Lupus最新文献

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.

BackgroundOver-activated Type I interferon (IFN-I) signaling has been widely documented in systemic lupus erythematosus (SLE), but the underlying mechanisms and role of IFN-inducible long noncoding RNAs (lncRNAs) are still being explored. Our study highlights LINC01410 as a novel IFN-α-inducible lncRNA with potential contributions to SLE and LN.Materials and methodsHuman peripheral blood mononuclear cells (PBMCs) were collected from SLE patients and healthy donors. THP-1, HEK293 T, Jurkat T, and Raji B cell lines were treated with 1000 U/mL IFN-α to evaluate changes in LINC01410 expression. LINC01410 was further overexpressed in THP-1 cells to assess effects on cell proliferation, apoptosis, and macrophage polarization, coupled with measurements of cytokines IL-6 and TNF-α. Additionally, Western blot assays were performed to elucidate LINC01410-associated pathways and protein changes.ResultsLINC01410 was found to be significantly upregulated in SLE PBMCs compared to healthy controls, and its expression was further elevated by IFN-α stimulation in multiple immune cell lines and primary immune cells. Overexpression of LINC01410 in THP-1 cells promoted proliferation, inhibited apoptosis, and drove macrophage differentiation toward an M1 phenotype, with an increase in proinflammatory cytokines such as IL-6 and TNF-α. Enrichment analyses linked LINC01410 to several dysregulated immune processes, consistent with SLE's immunopathology. Cross-dataset validation revealed that LINC01410 modulates key miRNAs, including miR-34a-5p, miR-125a-3p, and miR-185-5p, via the competing endogenous RNA (ceRNA) mechanism, thereby exerting pivotal regulatory effects on critical pathways such as cell cycle regulation, adherens junction, and the PI3K-Akt signaling pathway.ConclusionsOur findings reveal that LINC01410 is an IFN-I-responsive lncRNA that contributes to hyperactive immunity in SLE by modulating monocyte-macrophage function. LINC01410 may represent a novel biomarker and therapeutic target for overcoming disease flares and tissue damage associated with SLE.