Lupus最新文献

BackgroundNeonatal lupus erythematosus (NLE) is a potentially life-threatening condition resulting from the transfer of autoantibodies from the mother to the fetus, with congenital heart block (CHB) its most serious complication. Despite the potential severity, therapeutic strategies remain limited. The objective was to systematically evaluate all registered clinical trials to date for the treatment or prevention of NLE and its cardiac manifestations.MethodsWe searched the Clinicaltrials.gov database on January 24, 2025, to identify all registered clinical trials for NLE treatments since 1994. This online registration of clinical trials is maintained by the NLM, a division of the National Institutes of Health (NIH), and mandates regular trial updates and timely results reporting. The registry provides specifics on a clinical trial, such as a national clinical trial (NCT) number, current recruitment status, study type, and other important data related to the trial. Principal investigators must submit results within 1 year of the trial's primary completion date.ResultsThree eligible trials for NLE were found on the NLM clinical trials database. One trial reported that hydroxychloroquine treatment reduced the recurrence rate of congenital heart block by more than half, from 18% to 7.4%. The remaining studies explored intravenous immunoglobulin and dexamethasone without posting results.ConclusionCongenital heart block from NLE was decreased in recurrence by treatment with hydroxychloroquine. However, the scarcity of research towards advancing care for these conditions highlights a major gap in this area.

BackgroundCutaneous lupus erythematosus (CLE) is a complex autoimmune condition with limited data on its molecular underpinnings. Saliva, as plasma filtrate fluid may be a promising tool for biomarkers discovery, given its easy accessibility.ObjectiveThis study aimed to characterize the salivary proteomic profile of CLE patients compared to healthy controls to identify potential disease-specific biomarkers.MethodsTen females diagnosed with CLE and eleven controls without autoimmune conditions were included in the study. Saliva samples were collected under controlled conditions and analysed using mass spectrometry and chromatography, performed with the nanoElute nanoflow system coupled to a timsTof-Pro mass spectrometer.ResultsAmong the 104 proteins identified, six showed statistically significant differences between groups. PEBP1 (RKIP), ARG1, TALDO, and CTSZ were upregulated in CLE, while TFF3 and PRDX4 were absent. PEBP1 and ARG1 showed high discriminatory power (AUROC = 1.0), suggesting their potential as CLE biomarkers. Data are available via ProteomeXchange with identifier PXD064580.ConclusionThis study establishes a distinct salivary proteomic signature in CLE, highlighting proteins with diagnostic potential. Saliva proteomics offers a powerful approach to unravel CLE pathophysiology supporting future research on non-invasive biomarkers for disease monitoring and personalized care.

PurposeThe Giscombé Superwoman Schema Questionnaire (G-SWS-Q) consists of five sub-domains. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that disproportionately impacts Black women and for which psychosocial mechanisms are of high relevance to well-being. The main objective of this study is to validate the G-SWS-Q factor structure among a sample of Black women living with SLE using confirmatory factor analysis (CFA).MethodsParticipants are part of Georgians Organized Against Lupus, a population-based SLE cohort in Atlanta. We measured SWS using the G-SWS-Q containing 35 items across five subdomains. We restricted to those identifying as Black women (n = 584). CFA was performed and model fit was assessed using standard fit indices and procedures for model re-specification in Mplus 8.1.ResultsThe mean age of respondents was 48 years (SD: 13.3)) and number of years of living with SLE was 16 (Median: 14.6, IQR: 7.9-21.22). All items were retained in the scale. After modifying the model by adding within latent factor error covariances, we obtained satisfactory model fit (RMSEA = 0.052; CFI = 0.90; SRMR = 0.063), which suggested that the factor structure is valid in this sample of Black women with SLE.ConclusionsOur findings confirm the factor structure suggested by G-SWS-Q for Black women living with SLE. The SWS has the potential to better understanding of psychosocial mechanisms underlying adverse health outcomes experienced by Black women by centering a gender- and race-specific orientation, with implications for engagement with health behaviors and disease management. In SLE, framing studies connecting chronic symptoms and their connection to quality of life with SWS may elucidate these mechanisms.

Objectives(I) to study the association between antiphospholipid antibodies (aPL) and severe preeclampsia (PE) and (II) To assess the correlation between aPL and severe PE before and after 34 weeks of gestation.Study DesignThis prospective and interventional study included one hundred forty pregnant women separated in two groups based on their diagnostic status of PE.Control GroupForty normal pregnant women beyond 20 weeks of pregnancy. Tested for aPL: during they obstetric control and followed until birth. We only included volunteers who completed pregnancy without pathologies and with a normal full-term new-born baby.Study group (SG)One hundred women with diagnosis of severe PE. Tested for aPL: at time of severe PE onset and followed until birth. We stratified SG according to weeks of gestation at the time of diagnosis of severe PE (early and late PE), cut-off point of 34 weeks.We compare the frequency of aPL positivity between control versus SG.We've preformed two comparisons.a) Healthy Controls and patients with severe preeclampsia.b) In the study group comparison of early severe preeclampsia and late severe preeclampsia.ResultsWe compared the presence of aPL between Control 10.0% (4/40) and SG 34.0% (34/100). We found an association between severe PE and aPL positivity [OR = 4.63 (95% CI: 1.523 - 14.107), p = .005].We confirmed an association between early severe PE and the presence of aPL positivity [OR = 4384 (95% CI: 1.3615 - 14.1206), p = .01]. We also found an association between late severe PE and the presence of aPL positivity [OR = 5.0 (95% CI: 1.4901 - 16.777), p = .008].ConclusionThese results suggest that the presence of aPL is associated to severe PE. The positivity of aPL is associated to severity of PE, independently from gestational age.

