OBJECTIVE:To develop and temporally validate a clinical prediction model for identifying bacterial infection (BI) among hospitalised patients with SLE. METHODS:We retrospectively included hospitalised patients with SLE admitted for BI or active disease between January 2023 and January 2026. Admissions from January 2023 to January 2025 formed the training cohort, and admissions from February 2025 to January 2026 formed the temporal validation cohort. BI included infection with or without concomitant active SLE; non-infected active (NA) SLE was the comparator. Candidate predictors were prespecified according to clinical relevance, prior literature, routine availability and missingness. LASSO (Least Absolute Shrinkage and Selection Operator) regression was applied across imputed datasets, and final coefficients were estimated using multivariable logistic regression and pooled using Rubin's rules. Performance was assessed by discrimination, calibration, full-workflow bootstrap internal validation, same-centre temporal validation and decision curve analysis. RESULTS:The training cohort included 395 admissions (170 BI, 225 NA), and the validation cohort included 200 admissions (75 BI, 125 NA). The final model included age, disease duration, previous hospitalisation for BI, fever, white cell count, C reactive protein (CRP), procalcitonin, C4 hypocomplementemia and ordinal SLE-DAS (Systemic Lupus Erythematosus Disease Activity Score) category. Training area under the curve (AUC) was 0.869 (95% CI 0.833 to 0.905), exceeding CRP (0.771), procalcitonin (0.682) and the erythrocyte sedimentation rate/C reactive protein (ESR/CRP) ratio (0.736). Full-workflow bootstrap validation yielded an optimism-corrected AUC of 0.837 and corrected Brier score of 0.162. Same-centre temporal validation showed stable discrimination (AUC 0.852, 95% CI 0.794 to 0.910), acceptable calibration and preserved net benefit. CONCLUSIONS:A routinely available, interpretable model identified BI among hospitalised patients with SLE using NA SLE as the comparator. C4 hypocomplementemia and higher SLE-DAS categories should be interpreted as markers of disease activity predominance rather than protective factors against infection. Multicentre external validation and clinical impact studies are required.
OBJECTIVE:This study aimed to compare 25-hydroxyvitamin D (25-(OH)D) levels and peripheral lymphocyte subsets between children with new childhood-onset SLE and healthy controls across different seasons, and to explore the relationships of seasonal 25-(OH)D concentrations with the disease activity and peripheral lymphocyte subsets in paediatric patients with SLE. METHODS:A retrospective study was conducted, enrolling 285 patients with new childhood-onset SLE and 175 healthy children. All participants were divided into a winter-spring group and a summer-autumn group according to sampling seasons. Serum 25-(OH)D levels and peripheral lymphocyte subsets were detected and quantified. RESULTS:Compared with healthy controls, patients with SLE presented with significantly higher proportions of CD8+ T cells (p<0.05), alongside lower total lymphocyte counts, lower percentages of CD4+ T cells and Natural Killer(NK) cells, reduced CD4+/CD8+ ratio and decreased serum 25(OH)-D levels (all p<0.05). Within the SLE cohort, patients in the summer-autumn SLE group had markedly higher serum level of 25-(OH)D levels than those in the winter-spring group (18.1 vs 22.8 ng/mL; p<0.001). 25-(OH) D deficiency was correlated with a higher prevalence of lupus nephritis, higher Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores and lower serum calcium levels. In both seasonal subgroups, serum calcium and serum albumin showed weak positive correlations with serum 25-(OH)D levels. A moderate negative correlation was observed between SLEDAI-2K scores and 25-(OH)D levels in the winter-spring group, while only a weak negative correlation was detected in the summer-autumn group. CONCLUSIONS:Serum 25-(OH)D levels are affected by seasonal changes and closely correlated with disease activity in children with SLE. Patients with new childhood-onset SLE manifest abnormal peripheral lymphocyte subsets and insufficient 25-(OH)D.
