Lupus Science & Medicine最新文献

Background: Anti-C1q autoantibodies can disrupt normal complement function, contributing to the formation of pathogenic immune complexes and end-organ damage. Although their role in SLE is well-established, their detection rate and clinical relevance across a broader spectrum of diseases remain insufficiently characterised. This study aimed to investigate the distribution of abnormal anti-C1q levels in the population and examine their associations with age, sex and specific clinical subtypes.

Methods: This retrospective study included patients who underwent anti-C1q testing at our hospital between September 2020 and September 2023. The primary outcome was the detection rate of abnormal anti-C1q levels (>10 U/mL) categorised by patient sex, age and disease diagnosis. One-way and two-way fixed-effect models were used to assess associations between odds of abnormal antibody levels and demographic factors. Multivariate logistic regression was performed to identify disease-specific correlates.

Results: Among 15 363 patients (median (IQR) age, 38 (28-53) years; 79.02% female; 52.19% aged <40 years) representing 67 distinct diagnoses, 7.88% showed abnormal anti-C1q levels. Female sex and younger age showed higher median anti-C1q levels and a greater proportion of abnormal results. SLE subtypes showed the highest detection rate of abnormal anti-C1q levels, with SLE without severe complications (853 of 3760, 22.69%) and lupus nephritis (88 of 294, 29.93%) being the most obvious. Lupus haematological and encephalopathic manifestations were associated with elevated antibody levels. Additionally, autoimmune cirrhosis (7 of 59, 11.86%) and systemic sclerosis (19 of 165, 11.52%) also showed high detection rates of abnormal anti-C1q levels. Both univariate and multivariate analyses indicated that male sex and younger age were significantly associated with increased odds of abnormal anti-C1q levels.

Conclusion: Elevations in anti-C1q levels extend beyond SLE and are influenced by both demographic factors and specific disease phenotypes. Male sex and younger age emerged as significant predictors of abnormal anti-C1q status. Our findings underscore the potential utility of anti-C1q testing for improving diagnostic precision and risk stratification across a wide range of clinical conditions.

Objective: To evaluate multiple-ascending doses of enpatoran, a selective toll-like receptor 7/8 (TLR7/8) inhibitor with the potential to modulate processes central to lupus pathophysiology, in patients with systemic and cutaneous lupus erythematosus (SLE/CLE).

Methods: In this randomised, double-blind, placebo-controlled phase Ib trial (NCT04647708), patients with active SLE/CLE were randomised 3:1 to enpatoran or placebo across four cohorts. Treatment duration was 12/24 weeks. All patients had a 2-week safety follow-up. The primary endpoint was safety and tolerability. Secondary endpoints included pharmacokinetics (PK) and clinical response. Change in lupus biomarkers, including interferon gene signature (IFN-GS), was an exploratory endpoint.

Results: 25 patients received placebo (n=6) or enpatoran (n=19); 80% were female, all were white, and the median age was 44 years. By week 12, treatment-emergent adverse events (TEAEs) were reported by 42% of patients across the four enpatoran dose groups and 33% of placebo-treated patients. Enpatoran remained well tolerated to week 24. Most TEAEs (96%) were mild or moderate in severity. There were no serious TEAEs. Enpatoran PK was dose proportional, with peak concentration reached 1-2 hours postdose and an apparent half-life of 6-10 hours across doses. Greater reductions in Systemic Lupus Erythematosus Disease Activity Index 2000, Physician's Global Assessment and 28-joint count were observed at week 24 with enpatoran versus placebo. Rapid, dose-dependent and reversible suppression of IFN-GS was observed.

Conclusions: Enpatoran was well tolerated and demonstrated favourable safety and PK profiles in patients with SLE and CLE. Although preliminary, the SLE disease activity and biomarker results support the therapeutic targeting of TLR7/8 for lupus.

Trial registration number: NCT04647708.

Objective: Small fibre neuropathy (SFN) is an under-recognised complication of SLE that contributes to chronic pain and reduced quality of life. We assessed the utility of corneal confocal microscopy (CCM) for identifying small fibre damage in SLE in relation to disease activity, neuropathic pain and quality of life.

Methods: Participants with SLE and healthy controls underwent CCM to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), corneal nerve fibre tortuosity (CNFT), inferior whorl length (IWL), Douleur Neuropathique 4 (DN4) Score, vibration perception threshold (VPT) and sudomotor function.

