Lupus Science & Medicine最新文献

Objective: To evaluate the feasibility, usability and acceptability of implementing a treat-to-target (T2T) strategy supported by a Clinical Decision Support System (CDSS), in routine SLE outpatient care.

Methods: A 24-week, non-randomised, multicentre, clustered pilot study was conducted across four rheumatology outpatient centres. Adult patients with SLE were allocated by centre to either a T2T strategy supported by a CDSS (T2T-CDSS) or a routine outpatient care (ROC) group. The CDSS provided evidence-based treatment recommendations based on disease activity measures. Feasibility outcomes included recruitment and retention rates. Usability was assessed with the System Usability Scale (SUS), completed by physicians in the T2T-CDSS group. Acceptability was evaluated using the Treatment Satisfaction Questionnaire (TSQ) and qualitative feedback. Exploratory outcomes included disease activity, remission rates and treatment modifications.

Results: Of 91 screened patients, 38 were enrolled (recruitment rate 42%) and 35 completed the study (retention rate 92%). The SUS score for the CDSS was 73.8, indicating good usability. Global satisfaction scores on the TSQ were stable over time and comparable between groups. Remission was achieved at least once by 61% (11/18) of patients in the T2T-CDSS group and 59% (10/17) in the ROC group. Both treatment intensifications and de-escalations occurred more frequently in the T2T-CDSS group compared with ROC (83% vs 47%). Treatment intensifications were observed in 61% of patients in the T2T-CDSS group vs 29% in the ROC group. Treatment de-escalation, represented by glucocorticoid tapering, occurred in 39% of T2T-CDSS patients compared with 18% in ROC. No statistically significant differences were observed between groups in disease activity outcomes or remission rates.

Conclusions: Implementation of a T2T strategy supported by a CDSS in SLE outpatient care was feasible, usable and acceptable to patients and physicians. Although qualitative feedback revealed important implementation barriers that should be addressed in future trials, the intervention facilitated proactive, target-driven treatment adjustments without compromising patient satisfaction and shows promise for implementing goal-directed therapy in SLE management.

Objective: The primary objective was to assess the prevalence of anti-ribosomal-P protein antibodies (anti-Rib-P) in a well-characterised Danish adult SLE cohort. Secondary objectives included (1) assessing any association between anti-Rib-P and neuropsychiatric SLE (NPSLE), (2) assessing any association between anti-Rib-P and characteristics of Danish patients with SLE and (3) assessing potential associations between selected autoantibodies and NPSLE.

Method: This cross-sectional study included 198 Danish patients with SLE from a population-based cohort. Patients meet the American College of Rheumatology's 1997 revised classification criteria for SLE and were 18 years of age or older. Anti-Rib-P were detected in serum using fluorescence enzyme immunoassay. ANA patterns were tested using indirect immunofluorescence on HEp-2 cells. Anti-double-stranded DNA antibody was examined by manual ELISA, and antibodies targeting Ro/SSA, La/SSB, Sm, RNP, Scl-70, Jo-1, Centromer B and Histone were examined on a Luminex instrument.

Results: We identified 14 (7.1%) patients with anti-Rib-P positive SLE, and 3 anti-Rib-P positive patients were diagnosed with NPSLE (21% of patients with NPSLE). There was no statistically significant association between anti-Rib-P and NPSLE. The mean anti-Rib-P titres in the patients with NPSLE did not differ significantly from patients without NPSLE patients' titres. We observed a significant association between anti-Rib-P positivity and disease activity measured by the SLEDAI-2K (SLE Disease Activity Index 2000) score. A stepwise logistic regression found an association between NPSLE and SLEDAI-2K and SLICC DI (SLE International Collaborating Clinics Damage Index) score.

Conclusion: This study could not confirm a role for anti-Rib-P in the identification of NPSLE. On the other hand, anti-Rib-P was associated with SLE disease activity as well as organ damage.

Objective: Using data from participants with paediatric SLE (pSLE) in the Childhood Arthritis and Rheumatology Research Alliance Registry, we aimed to: (1) describe 2-year disease activity trajectories, measured by the SLE Disease Activity Index 2000 (SLEDAI 2K); (2) identify characteristics associated with each trajectory and (3) assess achievement of lupus low disease activity state (LLDAS) and associated baseline characteristics.

Methods: Participants were diagnosed with pSLE within 12 months of baseline visit. Baseline sociodemographic, clinical and treatment characteristics were included in latent trajectory analyses. Associations between patient characteristics with trajectory groups and LLDAS were analysed with multinomial generalised logistic regression modelling.