OBJECTIVE:Lupus nephritis (LN) is a potentially severe manifestation of SLE, often resulting in permanent kidney damage. We investigated whether polygenic and/or epigenetic risk is associated with time to LN relapse and whether this association differs by initial therapy. METHODS:Caucasian patients with biopsy-verified LN between 1974 and 2022 (n=149) were genotyped using the Illumina Global Screening Array, and DNA methylation was assessed with the Illumina HumanMethylation450k BeadChip. A weighted Polygenic Risk Score (PRS) based on 55 non-Human leukocyte antigen (HLA) SLE risk gene variants and a Methylation Risk Score (MRS) based on the 17 most differentially methylated cytosine-phosphate-guanine sites identified in SLE-control comparison were calculated. Time to LN relapse was analysed using Cox proportional hazards models, adjusted for centre, sex and year of the first LN. RESULTS:Neither PRS nor MRS was associated with time to LN relapse in the overall cohort, irrespective of treatment (PRS: HR=1.00 (0.77-1.30); p=0.99; MRS: HR=1.01 (1.00-1.02); p=0.21). No associations were observed among cyclophosphamide (CYC)-treated patients (PRS: HR=0.81 (0.55-1.20); p=0.29; MRS: HR=1.00 (0.99-1.02); p=0.89). In non-CYC-treated patients, PRS showed a non-significant trend towards shorter time to LN relapse (HR=1.26 (0.88-1.81); p=0.21), with a similar trend for MRS (HR=1.02 (1.00-1.03); p=0.066). Adding MRS to the PRS model improved performance in this subgroup (likelihood ratio test, p=0.028), with significant associations for MRS (PRS: HR=1.56 (0.97-2.50); p=0.066; MRS: HR=1.02 (1.00-1.04); p=0.037). CONCLUSIONS:Genetic and epigenetic susceptibility appears to influence LN relapse risk in a treatment-dependent manner. The absence of an association among patients receiving CYC suggests that initial treatment with CYC may attenuate the impact of genetic and epigenetic predisposition on relapse. These findings support the potential of genetic and epigenetic profiling at LN diagnosis to improve relapse risk stratification and individualise selection of treatment.
OBJECTIVE:To investigate whether MLKL crotonylation is associated with tubular autophagy-lysosome pathway homeostasis in lupus nephritis (LN) and to explore its relationship with RAB1A-mechanistic target of rapamycin (mTOR) signalling. METHODS:Crotonylome proteomics was performed in peripheral blood mononuclear cells from patients with LN, patients with systemic lupus erythematosus without nephritis and healthy controls. Renal biopsy tissues were evaluated for tubulointerstitial fibrosis and autophagy-lysosome pathway-related markers. Mechanistic studies were conducted in lipopolysaccharide-stimulated HK-2 cells. Autophagic flux was assessed using bafilomycin A1. The dependency of mTOR/autophagy changes on RAB1A was tested by siRNA-mediated knockdown. RESULTS:MLKL was identified as a differentially crotonylated protein in LN, with increased crotonylation at K95 and K219. Kidney tissues from patients with LN showed increased fibronectin and collagen III deposition compared with controls, whereas no significant difference was observed between class IV and class V LN. LC3 signal did not differ significantly between groups, whereas LAMP1 expression and LC3-LAMP1 co-localisation were reduced in LN. In HK-2 cells, crotonylation-deficient MLKL mutants were associated with increased LC3-II and reduced p62, whereas K219Q showed the opposite pattern. Autophagic flux assays using bafilomycin A1 showed that K219R-expressing cells had higher LC3-II levels than WT cells both before and after lysosomal inhibition, with comparable BafA1-induced LC3-II accumulation, consistent with increased autophagosome formation rather than impaired lysosomal degradation. HDAC1 knockdown increased MLKL crotonylation and was accompanied by mTOR activation. MLKL crotonylation enhanced RAB1A guanriphosphat osphate (GTP) binding without altering total RAB1A abundance. RAB1A knockdown in MLKL WT-expressing cells attenuated mTOR phosphorylation and partly reversed the autophagy-suppressive marker profile. Sodium crotonate induced an autophagy-suppressive marker profile that was partly reversed by rapamycin. CONCLUSION:MLKL crotonylation is associated with activation of the RAB1A-mTOR axis and altered tubular autophagy-lysosome pathway homeostasis in LN. These findings suggest that tubular injury-related changes in LN may not be fully reflected by glomerulus-based classification alone.
Objective (1) To explore practice patterns and variability in the management of systemic lupus erythematosus (SLE) in Spain, including the adoption of the treat-to-target (T2T) strategy; (2) to identify key multilevel contextual factors, barriers and facilitators; and (3) to propose strategies to overcome the identified barriers.Methods A qualitative analysis was conducted using a contextual analysis (CA) framework based on the components of the Basel Approach for coNtextual ANAlysis. This involved collecting contextual data through a literature review and other relevant sources, as well as collecting primary data to address gaps via structured focus groups with rheumatologists.Results Considerable variability in SLE management was described by rheumatologists across regions and healthcare centres. Major barriers included disease complexity, delayed diagnosis, workforce shortages, limited training and awareness among healthcare professionals, insufficient multidisciplinary collaboration, underutilisation and lack of standardisation of clinical indices, inadequate patient education and poor integration of patient-reported outcomes into electronic medical records. Implementing T2T and clinical guidelines was rare due to perceived complexity, time constraints, a lack of digital support and limited training. Rheumatologists proposed several strategies, including improved training, structured referral pathways, digital solutions, shared decision-making tools, practical checklists and the development of multidisciplinary care networks.Conclusions This CA highlights significant challenges in implementing evidence-based SLE management in Spain, particularly regarding the adoption of the T2T strategy. Addressing contextual factors at the healthcare provider, organisational and patient levels is crucial for improving the quality of care and patient outcomes. These findings lay the groundwork for designing tailored national-level implementation initiatives.