Results: Participants with SLE (n=59; age 38.6±9.6 years; mean Systemic Lupus Erythematosus Disease Activity Index Score 3.4±4.2) had significantly lower CNBD (41.5±21.3 vs 72.1±29.4 branches/mm², p=0.0001) and CNFL (18.5±4.3 vs 24.2±4.4 mm/mm², p=0.0001) but comparable CNFD (31.7±7.1 and 34.0±6.9 fibres/mm², respectively, p=0.25), CNFT (15.0±4.0 and 14.3±3.1, respectively, p=0.55), and IWL (38.5±8.0 and 35.6±5.9 mm/mm², respectively, p=0.16) compared with healthy controls (n=17). Patients with SLE had a DN4 Score of 3.5±2.5 and elevated VPT (4.1±3.3 vs 2.8±0.7 V, p<0.01) but comparable sudomotor function of the hands and feet (p=0.28-0.42). Active SLE was associated with a lower CNBD/CNFD ratio (p<0.05). Patients with SLE associated with sustained neuropathic pain (17.2%) had significantly lower CNFD, CNFL and IWL than those with transient (p<0.05-0.0001) and recurrent (p<0.05-0.01) pain but comparable VPT (p=0.27) and sudomotor function (p=0.14). Reduced CNFL was associated with bodily pain, affecting quality of life (p<0.05).

Conclusion: This study demonstrates that CCM detects peripheral neurodegeneration in patients with SLE, which relates to disease activity, sustained neuropathic pain and quality of life. CCM may serve as a rapid non-invasive neuroimaging technique to identify SFN in SLE.

Background: Lupus nephritis (LN) is the most serious complication of SLE. Interstitial fibrosis is the dominant pathological change of renal injury in LN. Enhanced histone deacetylase 3 (HDAC3) positively correlates with renal interstitial fibrosis (RIF). Our study objective was to explore the accurate role and mechanism of HDAC3 in the RIF of LN.

Methods: To knock down HDAC3, Murphy Roths large (MRL)/wt and MRL/MpJ-Faslpr/J (MRL/lpr mice were injected with lentiviral short hairpin RNAs. Human renal proximal tubular epithelial cells (HK-2 cells) were treated with serum from patients with LN to establish an LN cell model. Renal histopathological change was assessed by H&E, Masson and Sirius red staining. Cell viability was determined using Cell Counting Kit-8 (CCK-8) kits. Inflammation cytokine determination was conducted employing ELISA assays. Protein expression was detected by western blot, and immunohistochemical and immunofluorescence staining. Gene densities were analysed by quantitative real-time PCR assays. Co-immunoprecipitation analysis validated the interactions of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1).

Results: HDAC3 levels were increased in the serum and kidney tissues of patients with SLE and LN, and the LN group posted the highest level. HDAC3 knockdown ameliorated RIF, oxidative stress, inflammation and ferroptosis in kidney tissues of MRL/lpr mice. Moreover, HDAC3 inhibition repressed the inflammatory and oxidative reactions, fibrosis and ferroptosis in LN-serum-induced HK-2 cells. Further, HDAC3 knockdown could inhibit the Keap1-Nrf2 interaction to trigger Nrf2 activation.

Conclusion: HDAC3 inhibition relieved RIF, oxidative stress, inflammation and ferroptosis by upregulating Nrf2 in the mice and cell models of LN.

Objective: To evaluate the effect of early belimumab administration on disease progression in patients with early active SLE.

Methods: This multicentre observational study included patients with early active SLE, defined as being diagnosed ≤12 months from enrolment in the study, displaying ≤2 clinical European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) 2019 criteria, without major organ involvement but with active serology. Patients were receiving glucocorticoids and hydroxychloroquine as standard of care (SoC) and either belimumab (BEL group) or standard immunosuppression (SoC group). Patients were followed up for 12 months, and accrual of new EULAR/ACR criteria served as a marker of disease progression. Kaplan-Meier survival analysis and log-rank tests were applied to assess differences in criteria-free survival between groups, while Cox regression compared the lag time to criteria accrual.

