Lupus最新文献

BackgroundSystemic Lupus Erythematosus (SLE) exhibits marked sex-based difference. Understanding these sex-specific variations in clinical manifestations and autoantibody profiles, particularly within diverse ethnic cohorts like Chinese populations, is crucial for advancing personalized management strategies.MethodsWe retrospectively analyzed data from 1029 SLE patients (121 males, 908 females). Comprehensive immunological profiles, including complement C3, C4, CH50, antinuclear antibodies (ANA) titers and patterns, and antiphospholipid (aPL) antibodies, were assessed. Statistical analyses were performed to identify sex-specific prevalence and correlation patterns between autoantibodies and clinical indicators.ResultsDistinct autoantibody patterns emerged by sex. The speckled ANA pattern was more prevalent in males (84.1% vs 53.5%) and anti-Smith (Sm) antibodies were significantly higher in females (34.4% vs 19.8% in males; P = .001). No sex differences were found in ANA titers or aPL antibodies. Females had significantly lower complement levels and higher mean SLEDAI-2K scores (P < .001), while males showed more cardiovascular (P = .039) and pulmonary involvement (P = .026). Sex-specific correlations were evident: males displayed positive autoantibody-autoantibody correlations (e.g., anti-Sm vs anti-RNP), whereas females showed broader correlations, particularly between complement components and disease activity, serum creatinine, and anti-double-stranded DNA (dsDNA) antibodies, reflecting established markers of disease activity and renal involvement. Anti-Sm positivity linked to lower complement in both sexes. Notably, females with anti-Sm had increased anti-dsDNA positivity and elevated SLEDAI-2K, while males with anti-Sm showed higher 24-h urinary protein (P = .02), directly linking anti-Sm to renal involvement in males, a key aspect of male SLE severity.ConclusionsThis study highlights significant sex-based variations in autoantibody patterns and their clinical associations in a Chinese SLE cohort. The distinct prevalence of ANA patterns and anti-Sm antibodies, coupled with sex-specific immunological correlation networks, underscores the complex interplay of immune factors.

BackgroundCotrimoxazole (trimethoprim-sulfamethoxazole) is widely used for infection prophylaxis in immunocompromised patients, including those with lupus nephritis. Although generally well tolerated, rare cardiovascular adverse effects may occur and are not well recognized.Case presentationWe report the case of a 43-year-old man with newly diagnosed class IV lupus nephritis who developed a high-grade atrioventricular block (AVB) shortly after initiation of cotrimoxazole prophylaxis. The patient had no previous cardiac disease, normal renal function, and normal serum potassium levels at presentation. Cotrimoxazole was discontinued immediately, leading to complete recovery of atrioventricular conduction within 7 days. No recurrence occurred during follow-up.DiscussionWhile AVB has been associated with cotrimoxazole in the context of acute kidney injury or hyperkalemia, this case demonstrates a potential direct drug-induced nodal toxicity, as no metabolic or structural abnormalities were identified. The temporal relationship, absence of alternative explanations, and reversibility after drug withdrawal support a probable causal association between cotrimoxazole and AVB.ConclusionThis case highlights the importance of considering cotrimoxazole as a potential, reversible cause of atrioventricular conduction disturbances, even in patients with normal renal and electrolyte profiles. Clinicians should be aware of this possible complication and monitor electrocardiographic changes when prescribing cotrimoxazole, particularly in patients receiving immunosuppressive therapy.

ObjectivesSystemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a highly heterogeneous presentation. Thrombocytopenia (TP) is an uncommon manifestation in SLE patients and is often associated with major organ involvement and poor prognosis. In this study, we aimed to evaluate the prevalence of TP in SLE patients and analyze its association with demographic and clinical factors.MethodsWe utilized data from the ACR's Rheumatology Informatics System for Effectiveness (RISE) registry, a large, electronic health record-enabled database that collects data as part of routine clinical care. The study included patients who were ≥18 years old, had ≥2 SLE diagnostic codes recorded ≥30 days apart between 2016 and 2022, and had a valid complete blood count (CBC) recorded within 1 year of the second SLE code. Thrombocytopenia (TP) was classified based on the lowest platelet count within 1 year of the second SLE code: mild: 100,000-150,000/µL, moderate: 50,000-99,000/µL, and severe: <50,000/µL. We reported the frequency of TP by demographic and clinical characteristics. To identify factors associated with moderate-to-severe TP, we employed multi-level logistic regression models, controlling for covariates and accounting for clustering by practices.ResultsThe study included 30,062 patients (91.2% female; mean age: 56 years, SD: 16). The frequencies of TP and severe TP were 9.3% and 0.5%, respectively. Patients with moderate-to-severe TP had significantly higher frequencies of male sex, African-American and Hispanic ethnicity, lupus nephritis, leukopenia, anemia, hypocomplementemia, anti-dsDNA positivity, end-stage renal disease, thrombosis, hemolytic anemia, antiphospholipid syndrome, and multiple comorbidities compared to other SLE patients. Multivariable logistic regression analysis demonstrated persistent independent associations of sex, race/ethnicity, multiple comorbidities, positive dsDNA, and hypocomplementemia with an increased risk of moderate-to-severe TP in SLE.ConclusionsThe RISE registry revealed that severe TP was less common in SLE patients from community practice compared to previously reported data from selected tertiary centers. Serologically active SLE, multiple comorbidities, male sex, and non-white race were identified as independent factors associated with TP in this database. Further studies are needed to elucidate the exact mechanisms and clinical significance of TP in SLE.

ObjectiveTo analyze the 30-year trajectory of organ damage accrual and damage-free survival (DFS) in a registry-based cohort of Colombian patients with systemic lupus erythematosus (SLE) enrolled in the ARTMEDICA program for autoimmune diseases.MethodWe conducted a retrospective registry-based follow-up study including patients aged ≥18 years, treated between March 2011 and August 2017, who met the 2012 SLICC classification criteria for SLE. Organ damage was assessed using the SLICC/ACR Damage Index (SDI), and disease activity and relapses were evaluated with the SLEDAI-2K. Mean annual change ratios (MACR) in SDI were estimated using multilevel generalized linear models. Parametric survival models for interval-censored data were used to assess overall and system-specific DFS.ResultsA total of 559 patients were included, with a mean follow-up of 14.7 years; 96.6% were female, and the median age at diagnosis was 30 years (IQR: 20-48). The median number of relapses was 3.5 (IQR: 1-8). Mean SDI increased linearly to 1.24 (95% CI: 1.08-1.40) at 15 years and continued to 1.53 (95% CI: 1.16-1.90) at 30 years. Median organ DFS was 7.2 years (95% CI: 5.8-8.5), with substantial variability across systems. Myelopathy (MACR 2.24; 95%CI 1.26-3.98), cellular casts (MACR 2.15; 95%CI 1.09-4.22), seizures (MACR 1.82; 1.30-2.55) and disease activity (MACR 1.22; 95%CI 1.10-1.35) were associated with faster damage accrual.ConclusionThe trajectory of organ damage accrual underscores the long-term burden of SLE and the need for comprehensive interventions, particularly in patients with high-risk clinical features.

ObjectiveThis scoping review aimed to explore studies concerning frailty in patients with SLE, focusing on clarifying the prevalence of frailty, the assessment tools used, the influencing factors, and the adverse effects of frailty on the health outcomes of patients with SLE, and to suggest future research directions.MethodsA systematic search was conducted in PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, WeiPu (VIP), and China Biomedical Literature Service System for studies related to frailty in SLE patients. The search timeframe extended from the inception of the databases to July 26, 2025. Information from the included literature was extracted and summarized.ResultsA total of 22 studies were included. Qualitative age stratification reveals higher frailty prevalence in elderly SLE patients (43.7%-83.5%) versus stable rates in non-elderly adults (16.0%-28.8%); unstratified cohorts show notably wider variation (6.2%-80.9%). Seven evaluation tools were identified, with SLICC-FI and FP being the most frequently used. Influencing factors were categorized as sociodemographic, disease-related, medication-related, and other factors. The adverse effects of frailty on the health outcomes of SLE patients included increased emergency department utilization, hospitalization rate, readmission rate, mortality, and risk of complications. Declines in physical function, activity ability, quality of life, and potential cumulative injuries, pain, fatigue, and disability were also observed.ConclusionA difference in frailty prevalence exists between elderly and elderly-excluded adult SLE patients, indicating the need for age-stratified management strategies. The SPPB is currently not advised for frailty assessment in SLE patients. Regarding the remaining six tools, their diverse characteristics necessitate multifactorial considerations in clinical adoption. Current evidence regarding the influencing factors of frailty in SLE remains insufficient, necessitating focused investigations of modifiable factors. While frailty substantially compromises the health status of patients with SLE, no intervention studies have been identified in the extant literature. Prioritizing intervention research is a critical pathway for delaying frailty progression and enhancing the quality of life in this vulnerable cohort.

