Lupus Science & Medicine最新文献

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.

Objective: To assess the clinical relevance of concurrent measurement of anti-chromatin antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies using a multiplex immunoassay in systemic lupus erythematosus (SLE), focusing on their association with organ-specific manifestations and disease activity.

Methods: Adult patients diagnosed with SLE based on the 2012 Systemic Lupus International Collaborating Clinics or 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology criteria and followed in our university hospital between 2015 and 2019 were retrospectively included if they had at least one positive detection of anti-dsDNA and/or anti-chromatin result by a multiplex immunoassay, with clinical data available within the 30 days before or after testing. Clinical manifestations, treatments, laboratory parameters and disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K)) were compared using mixed models and correlation coefficients.

Results: 98 patients (88% women; median age 42 (IQR: 35-50)) had 677 antibody evaluations. Levels of anti-dsDNA and anti-chromatin antibodies were correlated (r=0.39, 95% CI 0.21 to 0.55). Results were discordant in 59 patients (60%), representing 215 assessments (32%), with anti-chromatin antibodies being detected without anti-dsDNA in 111/677 samples (16%). Rise in anti-dsDNA antibody titre was associated with cutaneous (OR 2.29, 95% CI 1.43 to 3.68) and musculoskeletal involvement (OR 1.29, 95% CI 1.02 to 1.64), while anti-chromatin antibody increase was linked to neuropsychiatric manifestations (OR 1.54, 95% CI 1.03 to 2.29). The increase of either antibody titre was independently associated with proteinuria >0.5 g/24 hours (anti-dsDNA antibody: OR 1.17, 95% CI 1.11 to 2.74; anti-chromatin antibody: OR 1.71, 95% CI 1.02 to 2.87). Correlation with SLEDAI-2K was moderate for anti-dsDNA (r=0.55; 95% CI 0.39 to 0.67), and weaker for anti-chromatin (r=0.32; 95% CI 0.16 to 0.51]).

Conclusions: Concomitant measurement of anti-dsDNA and anti-chromatin antibodies using a multiplex immunoassay system brings complementary information for diagnosis and monitoring of SLE. Both antibodies are associated with disease activity and renal involvement, while anti-chromatin antibodies are associated with neuropsychiatric flares. Anti-chromatin antibodies provide additional diagnostic value, particularly in the absence of anti-dsDNA positivity that was observed in 16% of our cohort.

Objective: To systematically identify herbal supplements with immunostimulatory properties that may trigger or exacerbate autoimmune skin diseases.

Methods: We conducted a systematic scoping review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. PubMed was searched for studies published before 3 August 2025 using predefined immune, herbal supplement, autoimmune, skin and interferon terms. Articles in English that described immunostimulatory effects of herbal supplements in vitro, in model organisms or in human/clinical studies were included. Data were extracted by four reviewers and synthesised qualitatively, with herbs categorised according to levels of supporting evidence for their immunostimulatory properties. A subgroup of herbs with the strongest evidence was identified based on predefined criteria.

Results: From 11 819 unique articles screened, 469 studies met inclusion criteria. Across these, 227 distinct immunostimulatory herbal supplements were identified: 79 supported by human studies, 145 by model organism studies and 148 by in vitro studies. 15 herbs demonstrated the most robust evidence across all three evidence types, supported by more than five single-ingredient studies or more than 25 references overall. These included alfalfa, ashwagandha, astragalus, chlorella, echinacea, garlic, ginseng, green tea extract, Indian mulberry, liquorice, mistletoe, reishi mushroom, skullcap, spirulina and tinospora. These herbs were widely marketed for 'immune support' and shared proinflammatory mechanisms, including toll-like receptor activation, NF-κB/MAPK signalling and increased production of inflammatory cytokines including IL-1β, IL-6, TNF-α, IL-12 and IFN-γ.

Conclusions: We identified 227 herbal supplements with immunostimulatory properties, of which 15 were most strongly supported by the evidence. This article may serve as a reference to help clinicians counsel patients with autoimmune skin diseases on the risks associated with use of specific herbal supplements.

Objective: To characterise the age-related impact of organ damage patterns on health-related quality of life (HRQoL) in patients with SLE and to identify specific damage patterns affecting physical and mental health outcomes across different age groups.

Methods: In this cross-sectional study, 1149 patients with SLE from the Asia Pacific Lupus Collaboration cohort were stratified by age. HRQoL was assessed using the Short Form-36 questionnaire. Clinical characteristics and organ damage (Systemic Lupus International Collaborating Clinics (SLICC) Damage Index) were evaluated. Multiple linear regression analyses identified factors associated with the Physical (PCS) and Mental Component Summary (MCS) scores.

Results: Significant age-related differences were observed in physical HRQoL, with the age group ≥50 years showing lower PCS scores (median 52.6) than the age groups <20 years (56.9) and 20-50 years (57.5) (p<0.001). In multivariable models, higher SLICC Damage Index (β=-1.39), lower educational attainment (β=-7.02) and prednisolone use (β=-1.85) were independently associated with lower PCS scores. MCS scores were positively associated with male gender (β=4.40) and secondary education (β=2.46), but negatively impacted by higher damage index (β=-0.90) and cyclophosphamide use (β=-5.44). Specific damage patterns, such as avascular necrosis, particularly impaired bodily pain and physical functioning domains.

Conclusion: Age-related differences in SLE predominantly affect physical rather than mental aspects of HRQoL. Cumulative organ damage remains a central modifiable factor associated with poorer outcomes across all ages. These findings emphasise the importance of age-specific management strategies and early damage prevention to optimise long-term HRQoL in patients with SLE.