Lupus Science & Medicine最新文献

Background: The purpose of this study was to reveal the morphological changes of grey matter (GM) in women systemic lupus erythematosus (wSLE) patients with mild cognitive impairment (MCI) with normal conventional MRI.

Methods: The differences in brain morphological indicators among wSLE with MCI, wSLE without MCI and women healthy control (wHC) group were calculated and compared by voxel-based morphometry and surface-based morphometry. The GM volume (GMV), cortical thickness (CT), indicators of cortical complexity, including fractal dimension (FD), gyration index (GI), sulcus depth, the relationship between brain morphological indicators and clinical features, were analysed.

Results: In comparison to wSLE patients without MCI (n=36), wSLE with MCI (n=26) demonstrated a significant decrease in FD of the left lateral orbitofrontal gyrus. When compared with the wHC group (n=36), both wSLE patients with MCI and wSLE without MCI group exhibited a reduction in GMV in the medial of right superior frontal gyrus, a thinning of CT in the left paracentral and postcentral gyrus as well as in the right pars triangularis gyrus and superior frontal gyrus. Within the wSLE group, Mini-Mental State Examination scores were positively correlated with GMV in the middle of right superior frontal gyrus and with the FD of the left lateral orbitofrontal gyrus.

Conclusion: WSLE patients with MCI have brain morphological changes such as reduced GMV, thinning CT, reduced FD and increased GI. Cortical morphological changes may be involved in the pathological process of MCI in wSLE patients.

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by multiorgan involvement. Osteoporosis and fragility fractures, particularly vertebral fractures, are significant, yet often underestimated, comorbidities in patients with SLE. This study aims to evaluate the prevalence of vertebral fractures and their associations with demographic, disease-related and therapy-related factors in patients with SLE.

Methods: We conducted a monocentric, cross-sectional study to systematically evaluate bone health using dual-energy X-ray absorptiometry and vertebral fracture assessment (VFA). Associations between vertebral fractures and clinical, laboratory variables were investigated with logistic and linear regressions.

Results: One hundred and six patients with SLE were included. The overall prevalence of radiographic vertebral fractures was 21.7%, whereas clinical vertebral fractures were reported in 14.2% of patients. New, previously not diagnosed, radiographic vertebral fractures were detected in 14.2% of all patients with SLE at screening with VFA. Older age, longer disease duration, cumulative glucocorticoid (GC) dose and lower bone mineral density were significantly associated with vertebral fractures. Cumulative GC dose had the strongest association with vertebral fractures. We also found a positive association between the number of vertebral fractures on VFA and cumulative GC dose (β 0.025, p=0.025).

Conclusions: Our findings underscore the importance of actively screening for vertebral fractures in patients with SLE, especially those on long-term GC therapy, to prevent underdiagnosis, mitigate the risk of further skeletal damage and facilitate the timely initiation of targeted antiosteoporotic treatments when indicated.

Trial registration number: NCT05590390.

Background: SLE has increased risk of invasive pneumococcal disease due to immune dysregulation and immunosuppression. European Alliance of Associations for Rheumatology recommendations suggest sequential vaccination with conjugate vaccine, followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23). However, data on immunogenicity of sequential vaccination in SLE are limited.

Methods: Adult patients with SLE (American College of Rheumatology 2019 criteria) with inactive disease, stable immunosuppression for 3 months and prednisolone ≤10 mg/day were included. Sequential arm received 10-valent pneumococcal conjugate vaccine, followed by PPSV23. The second arm received only PPSV23. The two cohorts were recruited independently without randomisation. Antibodies at baseline and 12-14 weeks to pneumococci (serotypes 1, 5, 6B, 14 and 19F) were measured by ELISA and opsonophagocytic assay for functional antibodies. The primary outcome was a twofold increase in 3/5 serotypes. 40 subjects were enrolled in each arm and 15 healthy adults for response to PPSV23.

Results: 35 completed the study in the PPSV23 arm and 34 in the sequential arm. Baseline parameters were comparable.Response to PPSV23 was poorer in SLE (74.28%) compared with healthy controls (100%). There was no difference in the primary outcome between sequential vaccination (82.35%, 95% CI 68% to 94%) and PPSV23 (74.28%, 95% CI 60% to 89%). All 15 non-responders were on prednisolone. Among responders, only 41/54 (76%) were on prednisolone. There was no difference in other immunosuppressive drugs. Increasing age predicted poor response on multivariable analysis in all serotypes.Major adverse events included one event of Miller Fisher variant of Guillain-Barré syndrome in the sequential arm. Minor adverse events included one each with injection-site pain, migraine, fever and fatigue after conjugate vaccine, and one with fever after PPSV23. Three minor adverse events in the PPSV23 group included one each with injection-site pain, herpes zoster, headache and fever. In the PPSV23 arm, three minor flares were seen, while in the sequential arm, one major flare and one minor flare occurred.

Interpretation: Both vaccination strategies are safe with adequate antibody response. In low- and middle-income countries, a single-dose PPSV23 may be adequate if cost negates sequential vaccination.

Background: SLE is an autoimmune disease that varies across ethnic populations and the regions that cause economic burdens, but nationwide epidemiological data for Thailand are lacking.

