Lupus Science & Medicine最新文献

Objective: Dyslipidaemia in systemic lupus erythematosus (SLE) contributes to pathogenesis and cardiovascular risk. The effect of statin therapy on SLE disease activity remains controversial. This meta-analysis systematically evaluates the impact of statins on SLE activity and inflammatory markers.

Methods: This study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A systematic literature search across multiple databases was conducted up to 13 November 2024. Study selection, data extraction and quality assessment were performed independently by two reviewers. Meta-analysis was conducted using R software, evaluating outcomes including SLE Disease Activity Index (SLEDAI), C-reactive protein (CRP), interleukin-6 (IL-6) and erythrocyte sedimentation rate (ESR).

Results: From 3596 identified records, 12 studies were included. Statins significantly reduced SLEDAI in controlled before-after studies (weighted mean difference (WMD)=-0.70, 95% CI -1.16 to -0.23; p=0.0037), but not in parallel controlled trials (WMD=-0.58, 95% CI -1.74 to 0.59; p=0.330; I² = 81.1%). Subgroup analysis showed a pronounced reduction in patients with a mean age <40 years (WMD=-1.60, 95% CI -1.98 to -1.22; p<0.001). Statins lowered CRP in both controlled before-after studies (standardised mean difference (SMD)=-0.38, 95% CI -0.73 to -0.03; p=0.032) and parallel controlled trials (SMD=-1.45, 95% CI -2.84 to -0.07; p=0.040). After excluding an outlier, the reduction in IL-6 became significant (SMD=-0.32, 95% CI -0.63 to -0.00; p=0.048). ESR was also reduced (SMD=-1.81, 95% CI -3.54 to -0.08; p=0.0406). No significant publication bias was detected.

Conclusion: Statin therapy may reduce disease activity and inflammation in SLE, with a consistent benefit observed in patients with a mean age <40 years. Significant heterogeneity underscores the need for future rigorously designed, age-stratified randomised trials to confirm these findings and define the target patient population.

Prospero registration number: CRD42025630267.

Background: Current diagnosis of antiphospholipid syndrome (APS) relies on antiphospholipid antibodies (aPL) testing, but false-positive aPL results and asymptomatic aPL carriers pose significant clinical challenges. The importance of S100A8 in thrombosis has been demonstrated, yet its potential role in APS has received little attention. This study aimed to assess serum S100A8 for APS diagnosis and risk stratification among aPL carriers.

Methods: Serum S100A8 levels were measured by ELISA in healthy controls (HCs), aPL carriers without manifestation and patients with APS. Receiver operating characteristic curves were used to evaluate the diagnostic performance of APS. Logistic regression was performed to identify independent variables associated with obstetric morbidity among female aPL carriers.

Results: The study enrolled 120 HCs, 57 aPL carriers and 114 patients with APS. Serum S100A8 levels were significantly higher in aPL carriers (median 44.3 (IQR 35.6-75.4) ng/mL, p<0.001) and patients with APS (52.8 (37.2-79.2) ng/mL, p<0.001) compared with HCs (25 (21.6-31.1) ng/mL). S100A8 showed good diagnostic accuracy for APS (area under the curve (AUC)=0.854, 95% CI 0.803 to 0.907, p<0.001), with similar performance for thrombotic APS (AUC=0.819, 95% CI 0.747 to 0.891, p<0.001) and obstetric APS (AUC=0.874, 95% CI 0.821 to 0.926, p<0.001). Multivariate logistic regression revealed that S100A8 positivity was independently associated with increased obstetric APS risk among aPL carriers (OR 3.335, 95% CI 1.010 to 11.012, p=0.048).

Conclusion: S100A8 may serve as a complementary biomarker for the diagnosis and risk stratification of APS, especially in female aPL carriers at risk of obstetric morbidity. These findings support further investigation into its clinical and mechanistic role in APS pathogenesis.

Objective: Skeletal fragility is a major comorbidity in systemic lupus erythematosus (SLE), yet the accuracy of fracture risk algorithms in this population remains uncertain. We compared the discriminative ability of Fracture Risk Assessment Tool (FRAX) and the Italian FRAX-derived tool (DeFRA) for fractures in SLE.

Methods: This is a secondary analysis of the multicentre osteoporosis and FRagility fracture Among SLE patients (FRAIL - NCT05590390) cohort that included patients with SLE who underwent dual-energy X-ray absorptiometry with vertebral fracture assessment (VFA). Vertebral fractures were confirmed by radiography. For each patient, 10-year major osteoporotic fracture probability was calculated using FRAX and DeFRA. Discrimination was assessed with receiver operating characteristic curves and DeLong's test. Operational thresholds (FRAX ≥20%, DeFRA ≥20% and 15%) were evaluated for sensitivity, specificity, predictive values and number needed to scan (NNS=1/positive predictive value). Robustness of estimates was tested using 2000 bootstrap resamples with out-of-bag evaluation.