Results: 1002 patients were screened; 553 were included for SLEDAI 2K and 269 for LLDAS analyses. SLEDAI 2K trajectories included (T1) low and stable, (T2) high and decreasing, (T3) intermediate and stable. In multinomial generalised logistic regression, baseline SLEDAI 2K score and insurance type were significantly associated with trajectories. 51% (136/269) of patients achieved LLDAS at least once in 24 months as compared with 17% (47/269) at first assessment. LLDAS attainment at both time points was predicted by lower pain interference scores; LLDAS attainment over 24 months was also associated with baseline American College of Rheumatology classification criteria, rituximab use at baseline and highest completed level of parent/guardian education.

Conclusions: Disease activity trajectories in a pSLE cohort were predicted by baseline SLEDAI 2K and insurance. Only half of the patients achieved LLDAS during the 2-year study period, which was predicted by baseline characteristics including pain interference. The relationship between disease activity and socioeconomic factors and pain warrants further investigation to identify modifiable factors to reduce pSLE disease activity.

Objective: SLE is a multisystem autoimmune disease characterised by chronic inflammation and progressive organ damage, including ovarian dysfunction. This study investigated the therapeutic efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in ameliorating ovarian impairment and restoring ovarian function through the inhibition of fibrosis in a lupus mouse model.

Methods: Serum levels of sex hormones were quantified via ELISA. Ovarian tissue samples were histologically evaluated for follicle count and fibrosis via H&E and Masson's trichrome staining. Quantitative reverse-transcriptase-PCR, western blot, immunofluorescence and immunohistochemistry were employed to evaluate inflammatory cytokines, fibrotic factors, hormone receptors and signalling proteins. Primary granulosa cells (GCs) isolated from lupus mice (MRL/lpr) were cocultured with MSCs and the expression of fibrotic factors was analysed by western blot. Additionally, a human GC line (KGN) was used to further explore the relationships among connective tissue growth factor (CTGF), focal adhesion kinase (FAK)/FAK-Tyr576/577 phosphorylation and fibrosis. This was achieved through stimulation with recombinant CTGF, the CTGF antagonist FG-3019 or the FAK inhibitor SU6656.

Results: UC-MSC transplantation significantly downregulated the expression of proinflammatory cytokines (Tnf-α, Il-1β) and fibrotic markers (Ctgf, α-Sma) while upregulating the expression of key hormone receptors (Amh, Esr1, Esr2). Additionally, a reduction in CD3⁺/CD4⁺ T-cell infiltration, C3 complement deposition and IgG levels was observed, accompanied by an increase in regulatory T cells. Further analysis revealed that fibrotic markers and FAK-Tyr576/577 phosphorylation were markedly suppressed in primary ovarian GCs following MSC transplantation. In vitro experiments demonstrated that recombinant CTGF promoted fibrogenesis in the human GC line KGN. Conversely, MSC treatment inhibited phosphorylated FAK-Tyr576/577 and downregulated the expression of Collagen 1 and α-SMA, suggesting that UC-MSCs alleviate ovarian fibrosis by suppressing FAK-Tyr576/577 phosphorylation.

Conclusion: This study demonstrated that UC-MSC treatment ameliorated ovarian dysfunction and attenuated ovarian fibrosis in lupus mice by modulating the CTGF/FAK-Tyr576/577 phosphorylation pathway.

Background: Endotoxaemia without infection in lupus is mentioned with the inconclusive clinical importance.

Methods: With endotoxaemia and lupus activity (Systemic Lupus Erythematosus Disease Activity Index 2000 score), 46 patients with childhood-onset lupus were categorised into active lupus with endotoxaemia (n=14), inactive lupus with endotoxaemia (n=10), active lupus without endotoxaemia (n=10) and inactive lupus without endotoxaemia (n=12). The routine parameters (serum creatinine, urine sediments, proteinuria, complement, haematological aspects and histological activity index) were analysed with lupus activity and other parameters.

Results: Serum cytokines (tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and IL-10), serum citrullinated histone H3, cell-free DNA and bacterial-free DNA were not different among groups. The extracellular traps (ETs) in the peripheral blood mononuclear cell (PBMC) fraction, measured by immunofluorescence of myeloperoxidase (MPO) and neutrophil elastase (NE), were elevated in endotoxaemia regardless of lupus disease activity. Interestingly, low-density granulocytes (LDGs), the neutrophils in the PBMC fraction after gradient separation, were elevated in active lupus regardless of endotoxaemia but higher in the patients with positive endotoxaemia. Because endotoxaemia might be derived from the gut, the blood microbiome was measured, and the Burkholderia group was the representative bacteria in active lupus with endotoxaemia. The incubation of LPS or bacterial-free DNA with neutrophils from the healthy control altered these regular-density neutrophils to LDGs.

Conclusion: Endotoxaemia presented in both active and inactive lupus (possibly correlated with some bacterial groups in the gut) that caused ETs in the PBMC fraction and LDGs. However, elevated LDGs were most prominent in endotoxaemia with active lupus.