Objective Our objective is to estimate the prevalence and incidence of interstitial lung diseases (ILDs) among adults with systemic lupus erythematosus (SLE) and to explore possible differences in reported prevalence and incidence of SLE-ILDs between clinical observational and register-based studies.Method EMBASE, MEDLINE, Cochrane Library and Scopus were searched for eligible studies investigating SLE-ILDs prevalence and/or incidence. Risk of bias was assessed using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. Data were extracted in a predefined Excel spreadsheet by two reviewers independent and blinded to each other. Pooled weighted prevalences and incidences were calculated with corresponding 95% CIs, visualised in forest plots. Heterogeneity was assessed with I2 test.Results Ninety-eight studies comprising 155 964 participants were included in the systematic review and meta-analyses. The pooled weighted SLE-ILDs prevalence was 11.0% (9.0% to 13.0%), with substantial heterogeneity (I²=99.9%), and 18% when identifying SLE-ILDs with chest high-resolution CT (HRCT) scans. Clinical observational studies reported a higher prevalence of 25.0% (19.0% to 31.0%) compared with register-based studies 7.0% (5.0% to 8.0%). The incidence analysis was based on three registry-based studies and estimated an incidence of 4.9 per 1000 person-years (−0.5 to 10.3) with substantial heterogeneity (I² = 99.8%).Conclusion ILDs appear to be a prevalent manifestation in SLE with a pooled prevalence estimate of 11.0%, although this estimate should be interpreted with caution due to substantial heterogeneity across studies. HRCT-based studies reported a higher prevalence (18.0%), suggesting that diagnostic modality influences prevalence estimates. The incidence estimate (4.9 per 1000 person-years) should be interpreted as exploratory because it was based on only three registry-based studies. Overall, the findings suggest that ILD may be more common in SLE than previously assumed, highlighting the importance of awareness of pulmonary manifestations. We found the prevalence to be higher in clinical observational studies than register-based studies.PROSPERO registration number CRD420250642237.
Objective Epidemiologic data on falls in the population with systemic lupus erythematosus (SLE) remain sparse. We estimated the prevalence and correlates of falls among adults with SLE and compared SLE prevalence estimates with those in the general US population. Methods We assessed falls in a nested cross-sectional study within two pooled population-based SLE cohorts in California (3/2025–2/2026) and Georgia (10/2019–5/2022). Stratified prevalence was assessed with marginal estimates from logistic regression models with falls as the outcome. Age-standardised and sex-standardised estimates in SLE were compared with 2023 US population estimates (ages ≥45 only). Results In this pooled SLE cohort (N=780; mean age, 47.9; 91.9% women; 14.5% Asian, 51.7% black, 13.2% Hispanic), 26.0% reported any fall in the prior year; among these, 59.1% reported falling two times or more and 31.0% reported associated injuries. General factors (oldest vs youngest age (37.4% vs 20.7% for ≥65 vs 20–44)) and SLE-related factors (higher SLE activity (38.5% vs 13.5%), moderate-to-severe depressive symptoms (40.0% vs 23.7%), greater pain interference (43.8% vs 16.5%), greater fatigue (39.2% vs 18.8%) and lower cognitive function (39.7% vs 18.9%)) were statistically significantly associated with higher fall prevalence in the SLE cohort. Among those aged ≥45, the age-standardised and sex-standardised prevalence estimate in the SLE population (22.9%) was similar to the US population estimate (19.5%). Conclusion The prevalence of falls in SLE is high and recurrence is common, suggesting clinical assessment of falls—especially in those with high disease activity and symptoms—is important in SLE.