Results: 106 patients with SLE were included in the study. Mean age was 53.6 years, 88.7% were female and 41.5% were on glucocorticoids. Morphometric vertebral fractures were identified in 23 patients (21.7%), including 15 previously unrecognised. For newly detected fractures, area under the curve (AUC) was higher for DeFRA (0.834, 95% CI 0.725 to 0.944) than FRAX (0.681, 95% CI 0.495 to 0.867; p=0.022). Similar results were observed when considering any vertebral fracture (AUC 0.902 vs 0.770; p=0.013). At operational thresholds, DeFRA ≥20% identified 9/15 new fractures (NNS=1.78) versus 7 with FRAX ≥20%, while lowering the cut-off to DeFRA ≥15% increased sensitivity (10/15 fractures, NNS=2.0) without loss of specificity. Bootstrap validation confirmed the robustness of rank ordering.

Conclusion: In SLE, DeFRA outperforms FRAX in detecting vertebral fractures and offers a clinically efficient threshold for guiding targeted VFA, with potential implications for optimising imaging strategies and glucocorticoid management.

Background: The long-term trajectories of estimated glomerular filtration rate (eGFR) and their relation to early proteinuria trajectories in biopsy-proven lupus nephritis (LN) are unclear. We aimed to identify eGFR trajectories and examine their association with 24-hour urine protein (24hUP) trajectories.

Methods: In this retrospective single-centre cohort, 215 adults with class III/IV (±V) LN were followed from the date of their initial renal biopsy. eGFR and 24hUP trajectories were modelled using latent class trajectory models, and associations with clinical and pathologic features were assessed. Multinomial logistic regression was used to identify baseline predictors of trajectory membership.

Results: Three eGFR trajectories were identified: stable (87.9%), late-decline (7.0%) and persistent-decline (5.1%). Persistent-decline patients had a higher chronicity index (p<0.01) and baseline serum creatinine (p=0.03), and a higher chronicity index independently predicted persistent-decline (OR 1.64; 95% CI 1.24 to 2.18). The late-decline group had higher baseline eGFR (p=0.03) and more frequent proteinuric flares (91% vs 25% for stable, p<0.01). Three 24hUP trajectories were identified: low-decreasing (81.5%), high-decreasing (11.4%) and high-increasing (7.1%). eGFR late/persistent-decline trajectories were associated with high-decreasing/increasing 24hUP trajectories (p<0.001). Notably, 48% of patients with declining eGFR achieved complete proteinuria response within 12 months, and 38% met criteria for complete renal response, despite long-term eGFR deterioration.

Conclusion: Distinct long-term trajectories of eGFR and proteinuria exist in LN. Short-term responses in eGFR and proteinuria may not reliably predict long-term renal outcomes, highlighting the need for more robust biomarkers to improve risk stratification and management in LN.

Objectives: This study aims to compare the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus (CP) volume and perivascular space (PVS) volume across different subtypes of neuropsychiatric systemic lupus erythematosus (NPSLE) in order to gain a deeper understanding of brain-immune interfacing dysfunction and neuroinflammation in these patients.

Methods: A total of 157 patients with SLE (57 non-NPSLE, 57 inflammatory NPSLE and 43 ischaemic NPSLE) and 60 healthy controls (HCs) were enrolled. CP and PVS morphometry were assessed using T1-weighted and T2-weighted images. The DTI-ALPS index was computed to evaluate diffusivity along the x, y and z axes in the lateral ventricle body. Between-group differences in DTI-ALPS and CP/PVS volumes were analysed using analysis of covariance. Receiver operating characteristic (ROC) curve analysis was conducted to differentiate NPSLE and its inflammatory subtype from non-NPSLE. Correlations between imaging data and clinical variables were also examined.

Results: The DTI-ALPS index is significantly reduced in NPSLE compared with HCs and patients without NPSLE (L: F=10.924, p<0.001; R: F=5.110, p=0.017), particularly in those with inflammatory subtypes. CP volume is significantly higher in patients with SLE than in HCs (L: F=22.273, p<0.001; R: F=21.176, p<0.001). ROC analysis shows moderate diagnostic accuracy for distinguishing non-NPSLE from NPSLE, as well as non-NPSLE from inflammatory NPSLE, when combining the DTI-ALPS index and CP volume (L: area under the curve (AUC)=0.764; R: AUC=0.728). The DTI-ALPS index negatively correlates with ipsilateral CP volume (L: r=-0.315; p<0.001) and positively with Montreal Cognitive Assessment scores (L: r=0.339; p<0.001).

