Full article

Background/Objectives: Peripheral-blood transcriptomic profiling can capture molecular heterogeneity in systemic lupus erythematosus (SLE), but discovery-stage signatures often show limited transportability across cohorts and validation layers. This study aimed to establish a staged whole-blood transcriptomic framework and to derive a compact, biologically interpretable activity score. Methods: Public whole-blood bulk transcriptome cohorts were organised into discovery, public validation, and single-cell reference layers. Local orthogonal validation included a peripheral blood mononuclear cell (PBMC) reverse transcription quantitative PCR (RT-qPCR)/flow-cytometric cohort and an expanded whole-blood RT-qPCR validation set. Discovery-stage BloodGen3 profiling included 233 samples, comprising 170 SLE and 63 healthy controls, and endotype discovery was restricted to SLE samples. Candidate genes were compressed into two 6-gene panels, with final selection adjudicated through staged public validation. Results: Two working whole-blood endotypes were identified, characterised by lymphoid versus myeloid/neutrophil-inflammatory polarisation. Although pre6-any showed a marginal discovery-stage advantage, the predefined integrated public-stage adjudication favoured pre6-balanced (MMP9, MYL9, HAL, CTLA4, CD40LG, VPREB3), which was locked as the final panel. In the PBMC cohort, the locked score discriminated SLE from healthy controls (AUC 0.838) and high from low/moderate disease activity (AUC 0.719), with associations with SLEDAI, complement C3/C4, and monocyte subpopulations. In the expanded whole-blood validation set, the score showed SLE-versus-HC discrimination (AUC 0.888, 95% CI 0.821–0.954), high versus low/moderate activity discrimination (AUC 0.918, 95% CI 0.831–0.980), and association with SLEDAI (ρ = 0.819, p = 1.25 × 10⁻¹⁵). Conclusions: This staged framework yielded a compact myeloid–lymphoid activity score supported across public and local validation layers. The score should be interpreted as a research-grade relative activity score and warrants prospective evaluation in SLE. Full article

Thalassemia is an inherited hemoglobin disorder caused by reduced or absent globin chain synthesis, with heterogeneous distribution worldwide and in Brazil. Back-ground/Objectives: This systematic review aimed to estimate the frequency of thalas-semia in the Brazilian population according to thalassemia type, geographic region, and population characteristics, as well as to evaluate the impact of diagnostic methods on frequency estimates. Methods: A systematic review was performed following PRISMA 2020 recommendations, in January 2026, including original studies conducted in Brazil-ian populations that reported thalassemia frequency data. Results: Thirty-six studies met the inclusion criteria, of which 77.8% were classified as high quality. The overall average frequency of thalassemia in Brazil was 7.5%, varying according to thalassemia type and diagnostic approach. The mean frequency of alpha thalassemia carriers was 12.3% (range: 5.5–54.0%), with regional variation from 5.79% in the Midwest to 17.3% in the Southeast. The −α^{3.7 kb} deletion was the most frequently reported mutation na-tionwide. Beta thalassemia showed a mean frequency of 2.81% (range: 0.24–18.1%), with regional values ranging from 0.59% in the Southeast to 12.2% in the North and a wide spectrum of pathogenic variants. Distinct frequency patterns were observed in populations with inherent interpretative bias, including individuals with sickle cell trait, systemic lupus erythematosus, microcytosis, and Black populations. Molecular diagnostic methods demonstrated higher sensitivity, enabling the detection of asymp-tomatic carriers and reducing false-negative results. Conclusions: These findings pro-vide a comprehensive epidemiological overview of thalassemia in Brazil and reinforce the importance of molecular diagnostics for accurate screening, genetic counseling, and the development of public health strategies. Full article