Objective: To identify factors associated with individual Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) accrual items in 1385 patients from the Latin American SLE incident cohort (GLADEL (Grupo Latino Americano Del Estudio de Lupus)).

Methods: Longitudinal cohort study. SDI assessed yearly, and damage accrual defined as a SDI change in any individual item during follow-up. Sociodemographic and clinical characteristics at entry, along with regular medication use up to the month prior to each damage item accrued, were analysed using multivariate Cox proportional hazard models with time-varying hazard risk effect performed. Models for overall damage and 10 items with at least 28 patients per item are reported.

Results: New damage was accrued by 658 patients with SLE (48%) over a median of 54 months (p25-75: 29-71) of follow-up. Mestizo ethnicity, recent SLE Disease Activity Index (SLEDAI) and immunosuppressants were predictors of overall damage accrual, while antimalarials and rural residence were protectors; mixed effects were observed for SDI >0 and glucocorticoids (GCs) use. Protectors for scarring chronic alopecia (23.7% at 7 years follow-up) included older age, longer disease duration, diagnostic delay, SDI >0 and cytotoxic use. Proteinuria >3.5 g/24 hours (11.5% at 7 years follow-up) was associated with protective factors like older age, longer disease duration and higher GCs dose, while risk factors were Mestizo ethnicity, low medical coverage, higher SLEDAI scores and cytotoxic use. In addition, Mestizo ethnicity was a risk factor for estimated glomerular filtration rate <50% and end-stage renal disease (ESRD) whereas antimalarial protected from ESRD. GCs were risk factors for pericarditis, retinal change or optic atrophy but provided protection against proteinuria >3.5 g/24 hours. Recent disease activity and cytotoxic use were significant risk factors for additional items.

Conclusions: Factors associated with damage accrual differ substantially by individual SDI items. Mestizo ethnicity and recent disease activity increased renal risks, while antimalarials were protective. GCs showed mixed effects. Item-specific strategies are crucial to mitigate long-term damage.

Objective: The association of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and SLE was previously described, but patients with iTTP with coexistent SLE remain poorly characterised.

Methods: We compared the clinical presentation and the outcome of patients with iTTP with coexistent SLE (SLE-iTTP) to an age-sex matched cohort of patients with idiopathic iTTP without SLE.

Results: During the study period, 1409 patients with iTTP were recruited in our registry. Of these, 79 (6%) had a prior or concurrent diagnosis of SLE at the time of iTTP diagnosis, and 437 (31%) had detectable ANAs without other clinical features of SLE. When compared with idiopathic iTTP, patients with SLE-iTTP had more severe renal involvement, and cardiac involvement was more prevalent, whereas central nervous system involvement was less common. Patients with SLE-iTTP received more immunosuppressive agents. There was no difference in response categories during the acute phase. During follow-up, SLE-iTTP had superior ADAMTS13 relapse-free survival than idiopathic iTTP. Among patients with ANAs without other clinical features of SLE, 33 (8%) were diagnosed with SLE 27 months (IQR: 7-65 months) following iTTP diagnosis; 32 additional patients (7%) developed another systemic autoimmune disease. No patient from the idiopathic iTTP group developed clinical SLE during follow-up.

Conclusion: Patients with iTTP are prone to develop autoimmune features, and patients with SLE-iTTP have distinct clinical features and outcome. Relapse-free survival seems better in patients with SLE-iTTP, underscoring the need for tailored management strategies in this population, including a specific follow-up to assess early features suggestive of SLE.

Trial registration number: NCT00426686.

Objective: Our primary objective was to estimate an updated prevalence of SLE in France in 2020. We also explore the sociodemographic characteristics of patients with SLE, the social and spatial variability and also study and use hydroxychloroquine prescription patterns as an external validation for case ascertainment.

Methods: We used the French national health data system, which covers almost all of the 67 million people living in France. Prevalent cases were identified among inpatients and people granted a long-term disease status, using the International Classification of Diseases, 10th Revision code for SLE. Filled prescriptions of hydroxychloroquine were also counted.

Results: In 2020, we identified 54 804 patients with SLE; this corresponds to an overall prevalence of 81.6 per 100 000 people. The prevalence estimates were 137.0 per 100 000 in women and 22.5 per 100 000 in men. The highest standardised prevalences were observed in the French overseas departments and in the mainland departments to which people from these departments frequently migrate. Unexpectedly, we did not find an association between the prevalence of SLE in mainland France and a social deprivation index. A prescription of hydroxychloroquine was filled at least once for 67.7% of the patients overall and reached 86.7% of those aged between 20 and 24.

Conclusions: Our study provides recent, accurate estimates of the prevalence and social and geographical distribution of SLE in France. We observed an almost twofold increase in prevalence, relative to a previous estimate (from 2010) based on the same database. The high proportion of patients receiving a prescription of hydroxychloroquine is in line with current treatment guidelines.