Conclusion: In conclusion, the DTI-ALPS index and CP volume demonstrate significant potential as neuroimaging biomarkers for NPSLE. They hold promise for differentiating between NPSLE subtypes and shedding light on the underlying mechanisms of central nervous system damage.

Objectives: This study aimed to evaluate the epidemiology and predisposing factors for malignancy in lupus nephritis (LN).

Methods: This retrospective cohort study included 290 patients diagnosed with LN from 1969 to 2023. Demographic and clinical variables were analysed using the Mann-Whitney U test and Fisher's test. To identify predictors of cancer development, univariate logistic regression analysis was conducted.

Results: Over a median follow-up period of 15 years (IQR 6-25), 27 malignancies were diagnosed (prevalence 9.3%, incidence 6.08 per 1000 person-years), 22.2% affecting the urinary tract and 33.3% the skin. Cancer diagnoses were evenly distributed across the decades of observation and 85.2% occurred during a quiescent phase of LN. Mortality was significantly higher in patients with malignancies compared with those without (25.9% vs 6.9%, p=0.012). Patients with malignancies were significantly older at LN diagnosis (31.6 vs 28.7 years, p=0.035) and at the end of follow-up (58.1 years vs 45.2 years, p<0.001), were more frequently smokers (84.6% vs 37.7%, p=0.001) and exposed to higher cumulative doses of glucocorticoids (37.0 g vs 23.7 g, p=0.031). Univariate analysis identified smoking (OR 9.081, 95% CI 1.921 to 42.937; p<0.001), older age (OR 1.058, 95% CI 1.028 to 1.089; p<0.001) and higher proteinuria at LN onset (OR 1.126, 95% CI:1.024 to 1.237; p=0.016) as significant risk factors for malignancy.

Conclusion: In patients with LN, the considerable risk of malignancy and its associated increase in mortality necessitate long-term monitoring, regardless of activity phase and disease duration. Smoking remains a major risk factor in this population, and its cessation should be actively promoted as part of patient care.

Objective: SLE is a multifaceted chronic inflammatory disorder characterised by a dysregulated immune response that involves various organ systems, with significant implications stemming from the type I interferon (IFN) signalling pathway in its pathogenesis. This study aimed to elucidate the contributory role of the IFN-induced protein 44-like (IFI44L) gene in SLE progression and to investigate its transcriptional regulatory mechanisms.

Methods: We quantified IFI44L expression in peripheral blood mononuclear cells of patients with SLE through quantitative PCR (qPCR), and established an in vitro THP-1 cell model overexpressing IFI44L to assess its impact under IFN-α exposure using Cell Counting Kit-8 assays and flow cytometry. Additionally, we generated Ifi44l knockout mice and Pristane-induced lupus mice to evaluate the influence of IFI44L on immune phenotypes and organ functionality.

Results: Our findings demonstrated that IFI44L is significantly expressed in CD3⁺ and CD14⁺ lymphocytes in patients with SLE, and under heightened IFN conditions, it plays a role in promoting cell proliferation while inhibiting apoptosis. Importantly, Ifi44l knockout mice exhibited ameliorated clinicopathological features of lupus, showing reduced haematological and renal damage. Furthermore, we identified c-Jun as a transcriptional factor that directly targets the IFI44L promoter, specifically activated by IFN-α in CD14⁺ lymphocytes.

Conclusions: Our research indicates that IFN-α enhances IFI44L expression via c-Jun, underscoring its critical role in the pathogenesis of SLE and suggesting potential pathways for therapeutic intervention.

Objective: To evaluate the efficacy, safety and predictive factors of belimumab (BEL)-based triple therapy in proliferative lupus nephritis (LN) in real-world settings.

Methods: We conducted a multicentre, retrospective study including patients with proliferative LN (new-onset or relapsing) who initiated BEL within 6 months of a renal flare, in combination with standard-of-care.