Results: 69 patients were included (BEL=33 and SoC=36). Patients receiving early BEL accrued fewer events per 100 patient-years compared with SoC (2.78 vs 12.12, p=0.035). Criteria-free survival was longer in the BEL group (log-rank p=0.04), with a mean time-to-event of 11.8±1.07 months versus 10.3±3.33 months in the SoC group (Cox regression, p=0.027). Early BEL was associated with a sixfold higher likelihood of achieving glucocorticoid (GC) discontinuation at 12 months as compared with patients on hydroxychloroquine (HCQ) and GC alone (OR 6.67, p=0.0014).

Conclusions: Early administration of BEL in active SLE significantly delays disease progression and promotes GC withdrawal. These findings are more striking when limiting SoC to HCQ and GC and underscore the potential of early biologic intervention to modify disease course. Further validation in larger, prospective studies is warranted.

Objective: Peer mentoring has been shown to be an effective intervention for chronic conditions with evidence to suggest that it might improve health-related bodily pain among African American women living with systemic lupus erythematosus (SLE). However, there is a lack of evidence to describe the intervention impact when adjusting for self-management of SLE. The present work aims to determine whether greater patient activation is associated with greater reductions in pain overall and within intervention groups.

Methods: Data were used from the Peer Approaches to Lupus Self-Management study, a randomised controlled trial designed to determine the efficacy of peer mentorship in African American women with SLE. A total of 274 participants were randomised to an intervention (mentorship) or control (non-mentorship) arms. Data were collected on self-reported Lupus Quality of Life questionnaire for bodily pain and Patient Activation Measure (PAM). Linear mixed models and multivariable linear mixed models were fit to assess the intervention and impact of PAM on bodily pain over time.

Results: Increased patient activation was significantly associated with greater reductions in bodily pain (b=-0.13, p=0.019); however, there was no significant difference in intervention group over the study period between the intervention and control groups CONCLUSION: Patient self-management can have a significant effect on bodily pain for SLE patients. Future work aims to consider strategies which address patient activation as a mechanism for reducing pain and improving quality of life.

Trial registration number: NCT03734055.

Objective: Macrophage activation syndrome (MAS), a subtype of secondary haemophagocytic lymphohistiocytosis (HLH), is a rare and life-threatening complication of rheumatoid diseases. However, the prognostic factors in adult MAS patients are still not fully elucidated, which need further investigation.

Methods: We conducted a retrospective study of adult MAS inpatients between January 2016 and January 2024. In accordance with HLH-2004 criteria, 116 patients were eventually enrolled in this study. Clinical manifestations, laboratory data, treatments and outcomes had been recorded. Influence factors associated with prognosis were analysed using logistic regression models.

Results: Seventeen of 116 (14.7%) patients died during hospitalisation. Further multivariate analysis suggested that admission ferritin <1350 ng/mL (OR=5.387, 95% CI 1.203 to 24.127, p=0.034), platelets (PLT) ≤30×10⁹/L (OR=5.387, 95% CI 1.203 to 24.127, p=0.028), alanine aminotransferase (ALT) ≥275 U/L (OR=5.732, 95% CI 1.167 to 28.167, p=0.032), central nervous system (CNS) involvement (OR=11.268, 95% CI 1.353 to 93.851, p=0.025) and procalcitonin (PCT) >0.9 ng/mL (OR=11.224, 95% CI 2.019 to 62.381, p=0.006) were potential prognostic factors for mortality of adult MAS patients.

Conclusion: Our results indicated that adult MAS patients with lower ferritin levels at admission, lower PLT counts, elevated ALT, CNS involvement and more active infection were associated with an unfavourable prognosis.

Objective: Glomerular immune complex deposition plays a central role in lupus nephritis (LN), but the prognostic relevance of individual immunoglobulin components remains unclear. This study aimed to investigate the clinical impact of glomerular immunoglobulin M (IgM) deposition intensity on patient outcomes.

Methods: This retrospective cohort study analysed 952 biopsy-proven LN patients (1996-2019) from the First Affiliated Hospital of Sun Yat-sen University. A semiquantitative scoring system stratified glomerular immunoglobulin G (IgG), immunoglobulin A (IgA), IgM, complement 3 (C3) and complement component 1q (C1q) deposition into low (-/+) and high (++ to ++++) groups. The primary outcome was a composite of doubling of serum creatinine from baseline or the development of end-stage renal disease (ESRD). The secondary outcome was all-cause mortality. A multivariable Cox regression model was used to adjust for baseline clinical and pathological factors.