Objective: To estimate the incidence and prevalence of SLE in Thailand between 2017 and 2020.

Methods: A retrospective cohort study used the Information and Communication Technology Center, Ministry of Public Health, covering all major healthcare insurance systems (nearly 90% of hospitals, about 80% of the Thai population). Adults (≥18 years) with a primary diagnosis of SLE (International Classification of Diseases 10th Revision code M32) were included. Point and period prevalence (per 100 000 population) and annual incidence rates (per 100 000 person-years) were calculated overall and stratified by year, age, sex and region, with 95% CIs.

Results: In 2017, 55 956 prevalent cases were identified among 65 204 797 of the total Thai population, yielding a point prevalence of 85.8/100 000 (95 % CI 85.1 to 86.5). Prevalence was highest in women (152.9 vs 15.9/100 000; female-to-male ratio 9.6:1), in the 40-49 year age group (128.3/100 000) and in the southern region (178.5/100 000). From 2018 to 2020, incident SLE cases numbered 15 403, 16 243 and 15 925, corresponding to annual incidence rates of 23.6, 24.8 and 24.3/100 000 person-years, and the cumulative incidence for the 3 years was 72.7/100 000 person-years (95 % CI 72.0 to 73.4). Incidence peaked at ages 40-49 in 2019 (33.7/100 000) and was consistently highest in the south (60.0, 53.9 and 57.3/100 000 person-years in 2018-2020).

Conclusions: SLE is relatively common in Thailand, particularly among women of reproductive age and residents of the southern region. These nationwide data support SLE service planning in Thailand and may guide resource allocation in other Southeast Asian health systems expanding universal coverage.

Objective: This study aimed to leverage machine learning algorithms to explore the relationship between anti-double-stranded DNA (anti-dsDNA) immunoglobulin G (IgG) glycosylation and the degree of organ involvement in patients with SLE.

Methods and analysis: We enrolled 86 consecutive treatment-naïve patients with SLE positive for anti-dsDNA antibodies from the Department of Rheumatology and Immunology at Ruijin Hospital, Shanghai, between 2017 and 2019. We quantified and classified the degree of organ involvement in patients with SLE and analysed each glycoform and a combination of glycoforms of purified anti-dsDNA IgG. A random forest classifier and artificial neural network were applied to evaluate the correlation between the levels of glycoform pairs and the degree of organ involvement.

Results: Pearson's correlation analysis revealed a strong connection between the involved and uninvolved organs in patients with SLE. Random forest analysis showed that the combination of IgG1Gal and IgG3/4Bis had the highest accuracy (0.7692) and area under the curve (0.8187). In terms of predicting the degree of involvement using an artificial neural network, IgG3/4Bis and IgG1Gal showed the lowest mean squared error (0.0244).

Conclusions: Our study showed the effectiveness of combining glycoforms to classify and predict the degree of SLE organ involvement. Different glycoforms were correlated with the involvement degree to various extents, and the combination of anti-dsDNA IgG3/4Bis and IgG1Gal exhibited the best correlation with organ involvement.

Objective: To investigate the two-dimensional speckle-tracking echocardiography (2D-STE) parameters associated with early impaired left ventricular systolic function in SLE patients and to estimate the potential clinical factors that may trigger and influence left ventricular systolic dysfunction.

Methods: This study collected a total of 36 patients admitted to the rheumatology and immunology department of Sun Yat-sen University between January 2020 and December 2021, who were newly diagnosed with SLE and had a Systemic Lupus Erythematosus Disease Activity Index 2000 Score≥4 points. An equal number of healthy controls matched for gender and age were included. All participants underwent routine echocardiography and two-dimensional speckle-tracking echocardiography (2D-STE) examinations. Various clinical data were also collected. Machine learning and regressions were used to estimate potential risk factors for left ventricular systolic dysfunction in SLE patients.

Results: Significant differences in 2D-STE parameters were found, including global longitudinal peak systolic strain (GLPS) (p-adjust<0.001), GLPS strain obtained from the apical two-chamber view and GLPS strain obtained from the apical four-chamber view (GLPS-A4C) (p-adjust=0.005), and GLPS strain obtained from the apical long-axis view (GLPS-APLAX) (p-adjust=0.003) between SLE patients and controls. Machine learning models, particularly GLPS-APLAX, showed excellent discrimination ability with an AUC of 0.93 (95% CI: 0.89 to 0.96) and an area under the precision-recall curve of 0.96. Multivariate regression further highlighted the inverse relationship between anti-U1 small nuclear ribonucleoprotein (U1RNP) antibodies and four GLPS-related continuous variable measures, with GLPS, GLPS-A4C and GLPS-APLAX measures having statistically significant effects (eg, GLPS coefficient=-3.71, 95% CI: -5.91 to -1.51, p=0.002).

Conclusions: This case-control study revealed that 2D-STE parameters can be used to predict subclinical cardiac dysfunction in SLE patients, and anti-U1RNP antibodies may be an essential predictive clinical factor. Machine learning may further assist in preliminary screening and quantifying left ventricular systolic dysfunction reasons in SLE patients.

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.