Results: 49 patients were included (mean age 37 years; 85.7% female; 67.3% Caucasian). The median time from renal flare to BEL initiation was 1 month (IQR 0-3). By 12 months, 67.3% achieved complete renal response (CRR), 75.5% primary efficacy renal response (PERR) and 83.7% at least partial renal response. Median proteinuria declined from 2.7 g/day to 0.49 g/day, with parallel improvement in estimated glomerular filtration rate (71 to 78 mL/min/1.73 m²). Patients with baseline proteinuria <3 g/day achieved significantly higher CRR (78.1% vs 47.1%; p=0.027) and PERR (84.4% vs 58.8%; p=0.048) rates.The mean glucocorticoid (GC) dose decreased from 31.7 mg/day at baseline to 3.5 mg/day at 12 months, and 26.1% of patients achieved complete GC withdrawal. Extrarenal disease activity was present in 81.6% of patients at baseline, predominantly articular and mucocutaneous, with clinically meaningful improvement in 80% during follow-up. At 12 months, 40.8% met remission by Definition Of Remission In Systemic Lupus Erythematosus (DORIS) criteria and 46.9% attained Lupus Low Disease Activity State (LLDAS). Renal treatment failure occurred in 16.3% and renal relapse in 4.1%. Adverse events were mild, and no serious BEL-related events were observed.

Conclusion: BEL-based triple therapy is effective and safe in proliferative LN, achieving high renal and extrarenal response rates, substantial GC-sparing and treat-to-target outcomes in real-world practice.

Objective: To compare preconception disease-activity indices-systemic lupus erythematosus Disease Activity Score low disease activity (SLE-DAS LDA), lupus low disease activity state (LLDAS) and SLE-DAS remission-with Definitions of Remission in SLE (DORIS) remission in predicting adverse maternal and fetal outcomes among pregnant women with SLE.

Methods: This retrospective cohort study included 202 pregnancies in 196 women with SLE managed at Shenzhen People's Hospital between January 2017 and December 2024. Preconception disease activity was categorised using SLE-DAS, LLDAS and DORIS remission criteria. Main outcomes were maternal flares and fetal outcomes, including spontaneous abortion, therapeutic abortion, total fetal loss, preterm delivery and small for gestational age (SGA). Predictive accuracies of indices were compared.

Results: Preconceptionally, 127 pregnancies (62.8%) met LLDAS, 131 (64.9%) met SLE-DAS LDA and 78 (38.6%) achieved DORIS remission. Compared with higher disease activity, SLE-DAS LDA was associated with fewer maternal flares (22.1% vs 45.1%) and therapeutic abortions (6.4% vs 15.7%). LLDAS was associated with lower rates of flare (21.3% vs 45.3%), therapeutic abortion (7.9% vs 17.3%), total fetal loss (19.7% vs 34.2%) and preterm delivery (22.0% vs 25.3%). SLE-DAS and DORIS remission performed similarly for maternal outcomes, while DORIS remission correlated more strongly with favourable fetal outcomes, including lower total fetal loss (15.4% vs 31.5%), preterm delivery (15.4% vs 28.2%) and SGA (9.0% vs 19.4%). Multivariable analyses confirmed that achieving these disease-activity states preconception independently protected against total fetal loss, maternal flare and therapeutic abortion. LLDAS was the best overall predictor, while SLE-DAS LDA was the most attainable and predictive for maternal complications.

Conclusion: SLE-DAS LDA effectively predicts maternal complication, while LLDAS better identifies fetal risk. Remission offers similar protection but is less attainable, suggesting LDA suffices for conception planning. Optimising preconception disease control remains essential and warrants multicentre validation.

Objectives: Both telitacicept and belimumab are approved for treating active systemic lupus erythematosus (SLE) in China. However, the economic value of these two drugs is unclear. Therefore, this study aims to evaluate the cost-effectiveness of telitacicept versus belimumab in SLE from the perspective of Chinese society.

Methods: The network meta-analysis (NMA) and cost-effectiveness analysis included the efficacy and safety of patients from five randomised clinical trials. A microsimulation model was constructed to compare the cost-effectiveness of telitacicept versus belimumab in SLE. The model integrated short-term efficacy and long-term prognosis to simulate the patient's lifetime. Outcome measures included life years (LYs), quality-adjusted LYs (QALYs), total healthcare costs and the incremental cost-effectiveness ratio (ICER). The robustness of the model was assessed through sensitivity analyses.

Results: The NMA suggested the response rate risk ratios (RRs) of telitacicept compared with belimumab were 1.200 (95% CI 0.760 to 1.910). When this RR was used as the model input, the results of the baseline analysis showed an increase in the effectiveness of 0.506 QALYs and an increase in the total cost of US$3026 for telitacicept as compared with belimumab, with an ICER of US$5984 per QALY gained. At a willingness-to-pay (WTP) threshold of US$40 344 per QALY, the probability that telitacicept would be cost-effective compared with belimumab was 99.1%.

Conclusion: Although the comparative efficacy between telitacicept and belimumab remains statistically inconclusive, cost-effectiveness modelling suggests that telitacicept plus standard therapy is likely to be a cost-effective treatment option for patients with SLE in China under current WTP thresholds.