Results: Among the studied immune complexes, only high glomerular IgM deposition was significantly associated with adverse renal outcomes (p=0.025). These patients had higher baseline Systemic Lupus Erythematosus Disease Activity Index scores (SLEDAI) (16 (12-20) vs 15 (12-18), p<0.001), more severe histopathological features (including proliferative glomerulonephritis, endocapillary hypercellularity, leucocyte infiltration and microthrombi), and profound complement activation (lower median serum C3 and complement 4 (C4) levels, both p<0.05). High glomerular IgM deposition also correlated with high IgA (r=0.48) and C3 (r=0.40) deposition (both p<0.01). Multivariable analysis revealed that high glomerular IgM deposition remained an independent predictor of renal progression (adjusted HR=1.485, 95% CI 1.040 to 2.119, p=0.029).

Conclusion: High glomerular IgM deposition emerged as an independent prognostic marker for adverse renal outcomes in LN, potentially outperforming other individual immune complexes. These findings highlight the pathogenic significance of IgM in LN and support its value in risk stratification and treatment guidance.

Objective: Antiphospholipid syndrome (APS) is a rare autoimmune condition characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. Despite the publication of updated American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria in 2023, persistent diagnostic and therapeutic challenges remain. This qualitative study, conducted within the European Reference Network for Connective Tissue and Musculoskeletal Diseases, ReCONNET, aimed to map stakeholder-identified gaps in APS care across Europe to inform subsequent quantitative prioritisation.

Methods: Between February and April 2025, we conducted 16 semistructured interviews with purposively sampled stakeholders (clinicians across different specialties-rheumatologists, haematologists, obstetricians, neurologists, general practitioners, paediatricians, researchers and translational scientists, health systems and policy professionals, laboratory medicine experts, pharmaceutical trialists, patient and research nurses, medical students and trainees). Transcripts were thematically analysed and categorised into three domains: clinical, systemic and educational/research-related unmet needs.

Results: Over 85% of stakeholders cited delayed diagnosis as a major barrier. Eleven participants highlighted limitations of the current classification criteria in capturing all the clinical settings of APS. 75% (12 out of 16) identified lack of access to multidisciplinary teams as a barrier to optimal care. Nine respondents reported that warfarin remains the mainstay of therapy despite challenges in adherence and monitoring. Twelve stakeholders emphasised the need for integration across national or European APS registries and insufficient integration in rare disease policy frameworks. Gaps in undergraduate and postgraduate education were universally reported, with 100% of educational stakeholders noting minimal curricular exposure to APS.

Conclusion: APS remains underdiagnosed, inconsistently managed and inadequately represented in both policy and education. This study identifies quantifiable stakeholder-perceived gaps that will inform the design of Europe-wide standardised, multidisciplinary strategies to improve APS care and research infrastructure within the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases and similar networks.

Background: SLE is a chronic autoimmune disease with heterogeneous manifestations and variable outcomes. Geographic factors such as rural residence may influence disease severity, access to care and treatment adherence, yet evidence remains fragmented. This systematic review aimed to evaluate the impact of rurality on clinical outcomes in adults with SLE.

Methods: We systematically searched PubMed, Embase and Web of Science for observational studies published up to May 2025 that assessed the association between rural residence and clinical outcomes in SLE. Eligible studies included adult patients with SLE and reported at least one relevant outcome stratified by rurality. Using the Newcastle-Ottawa Scale, data were extracted on study characteristics, definitions of rurality, outcome domains and risk of bias. Due to heterogeneity in study design and outcomes, a narrative synthesis was conducted.

Results: Eight studies, including over 34 000 participants from the USA, Greece, China, Egypt, Puerto Rico and Latin America (Grupo Latino Americano de Estudio del Lupus cohort), met inclusion criteria. Definitions of rurality varied widely, encompassing administrative classifications, demographic thresholds and self-reported residence. Rural residence was often associated with delayed diagnosis, higher disease activity, lower physical quality of life, increased hospital readmissions and poorer medication adherence. Survival findings were mixed, and one study found no rural disadvantage where specialised care was available. Methodological quality was generally moderate to high.

Conclusion: Across diverse settings, rural SLE populations frequently experience worse outcomes, although this is not universal and appears to be strongly influenced by structural disadvantages rather than geography alone. Standardised definitions of rurality and multidimensional measurement approaches are needed to improve comparability and guide effective interventions. Targeted strategies-such as telemedicine, outreach programmes and policies addressing healthcare access-may help reduce inequities in SLE care.