Objectives Investigate the role of antiphospholipid antibodies (aPL) in determining subclinical microvascular alterations in patients with primary antiphospholipid syndrome (PAPS) and antiphospholipid carriers, using posterior segment optical coherence tomography angiography (OCTA) and spectral-domain OCT (SD-OCT).Methods In this monocentric, cross-sectional study, PAPS and aPL-carrier patients and age-matched and sex-matched healthy controls were enrolled. OCTA and OCT were performed to assess vessel density (VD) in the superficial and deep retinal capillary plexi and to obtain high-resolution sectional retinal images.Results 38 patients from the aPL-cohort (30 PAPS and 8 aPL-carriers) and 32 matched healthy controls were enrolled. OCTA revealed reduced superficial and deep whole en face VD, particularly at the parafoveal level. SD-OCT demonstrated thinning of the central and outer regions of peripapillary retinal nerve fibre layer and of the macular, inner and outer plexiform, nuclear and nerve fibre layers. Increased thickness was observed in the inner inferior and superior regions across all retinal layers. No significant associations were found between OCTA parameters and disease duration, thrombotic risk profile, lupus anticoagulant positivity, cumulative drug exposure or treatments with low-dose aspirin or vitamin K antagonists. However, the VD in the superficial whole en face and parafoveal regions remained significantly reduced in the aPL-cohort after adjustment for age and cardiovascular risk factors.Conclusion Subclinical microvascular and structural damage occurs in aPL positive patients without ocular symptoms. This study suggests a possible independent effect of aPL, making the eye a unique, non-invasive window into aPL-related pathogenic mechanisms for early detection and longitudinal monitoring.
OBJECTIVE:Prior studies suggested that maternal systemic autoimmune rheumatic diseases (SARDs) may increase the risk of mental disorders (MDs) in offspring. However, evidence is limited by heterogeneous definitions of autoimmune rheumatic diseases, focusing on specific MDs and scarce data from Asian populations. We aimed to investigate the association between maternal SARDs and the risk of childhood MDs. METHODS:Our study included 1 949 968 maternal-child dyads identified in the Taiwan Maternal and Child Health Database between 2004 and 2015. Maternal SARD diagnoses were identified based on approved catastrophic illness certificates, while childhood MDs were identified by documentation of a relevant diagnostic code in the nationwide health insurance claims data. Cox proportional hazard models were used to examine the association between maternal SARDs and childhood MDs. RESULTS:After a mean follow-up of 11.7 years, there were 774 (19.8%) and 306 907 (15.8%) live births born to mothers with and without SARDs respectively, which developed childhood MDs. Maternal SARDs were associated with an increased risk of childhood MDs (HR, 1.30; 95% CI 1.19 to 1.41). Elevated risks of childhood MDs were observed among offspring of mothers with systemic lupus erythematosus (HR=1.26, 95% CI 1.13 to 1.41), primary Sjogren's syndrome (HR=1.59, 95% CI 1.29 to 1.97), idiopathic inflammatory myositis (HR=1.73, 95% CI 1.06 to 2.83) and systemic sclerosis (HR=1.94, 95% CI 1.15 to 3.28), compared with mothers without SARDs. CONCLUSION:In this nationwide, population-based study from an Asian population, maternal SARDs were associated with higher risks of childhood MDs. Our findings suggest early monitoring of MDs among offspring of mothers with SARDs as part of clinical practice.
OBJECTIVE:A data-driven and expert/patient consensus-based project to develop a revised Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) is under way supported by SLICC, ACR, and the Lupus Foundation of America. Our objective is to report the item generation and reduction phase results for a revised SDI. METHODS:Item generation included a literature review by literature review groups and a Delphi exercise of international systemic lupus erythematosus experts and patients. Item reduction involved Delphi rounds in which items with a median appropriateness score of ≤4 of 9 were excluded. A 14-member item reduction committee assessed remaining items and removed those that did not reflect the damage construct, were rare, or were not feasible to assess. The clinical domain groups then refined the remaining items and their definitions. RESULTS:The Delphi panel included 146 individuals from 35 countries. The Delphi exercise nominated 2,256 items, and the literature review identified 117 items. After removing redundancies, 226 candidate items remained. Subsequent Delphi rounds, followed by review by the item reduction committee and clinical domain groups, resulted in 39 items across 13 domains. Eleven items from the original SDI, including proteinuria and cranial neuropathy, were removed and several new items were proposed, including growth failure/reduced final height and adrenal insufficiency. Severity-based subitems are proposed for 17 items (43.6%). CONCLUSION:This data-driven and expert/patient consensus-based process has proposed 39 candidate items, some with subitems, and definitions for a revised SDI. Weighting of items and subitems is underway to develop a clinical scoring system.