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease with a scarcity of effective treatment options and considerable side effects linked to current therapies. Withania somnifera, is rich in phytochemicals that have demonstrated immunomodulatory and anti-inflammatory effects, suggesting its promise as a natural therapeutic candidate for SLE.MethodsAn in silico methodology explored the therapeutic potential of W. somnifera phytocompounds for SLE. Phytochemicals were obtained from Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) and KNApSAcK databases, followed by virtual screening using SwissADME, MOLSOFT, and ProTox 3.0 to identify drug-like and non-toxic candidates. Target genes were predicted using SwissTargetPrediction and STITCH, while SLE-associated genes were compiled from GeneCards and Online Mendelian Inheritance in Man (OMIM). The intersection of these genes was analyzed to construct a protein-protein interaction network, with hub genes identified through Cytoscape. Molecular docking and 100 ns Molecular Dynamic simulations, with Molecular Mechanics, General Born Surface Area (MM-GBSA) free energy calculations, were conducted for lead compounds against top hub proteins.ResultsThe study identified three phytocompounds-vanillic acid, (+)-catechin, and withanolide K-that show favorable pharmacokinetic and toxicity characteristics. Network analysis identified 161 common target genes, with Caspase 3 (CASP3), HIF1A (Hypoxia-inducible factor 1-alpha subunit), Interleukin 1 beta (IL1B), and Interleukin 6 (IL6) as significant hub proteins. Docking studies revealed (+)-catechin and withanolide K have strong binding affinities with IL6 and CASP3. Molecular dynamics simulations confirmed complex stability, and MM-GBSA calculations showed favorable binding free energies, especially in (+)-catechin-protein interactions.Conclusions(+)-Catechin and withanolide K are promising biomolecules for SLE, demonstrating a strong binding affinity with key proteins linked to the disease. These results offer a computational basis for experimental validation and the potential development of safer, plant-based therapies for SLE.

BackgroundWomen with systemic lupus erythematosus (SLE) are at an increased risk of infection from the human papillomavirus (HPV) and subsequently HPV-mediated malignancies and genital warts. The HPV vaccine is a highly effective intervention in preventing HPV infection and is recommended in SLE patients. We determined HPV vaccination rates and factors associated with decreased vaccination uptake in women living with SLE.MethodsWe conducted a cross-sectional study in which we enrolled women with SLE (aged 21-45) for whom the HPV vaccine is recommended for by the US Food and Drug Administration (FDA). The primary outcome was self-reported HPV vaccination as recommended by the Advisory Committee on Immunization Practices (ACIP). We collected demographics, clinical characteristics, knowledge on HPV and vaccines, and items for constructs of the Health Belief Model (HBM) and determined associations between these covariates and HPV vaccination status.ResultsWe enrolled 75 women with SLE. Median age was 33 (IQR 27-40) and 20 (27%) had received HPV vaccination. Older women and Spanish-speaking patients were less likely to have received the HPV vaccine. When examining HBM constructs an increase in 'perceived barriers' (e.g. not knowing where to get the vaccine) was associated with no vaccination (r = -0.41, p < 0.01). Increased report of 'cues to action' (e.g. My doctors told me lupus increases risk for cervical cancer) was associated with increased HPV vaccination (r = 0.30, p < 0.01). After multivariable adjustment of significant covariates, age remained at significantly decreased odds for HPV vaccination (OR 0.82, 95% CI 0.73-0.93).ConclusionWe found low HPV vaccine uptake among racial and ethnically diverse women with SLE. Older age, Spanish language, increased perceived barriers, and increased cues to action were significantly correlated with HPV vaccination. This data highlights potential strategies for providers to use to improve HPV vaccination in this patient population.