BackgroundSuboptimal medication adherence in systemic lupus erythematosus (SLE) significantly contributes to poor patient outcomes. However, a comprehensive synthesis of global evidence remains limited.ObjectiveTo systematically synthesize global evidence on factors influencing medication adherence in patients with SLE, categorize these determinants according to the World Health Organization's multidimensional framework, and develop a conceptual model of adherence.MethodsWe conducted a systematic review of studies published between 2000 and 2020 in PubMed, Scopus, and Web of Science, following PRISMA 2020 guidelines. Eligible studies included observational or qualitative research that examined factors related to adherence in patients with SLE. Of 362 records screened, 24 studies were included (N = 200,807). Because of heterogeneity in study design, populations, adherence measures, and reported effect sizes, a meta-analysis was not feasible. A narrative synthesis was performed, and effect measures were reported as presented in the original studies.ResultsStructural disadvantages emerged as major barriers to adherence. Patients with very low or low socioeconomic status (OR = 2.6, 95% CI: 1.6-4.3) and those living in rural areas (OR = 3.4, 95% CI: 1.4-5.0) were more likely to be non-adherent. Racial residential segregation was also associated with reduced access to healthcare resources and lower adherence rates (OR = 0.80, 95% CI: 0.67-0.96). These disadvantages were linked to impaired provider-patient communication (β = -0.41, p < .001), which in turn weakened trust in treatment (γ = 0.68). Trust in treatment functioned as a critical mediator of adherence (R² = 0.83). Clinically, poor adherence was associated with increased disease activity (HR = 2.11, 95% CI: 1.75-3.02) and greater psychological burden (OR = 5.7, 95% CI: 3.8-7.9). Cognitive decline also contributed, with each one-point decrease in MMSE scores linked to a 7.2% increase in missed doses.ConclusionMedication adherence in patients with SLE reflects the combined influence of structural inequalities and modifiable mediators. Socioeconomic disadvantage and segregation require systemic interventions, whereas provider-patient communication, treatment trust, and psychological support represent more immediate targets for action. Multilevel strategies are needed to address disparities and improve outcomes in SLE care.

ObjectiveWhile oral glucocorticoids (GC) have improved the prognosis of lupus nephritis (LN), dose reduction to ≤5.0 mg/day is recommended, considering their toxicity. We investigated the real-world prescription status following dose reduction of oral GC after starting initial therapy in patients with LN.MethodsData were extracted from the JMDC insurance claims database between May 2016 and March 2023 with the following inclusion criteria: patients with ≥2 LN diagnoses; follow-up for ≥90 days pre-index and ≥540 days post-index; oral GC dose ≥20.0 mg/day (prednisolone equivalent) or intravenous glucocorticoid pulse; ≥2 urinalyses, anti-double stranded DNA antibody, and complement tests within 360 days post-index. Descriptive analyses were performed by characterization as dose reduction target (GC ≤5.0 mg/day at Day 540) 'achieved' or 'non-achieved' groups.ResultsMean oral GC baseline dose for the overall population (n = 295) was 36.1 mg/day. The two most prescribed immunosuppressants were mycophenolate mofetil (MMF; 41.7%) and tacrolimus (TAC; 16.9%). The proportion of patients with prescribed GC doses ≤5.0 mg/day was 1.0% on Day 1 and 48.1% on Day 540. In the achieved and non-achieved groups, the baseline concomitant immunosuppressants were MMF: 51.4% and 32.7% and TAC: 15.5% and 18.3%, respectively, while the proportion of patients with GC ≤7.5 mg/day was 31.0% and 12.4% on Day 180, respectively.ConclusionThese real-world administrative data show the actual oral GC prescription status after starting initial LN therapy in Japan. Approximately half of the patients with LN were prescribed GC ≤5.0 mg/day within 1.5 years after starting the initial therapy.

AimsLupus nephritis (LN) is common in systemic lupus erythematosus (SLE) and is associated with adverse renal outcomes and premature mortality. There is limited data examining LN outcomes in Aotearoa New Zealand and none examining outcomes since mycophenolate mofetil (MMF) became subsidised for use in class III/IV LN induction. We describe a cohort of adults with biopsy-confirmed LN over an 18-year period in two regions of Aotearoa New Zealand, including LN characteristics, treatment, and outcomes.MethodsCases were identified from laboratory databases and relevant data extracted from patient records. Response was defined per Kidney Disease, Improving Global Outcomes (KDIGO) with overall renal response (ORR) defined as at least partial response (PR). Outcomes among patients with class III/IV LN were explored by induction treatment and timing of MMF restrictions.ResultsOne hundred cases were identified, including 74 with class III/IV LN. Most (85/100) were women, living in urban areas (78%), with ethnicities including Māori (25%), Pacific (13%) and NZ European (38%). The median age at LN diagnosis was 38 years (range 18-74) and the median time between SLE diagnosis and renal biopsy was 2 years. In the MMF-restricted period, MMF was used for induction in class III/IV LN in 43% (12/28) of cases, and in 72% (33/46) of cases in the MMF-unrestricted period (p = .01). In the MMF-unrestricted period, use of high dose cyclophosphamide stopped (18% to 0%), complete response (CR) rates doubled (14% to 33%, p = .08) whereas rates of ORR did not show statistically significant change (39% to 50%, p = .37). At last-observed follow up (mean 7 years from biopsy) 26/74 (36% cases) had poor outcomes with no renal response.ConclusionIn this LN cohort in Aotearoa New Zealand, half of people with LN class III/IV do not achieve early renal response and over one-third have poor outcomes over less than a decade of follow up. Subsidy of MMF substantively increased its use and patients in this time period had better rates of good LN outcomes. These data suggest considerable unmet need for effective treatments for LN and that funding of effective medicine for LN increases their use and improves LN outcomes.

Background/PurposeThe B cell Activating Factor (BAFF) signaling pathway influences rheumatic disease through its role in the selection, maturation, and survival of B cells. Increased BAFF also correlates with hypertension and preeclampsia in pregnant women without rheumatic disease. We sought to correlate BAFF levels in pregnancy with pregnancy outcomes among women with rheumatic disease.MethodsBlood samples, disease activity assessments, labs, and pregnancy outcomes were prospectively collected from pregnant women with systemic lupus erythematosus (SLE). Inclusion criteria were enrollment prior to 30 weeks gestation and known pregnancy outcome. Preeclampsia diagnosis was determined through chart review and consensus among 6 providers (maternal-fetal medicine, nephrology, and rheumatology); pregnancies were excluded if a preeclampsia diagnosis could not be agreed upon. We assessed for changes in BAFF levels throughout pregnancy, and we investigated its association with disease activity and adverse pregnancy outcomes.ResultsThis study included 408 samples in 230 women with SLE (n = 110) and other rheumatic diseases (n = 120). The average maternal age was 31.3 years and self-reported race was 5% Asian, 30% Black, and 61% White. The median level of BAFF was significantly higher in the 1st trimester compared to the 2nd and 3rd trimester measures (p = .002). Among women with SLE, compared to pregnancies without preeclampsia, those with preeclampsia had significantly higher BAFF levels in the first trimester (2061 vs 1217 pg/mL, p = .007). In models adjusted for age, obesity, and maternal race, patients with SLE experienced a 19% higher odds of developing preeclampsia with every 100-unit increase BAFF in the first trimester (AOR 1.19; 95% CI: 1.05, 1.36). Women with SLE and elevated BAFF levels were more likely to have elevated dsDNA, but not more likely to experience lupus nephritis during pregnancy.ConclusionThis study found elevated BAFF levels in the first trimester of pregnancy were associated with subsequent development of preeclampsia. While elevated BAFF was associated with elevated dsDNA, it was not associated with lupus nephritis, the strongest predictor of preeclampsia among women with SLE. This finding suggests that elevated BAFF early in pregnancy may be a novel risk factor for poor pregnancy outcomes in women with SLE.

PurposeModifying iron metabolism to mitigate oxidative stress and rebalance the Th17/Treg cell ratio in systemic lupus erythematosus (SLE) may represent a promising therapeutic target for treating SLE.MethodologyWe used the iron chelator deferoxamine mesylate (DFO) and a low iron diet (LID) to treat imiquimod (IMQ)-induced lupus-like syndrome in mice. We observed the changes in T lymphocytes and iron metabolism in the spleen. Splenic naive CD4⁺T cells were induced to differentiate into Th17 and Treg cells through magnetic separation and were cultured with DFO solution to observe the effect of DFO on the balance of Th17/Treg cells. Ras-selective lethal3 (RSL3)-induced ferroptosis in Naïve CD4⁺T cells was treated with DFO.Major FindingsWe found that iron deficiency may promote the expansion of Treg cells and suppress the production of Th17 cells by activating the Nrf2/HO-1/GPX4 signaling pathway, reducing the accumulation of reactive oxygen species (ROS), and thus halting the progression of IMQ-induced lupus-like disease.ConclusionIron deficiency, both in vitro and in vivo, inhibited the inflammatory response, reducing the production of inflammatory cytokines. This could present a possible therapeutic approach for SLE.