OBJECTIVES:To describe the aetiologies of thrombocytopenia in patients with antiphospholipid syndrome (APS) and to assess the frequency and characteristics of immune thrombocytopenia (ITP), including its association with SLE. METHODS:We retrospectively analysed patients with APS who experienced at least one episode of thrombocytopenia (platelet count <100 x 10ˆ9/L) in a tertiary referral cohort enriched in severe cases, particularly catastrophic antiphospholipid syndrome (CAPS). Individual medical records were systematically reviewed to determine the cause of thrombocytopenia. ITP was stringently defined by exclusion of alternative diagnoses and by a documented response to ITP-specific therapies. Clinical, biological and therapeutic characteristics were analysed. The risk of severe haemorrhagic events was evaluated. RESULTS:Among 351 patients with APS, 102 (29.1%) experienced thrombocytopenia and were included in the study. The median platelet nadir was 34.5 x 10ˆ9/L, and 33 (32.4%) had severe thrombocytopenia (<20 x 10ˆ9/L). The most frequent cause of thrombocytopenia was CAPS (n=75, 73.5%), followed by ITP (n=12, 11.8%), including two patients who had both CAPS and ITP. 11 (10.8%) patients had other identified causes, while thrombocytopenia remained unexplained in six patients (5.9%).Patients with ITP more frequently had associated SLE than those with CAPS (80.0% vs 35.6%, p=0.013). Overall, isolated ITP without SLE accounted for only 0.6% of the entire APS cohort. In survival analysis, a graded increase in the risk of severe haemorrhagic events was observed with increasing thrombocytopenia severity, although the association did not reach statistical significance (HR 2.55, 95% CI 0.94 to 6.94 for platelet nadir <20 x 10ˆ9/L vs >100 x 10ˆ9/L). CONCLUSION:In patients with APS, the underlying cause of thrombocytopenia can be identified in most cases through careful review of medical records. True ITP is uncommon and appears to be exceptionally rare in patients with APS without concomitant SLE. These findings highlight the importance of thoroughly investigating alternative causes of thrombocytopenia and of systematically screening for SLE before diagnosing ITP in patients with APS. TRIAL REGISTRATION NUMBER:NCT02782039.
OBJECTIVE:This study aimed to evaluate the associations of free mycophenolic acid (f-MPA) concentration and total MPA (t-MPA) concentration with treatment response and haematologic toxicity and to determine whether f-MPA provides additional safety-related value for therapeutic drug monitoring (TDM) in patients with paediatric lupus nephritis (LN) treated with mycophenolate mofetil (MMF). METHODS:Sixty-five patients with paediatric LN receiving MMF were prospectively enrolled. The t-MPA and f-MPA were measured simultaneously using validated ultrafiltration and LC-MS/MS. Full pharmacokinetic profiles were obtained over 12 hours, and area under the concentration-time curve (AUC) was calculated for t-MPA (t-MPA-AUC) and f-MPA (f-MPA-AUC). Univariate analysis identified factors influencing efficacy (relapse-free survival) and adverse drug reaction (ADR) over 12 months. Receiver operating characteristic (ROC) curves established predictive thresholds and Kaplan-Meier methods analysed time-to-event. RESULTS:The 12-month relapse-free rate was 78.7% (95% CI 66.6% to 90.9%). Both t-MPA-AUC and f-MPA-AUC significantly correlated with relapse-free survival (ROC AUC 0.70 each; optimal thresholds: t-MPA-AUC=31.63 µg·h/mL, f-MPA-AUC=354.45 ng·h/mL). The average remission duration above these thresholds was 10.88 and 11.00 months. The overall MMF-related ADR incidence was 25.2%, including 17 haematological events (26.2%). The t-MPA-AUC, f-MPA-AUC, glucose, β2-microglobulin and C3 were haematological ADR risk factors. The f-MPA-AUC independently predicted haematological ADRs (optimal threshold: 492.96 ng·h/mL; specificity 86.2%). CONCLUSION:Both t-MPA-AUC and f-MPA-AUC effectively predict MMF efficacy in paediatric LN. However, f-MPA-AUC demonstrates superior predictive value for safety outcomes, specifically haematological ADRs. This supports f-MPA as a potentially better TDM metric for optimising MMF therapy safety in this population.