BackgroundMonogenic lupus is a rare form caused by single pathogenic gene variants, leading to diverse clinical symptoms from multi-organ involvement. Variants in Protein Kinase Cδ (PRKCD) are known contributors, though remain underreported.ObjectiveTo describe the phenotypic, genetic, and outcome profiles of Arab children with monogenic lupus and PRKCD deficiency.MethodsWe retrospectively reviewed medical records of children with PRKCD deficiency lupus at two institutions in Saudi Arabia and Oman. The cohort included genetically confirmed and clinically suspected cases (due to unavailable testing in deceased siblings). Demographic, clinical, genetic, and follow-up outcome data were collected and analyzed.ResultsSeven children (four females) from three unrelated consanguineous Arab families were identified, with four having confirmed PRKCD variants. All presented before the age of 2 years with fever and multi-organ involvement. Recurrent infections were common, with three patients developing BCGitis. All had high ANA, ds-DNA, and APL, with variable positivity for other autoantibodies. Complement studies revealed low C₃/C₄, and reduced C1q and CH₅₀ in four patients. Treatment included corticosteroids and sequential immunosuppressive therapy, with five patients receiving biologic agents. While four achieved low disease activity on intensive treatment, three died due to severe disease and serious infections.ConclusionOur findings demonstrate that PRKCD deficiency is associated with autosomal recessive monogenic lupus, characterized by severe and potentially fatal outcomes. They also confirm the link with BCGitis susceptibility. The observed heterogeneity in disease course and treatment response highlights the need for precision medicine and warrants further investigation.

ObjectivesTuberculosis (TB) may increase morbidity and mortality of systemic lupus erythematosus (SLE) patients. The aim of the study was to determine the risk factors associated with TB in SLE patients.MethodsThis case-control study included SLE patients from the Hasan Sadikin Lupus Registry (HSLR) cohort between 2008 and 2024. Lupus patients with TB (cases) were matched by age with those without TB (controls). TB risk was estimated as adjusted OR (aOR) with 95% CI using univariate and multivariable logistic regression analyses.ResultsIn total, 90 SLE patients with TB and 270 without TB were included, predominantly female (n = 342; 95%). The median SLE duration to TB diagnosis was 30 (range 8-95) months, of which 56.7% (n = 51) had pulmonary TB, and 21.1% (n = 19) had extrapulmonary TB with meningitis and lymphadenitis being the most prevalent. Logistic regression analysis showed that SLE duration <9 months (aOR 4.04; 95% CI 1.78-9.18), history of TB contact (aOR 3.67; 95% CI 1.31-10.30), history of methylprednisolone ≥24 mg/day for ≥4 weeks (aOR 1.96; 95% CI 1.06-3.63), using <2 disease-modifying antirheumatic drugs (DMARDs) (aOR 3.34; 95% CI 1.89-5.90), and lymphopenia (aOR 2.84; CI 95% 1.65-4.91) were associated with TB (P < .05).ConclusionsAmong SLE patients living in TB endemic country, TB contact, high dose corticosteroid, and lymphopenia increase risk of TB. Of note, lower disease duration and using <2 DMARDs are also associated with TB. Further research is necessary to evaluate the need of TB prophylaxis in SLE patients with these risk factors.

ObjectivesThe main challenge in the care of patients with primary antiphospholipid syndrome (APS) or associated to systemic lupus erythematosus (SLE) is to determine whether patients will experience new events that may impair their clinical outcome. Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of the Toll like receptor (TLR4) pathway, which is involved in APS. Plasma soluble TREM-1 (sTREM-1) levels indicate increased receptor activation and were significantly greater in thrombotic primary APS patients compared to controls. This prospective cohort study investigated the predictive value of plasma sTREM-1 levels at inclusion for the occurrence of thrombotic events or death in patients with APS, antiphospholipid antibodies (aPLs) and/or SLE.MethodsSerum sTREM-1 levels were measured at inclusion in 108 patients with APS, isolated aPL or SLE followed during 46 months. The primary outcomes included thrombosis, death and obstetrical morbidity. The occurrence of the first event of interest and predictors were modeled in a multivariable Cox model.ResultsDuring follow-up, 15 of the 108 patients presented with thromboses (14%), 5 patients died (5%), and 3 women experienced obstetrical morbidities (3%). Elevated serum sTREM-1 levels were an independent predictor for the occurrence of the composite outcome (HR 7.54 [95% CI; 2.44-23.31] p < .001). In addition, sTREM-1 levels were greater in patients with APS than patients with isolated aPL (p < .01).ConclusionHigh levels of sTREM-1 at inclusion predicted the occurrence of a thrombotic and obstetric event or death in patients with aPL and/or SLE. Therefore, sTREM-1 represents a potential new prognostic biomarker in these patients.