Lupus Science & Medicine最新文献

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.

Objective: This study aimed to evaluate the prevalence and predictors of cardiovascular disease (CVD), chronic kidney disease (CKD) and osteoporosis among patients with systemic lupus erythematosus (SLE) in Punjab, Pakistan.

Methods: A cross-sectional analysis of a prospective registry was conducted using data from the Punjab Lupus Registry between January 2020 and December 2024. Adults (≥18 years) fulfilling the 2019 European League Against Rheumatism/American College of Rheumatology SLE classification criteria were included. Of 536 registered patients, 482 with complete data were analysed. Comorbidities were physician-confirmed, and disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Associations between disease duration and comorbidities were examined using χ² tests for trend, while predictors of comorbidity burden were identified using multivariable Poisson regression with robust error variance.

Results: Among 482 patients (mean age 39.6±12.4 years; 67.2% female), 43.6% had at least one comorbidity and 15.1% had multimorbidity. The prevalence of CVD, CKD and osteoporosis increased with disease duration: 12.3%, 10.6% and 8.2% in <5 years versus 39.6%, 28.9% and 25.4% in >10 years (p<0.001). Older age (adjusted prevalence ratios (aPR) 1.31 per 10 years), longer disease duration (aPR 1.22 per 5 years), corticosteroid use (aPR 1.33), smoking (aPR 1.26) and low socioeconomic status (aPR 1.38) were independent predictors, while hydroxychloroquine use was protective (aPR 0.78). Patients with comorbidities had higher disease activity (SLEDAI-2K 6.9 vs 5.6, p=0.009) and greater organ damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index 2.4 vs 1.3, p<0.001).

Conclusion: Comorbidities are common in SLE and increase with age and disease duration, underscoring the need for early, integrated management to improve outcomes.

Objectives: This retrospective study aims to characterise the epidemiological features of systemic lupus erythematosus (SLE) concomitant with chronic spontaneous urticaria (CSU), examines the correlation between CSU occurrence and lupus disease activity, and identifies comorbidity patterns and risk factors associated with SLE-CSU.

Methods: A total of 40 SLE patients with concomitant CSU and 160 age-matched and sex-matched SLE controls without CSU were included. The Mann-Whitney U-test was used to assess disease activity at SLE onset in both groups. A Wilcoxon signed-rank test was conducted to compare the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores before and after CSU onset in patients with SLE. χ² tests were applied to evaluate differences in SLE activity grading, clinical manifestations, laboratory findings and treatments between patients with SLE with and without CSU. In addition, univariate and multivariate logistic regression analyses were performed to identify risk factors for CSU development in patients with SLE.

Results: Wilcoxon signed-rank tests revealed that in the SLE-CSU group, the occurrence of CSU did not result in an increase of SLEDAI scores. Univariate analysis revealed significant differences between the SLE-CSU and SLE-only groups in the presence of cylindruria, elevated IgM, IgA, IgG, serositis, mucosal ulcers and anti-Pm-Scl antibodies (p<0.05). Multivariate logistic regression analysis identified cylindruria (OR: 6.152, CI 2.352 to 16.093, p＜0.001), elevated IgA (OR: 7.598, CI 1.194 to 48.368, p=0.032), elevated IgG (OR: 3.252, CI 1.331 to 7.946, p=0.010) and mucosal ulcers (OR: 3.838, CI 1.166 to 12.637, p=0.027) as independent risk factors for CSU occurrence in patients with SLE.

Conclusion: The presence of CSU in patients with SLE does not necessarily indicate increased lupus activity. Rather, cylindruria, mucosal ulcers and elevated IgA and IgG levels were identified as independent risk factors for CSU in patients with SLE.

Objective: To evaluate the efficacy of mepacrine (MC) as an add-on therapy in patients with SLE unresponsive to hydroxychloroquine (HCQ)-containing regimens at 6 months after MC introduction.

Methods: Observational study using routine clinical care data of patients from the Lupus-Cruces cohort. All of them received therapy with HCQ and prednisone at baseline. Two groups of initial therapy were compared: single therapy (ST; HCQ + prednisone) and multiple therapy (MT; additional immunosuppressives or biologics). Achieving the definition of remission in SLE (DORIS) at 6 months was the main outcome. Prednisone tapering and MC side effects and discontinuation were also analysed. A logistic regression was performed in search of clinical predictors of response.

Results: 106 different episodes were included (ST=56, MT=50). The mean SLE Disease Activity Index (SLEDAI) at baseline was 6.7, with a mean prednisone dose of 6 mg/day. DORIS remission at 6 months was 71% for the complete cohort (ST 79% vs MT 62%, p=0.06). SLEDAI reduction at 6 months was similar in both groups (mean 4.6 points in the ST group vs 5 in the MT group, p=0.5). The reduction at 6 months was also similar (mean 1.75 mg/day in the ST group vs 1.69 mg/day in the MT group, p=0.9). The most frequent reason for MC discontinuation was improvement (45%). Adverse effects were reported in 17% patients.

Conclusions: MC is a useful therapy in mild-moderate active SLE. Using MC as the first drug after the failure of glucocorticoids and HCQ is the best option; however, the addition of MC to a multidrug regimen can also be of help.