Objectives CD163 is a macrophage-associated scavenger receptor shed during inflammatory activation, resulting in measurable soluble CD163 in serum (s) and urine (u). Elevated levels have been reported in inflammatory and immune-mediated conditions, including lupus nephritis (LN). This study aimed to investigate the relationship between soluble CD163 levels and intrarenal CD163 expression, evaluating their association with disease activity and treatment response in LN. Methods Forty-five patients with systemic lupus erythematosus (SLE) were included (20 active LN, 10 inactive LN, 15 active extra-renal SLE), together with 20 matched healthy controls. Serum and urine samples were collected at baseline alongside renal biopsy in active LN; 6-month follow-up samples were available for 12 active LN patients. CD163 was measured by ELISA; urinary CD163 was normalised to spot urine creatinine. Renal biopsies from 20 active LN patients were evaluated for CD163+ macrophage density. Results uCD163 was higher in active LN (a renal Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) flare (UPCR ≥0.5 g/g) with biopsy-proven active lesions) than in inactive LN and active extra-renal SLE (both p<0.001), discriminating active from inactive LN (area under the curve (AUC) 0.97) and from extra-renal SLE (AUC 0.89). uCD163 correlated with the National Institutes of Health activity and chronicity indices activity index (ρ=0.55, p=0.016) and with glomerular CD163+ macrophage density (the number of CD163+ macrophages per glomerulus quantified by immunohistochemistry; ρ=0.65, p=0.006), but not with chronicity. Glomerular CD163+ macrophage density also correlated with sCD163 (ρ=0.60, p=0.01) and uCD163 (ρ=0.63, p=0.009). After 6-month induction, uCD163 fell from 7.41 to 1.55 ng/mg (p<0.001). Conclusion uCD163 distinguishes active LN from inactive renal and extra-renal disease and tracks treatment response. The association with intrarenal CD163+ macrophages supports its biological relevance as a non-invasive marker of renal inflammation, complementary to histopathology when repeat biopsy is not feasible. These findings support uCD163 as a candidate non-invasive tool for identifying active LN and monitoring treatment response in SLE, warranting validation in larger prospective cohorts.
Objectives To estimate the risk of venous thromboembolism (VTE) in a nationwide cohort of newly diagnosed patients with SLE and in a cohort of established patients with SLE at Karolinska University Hospital compared with the general population.Methods Individuals with SLE were identified from the National Patient Register and matched to general population comparators on age, sex and residence. Follow-up was from diagnosis/matching until incident VTE, death, emigration or study end. The Karolinska cohort was followed from enrolment and additionally stratified by lupus nephritis (LN) and antiphospholipid antibody (aPL) positivity. Incidence rates (IR) of VTE were estimated and adjusted HRs with 95% CIs were estimated using Cox models. Time-dependent adjusted HRs were estimated using flexible parametric survival models.Results In the nationwide cohort (N=4335), the mean age at inclusion was 49 years, 83% were female and mean follow-up was 7.4 years. The VTE IR was 8.8 per 1000 person-years compared with 2.8 in comparators, corresponding to an HR of 3.3 (95% CI 2.9 to 3.8). In the Karolinska cohort (N=784), the HR was 4.9 (95% CI 3.7 to 6.5). VTE risk was highest in the first few years after SLE diagnosis. LN was not significantly associated with VTE, and aPL positivity was associated with a 60% higher hazard, which was non-significant and attenuated after excluding individuals with prior VTE.Conclusion SLE is associated with an over threefold increased risk of VTE, in particular soon after SLE diagnosis, underscoring the need for individualised VTE risk assessment.
Background Diagnostic attribution of neuropsychiatric symptoms in SLE (NPSLE) remains challenging. This study evaluated whether cerebrospinal fluid (CSF) antisuprabasin (SBSN) antibody can serve as a diagnostic biomarker for NPSLE.Methods In this single-centre, prospective cohort study, patients with SLE presenting with new-onset neuropsychiatric or neurological symptoms were screened between January 2022 and October 2025. Final diagnoses were adjudicated by an independent committee blinded to CSF anti-SBSN antibody results. Patients were classified as NPSLE, SLE with central nervous system infection (SLE-CNSI) or SLE without NPSLE or CNS infection (SLE-Other). CSF anti-SBSN antibody levels were measured by ELISA. Diagnostic performance was assessed for identifying NPSLE against a combined non-NPSLE comparator group comprising SLE-CNSI and SLE-Other.Results Among 190 screened patients, 148 were included in the final analysis, including 48 with NPSLE, 59 with SLE-CNSI and 41 with SLE-Other. CSF anti-SBSN antibody levels showed a stepwise increase across groups, with median concentrations of 47.60 ng/mL in SLE-Other, 72.82 ng/mL in SLE-CNSI and 88.94 ng/mL in NPSLE; all pairwise comparisons were significant (all p<0.001). For identifying NPSLE versus non-NPSLE comparators, CSF anti-SBSN antibody achieved an area under the receiver operating characteristic curve (AUROC) of 0.830, with a sensitivity of 0.812 and specificity of 0.740 at the optimal cut-off of 76.36 ng/mL. CSF anti-SBSN antibody had a higher AUROC than CSF white blood cell count (0.830 vs 0.743; p=0.041) and serum antiribosomal P antibody (0.830 vs 0.665; p=0.003). The three-marker model further increased the AUROC to 0.892 and significantly outperformed CSF anti-SBSN antibody alone (p=0.009).Conclusion CSF anti-SBSN antibody was significantly elevated in NPSLE and demonstrated good diagnostic performance for identifying NPSLE among patients with SLE presenting with neuropsychiatric symptoms. These findings support CSF anti-SBSN as a promising candidate diagnostic biomarker for NPSLE, particularly when combined with conventional CSF inflammatory and serological markers.
Objective Childhood-onset SLE (cSLE) is often described as more severe than adult-onset disease (aSLE) based largely on cross-sectional studies. We examined differences in disease characteristics, medication use and long-term outcomes between cSLE and patients with aSLE in adulthood using longitudinal data from a national cohort to address this knowledge gap. Methods A retrospective cohort study was conducted using the Australian Lupus Registry and Biobank. Data included demographics, disease duration, autoantibody profile, classification criteria, time-adjusted mean SLE Disease Activity Index 2000 (SLEDAI-2K AMS), SLE Damage Index (SDI) and SF36 health-related quality of life data. Key outcomes were AMS and time in the Lupus Low Disease Activity State (LLDAS) and damage accrual. Bivariate tests were used for group comparisons. Results Of 519 patients with SLE enrolled between 2011 and 2022 with ≥12 months of data available, 68 (13%) had cSLE. Median (IQR) age at enrolment was 39 (30–51) years; 88.1% female; majority were of white or Asian ethnicity. At baseline, more patients with cSLE had damage (SDI≥1) (53% vs 40%, p=0·05) and renal involvement (62% vs 37%, p<0·001). Over median (IQR) follow-up of 5 (2·6–9·3) years, patients with cSLE had higher disease activity (median (IQR) AMS 5·0 (3·0–6·4) cSLE vs 3·6 (1·9–5·1) aSLE, p<0.001), were more likely to be in High Disease Activity Status (SLEDAI-2K ≥10 ever) and were less likely to achieve LLDAS-50 (36% vs 51%, p=0·036). Flare rates, damage accrual and quality of life during follow-up were similar between groups. Conclusions Adults with cSLE entered adult follow-up with higher baseline damage and continued to experience a higher longitudinal disease activity burden than patients with aSLE. These findings highlight the importance of early recognition, consistent longitudinal monitoring and timely escalation of therapy during earlier years of disease to reduce long-term disease burden.
Objective Belimumab has been proven to be effective for treating refractory lupus nephritis. However, the meaningful renal response is still far from satisfactory. This study sought to identify immunological biomarkers to stratify patients who are likely to benefit from belimumab therapy.Methods We retrospectively reviewed the medical records of patients with refractory lupus nephritis who received 6 months belimumab treatment. Complete response (CR), partial response (PR) and no response (NR) were evaluated, and the predictors of CR were identified.Results A total of 28 patients with refractory LN were enrolled. The proportions of CR, PR and NR at 6 months were 39.29%, 32.14% and 28.57%, respectively. The baseline CD19+B cell proportions were significantly higher in CR patients than those in non-CR patients (19.30% vs 10.72%, p<0.001). In the binary logistic regression, baseline CD19+B cell proportion was identified as a predictor of CR in both univariate analysis (OR 1.359, 95% CI 1.098 to 1.683, p=0.005) and exploratory multivariate analysis adjusting for 24-hour urinary protein (OR 1.349, 95% CI 1.092 to 1.665, p=0.005). Receiver operating characteristic showed that the cut-off level of CD19+B cell proportion was 15.12%, with a sensitivity of 90.90%, specificity of 88.20% and an area under curve of 0.888 (95% CI 0.759 to 1.000, p=0.001).Conclusion Findings support the baseline CD19+B cell proportion could be used to predict CR to treatment with belimumab in refractory lupus nephritis patients.
Objective To characterise histological response following induction therapy in a real-world cohort of patients with proliferative lupus nephritis (LN) undergoing per-protocol repeat kidney biopsy; to assess the concordance between clinical and histological response and to identify baseline factors associated with changes in activity and chronicity indices. Methods We conducted a retrospective observational study including 20 adult patients with systemic lupus erythematosus and biopsy-proven proliferative LN who underwent a protocolised repeat kidney biopsy at 6 months (±3 months) after induction therapy. Clinical, laboratory and histopathological data were collected at both biopsy time points. Associations between baseline parameters and histological outcomes were explored. Results After a median of 7.5 months, proteinuria significantly decreased while estimated glomerular filtration rate and complement levels significantly improved. The histological activity index (AI) decreased significantly, with improvement observed in 90% of patients. Chronicity index (CI) increased in 50% of patients, without reaching statistical significance. At 6 months, 55% of patients achieved primary efficacy renal response, whereas 45% achieved histological response. Notably, discordance between clinical and histological responses was frequent: 45% of clinical responders exhibited persistent histological activity and 33% of histological responders failed to meet clinical response criteria. Lower baseline proteinuria and better baseline renal function were observed among patients with AI improvement. Likewise, patients with an increase in CI had a lower baseline CI and tended to have a better baseline renal function. Histological outcomes did not differ according to the type of immunosuppressive therapy used during induction. Conclusions In this real-world cohort of proliferative LN, substantial discordance between clinical and histological response was observed following induction therapy. While histological activity improved in most patients, chronic damage progressed in half of the cohort despite favourable clinical evolution. These findings should be interpreted as exploratory and hypothesis-generating rather than as definitive associations and highlight the need for prospective studies to define its role in personalised LN management.
OBJECTIVE:To determine whether circulating kidney injury molecule-1 (KIM-1) predicts long-term renal outcomes in lupus nephritis (LN), including relapse, progression to end-stage kidney disease (ESKD) and mortality. METHODS:This retrospective cohort study included 63 Japanese patients with biopsy-confirmed LN who were treated at Kanazawa University Hospital between 1990 and 2022. After excluding 17 patients who did not meet the eligibility criteria, 46 patients were included in the final analysis. Circulating KIM-1 levels were measured in serum samples collected at the time of renal biopsy prior to treatment or additional treatment. Patients were stratified into low-KIM-1 and high-KIM-1 groups using the median value (153 pg/mL) as the cut-off. The primary endpoints were LN relapse, ESKD and all-cause mortality. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS:During a median follow-up of 127 months, nine patients (20%) experienced relapse, four (9%) developed ESKD and six (13%) died. The high-KIM-1 group had lower baseline renal function, greater proteinuria, a higher frequency of Class IV histology and higher activity index scores. Kaplan-Meier analysis demonstrated significantly lower LN relapse-free (p=0.027; log-rank) and ESKD-free survival (p=0.049) in the high-KIM-1 group. In the multivariable Cox regression analysis, circulating KIM-1 was independently associated with LN relapse (per-IQR HR: 1.92, 95% CI 1.07 to 3.45; p=0.029). CONCLUSION:Elevated circulating KIM-1 at the time of renal biopsy was associated with adverse long-term renal outcomes in LN and independently associated with relapse, although its incremental predictive value beyond conventional clinical markers was modest. KIM-1 may support early risk stratification and individualised treatment; however, prospective validation in larger cohorts is needed.
OBJECTIVE:To identify longitudinal predictors of neuropsychiatric damage in SLE and compare predictors of organic versus all neuropsychiatric outcomes. METHODS:We studied 657 patients from the multiethnic Lupus in Minorities: Nature vs Nurture cohort (5944 person-visit observations). Organic neuropsychiatric damage (seizures, cerebrovascular accident, neuropathy, transverse myelitis) and all neuropsychiatric damage (organic plus cognitive impairment/psychosis) were defined using the Systemic Lupus International Collaborating Clinic/American College of Rheumatology Damage Index. Random survival forests with time-varying covariates modelled 173 predictors. Feature importance was assessed by permutation methods and SHapley Additive exPlanations (SHAP). RESULTS:92 patients (14.0%) had organic and 197 (30.0%) had any neuropsychiatric damage; models were trained on incident events (48 and 90, respectively). Random survival forests achieved C-indices of 0.738 (organic) and 0.775 (all neuropsychiatric damage) outperforming Cox regression. For organic damage, glucocorticoid highest ever daily dose was the strongest predictor, followed by social support deficits and retirement status, exceeding disease activity measures. Tangible material support deficits specifically dominated the social support signal. SHAP dependence analysis suggested a model-derived inflection in risk contribution between approximately 40 and 60 mg/day, with current dose contributing approximately 2.8-fold more to model-predicted risk for all neuropsychiatric damage than for organic damage alone (mean |SHAP| 0.022 vs 0.008). For the secondary outcome, physician global assessment, fatigue and pain ranked highest, suggesting distinct predictor profiles for cognitive versus organic outcomes. Social determinants of health contributed independently of clinical severity. CONCLUSIONS:In this exploratory analysis, glucocorticoid exposure and tangible social support deficits emerged as leading, potentially modifiable predictors of neuropsychiatric damage in SLE, often outranking disease activity measures, with implications for glucocorticoid stewardship, tangible-support screening and outcome-specific management. External validation in an independent contemporary cohort is required prior to clinical translation.
