Lupus最新文献

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.

ObjectivePatients with systemic lupus erythematosus (SLE) often have concomitant fibromyalgia (FM) or similar symptoms including chronic pain, fatigue, or depression. This study explored whether Patient-Reported Outcomes Measurement Information System (PROMIS) measures provide richer information than 2016 American College of Rheumatology (ACR) FM criteria survey.MethodsPatients with SLE in our convenience cohort were categorized into groups: (1) concurrent FM chronic pain, (2) concurrent non-FM chronic pain, and (3) no chronic pain using 2016 ACR FM Survey. Based on PROs in the FM Survey, we captured comparable PROMIS measures (e.g., depression, fatigue). Associations by pain group were tested using Kruskal-Wallis rank sum test, Shapiro-Wilk normality test, chi-squared test, or Fisher's exact test. Violin plots explored differences across groups.ResultsThe cohort (n = 181) included 31 patients with FM pain, 23 with non-FM chronic pain, and 127 with no chronic pain. Median PROMIS symptom scores (fatigue, sleep disturbance, pain intensity and interference, depression) were highest and cognitive function lowest in the FM group, despite 13% being in remission. There were significant differences on 4 PROMIS measures (cognitive function, fatigue, pain intensity, pain interference) between FM pain and non-FM pain groups (p < .02), the former being worse. There were no significant differences in SLE Disease Activity Index (SLEDAI) score.ConclusionSLE patients with non-FM chronic pain have similar symptoms to FM compared with SLE patients without chronic pain; however, symptoms are not as severe as those meeting FM criteria. PROMIS measures may be used to classify severity more precisely for disease categorization and management.

IntroductionWhile Systemic Lupus Erythematosus (SLE) typically presents with a multifactorial etiology, rare monogenic forms exist, usually diagnosed during childhood with a severe clinical course. This study aims to identify monogenic causes of SLE within the pediatric population of Northern Israel and to suggest criteria for genetic evaluation in patients with childhood-onset SLE.MethodsClinical and genetic data were collected from a single tertiary pediatric medical center in Israel, between 2010 and 2021. Patients diagnosed with SLE before the age of 18 years were enrolled in the study. Monogenic SLE was suspected in patients with any of the following criteria: (1) family history of SLE, (2) consanguinity, (3) early onset of symptoms (under 10 years), (4), atypical clinical course, (5) male gender, (6) syndromic features. Genetic evaluations were performed for these patients.ResultsSeventy-five patients were diagnosed with SLE, of whom 18 (24%) met the criteria for suspected monogenic SLE. Genetic evaluations were conducted for 13 out of the 18 patients (72%) leading to a diagnosis of a monogenic form of SLE in 6 of the 13 patients (46%), and total of 8% from the entire cohort. Four patients were diagnosed with prolidase deficiency, one patient with Aicardi-Goutières syndrome (AGS) and one patient with Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) syndrome. Additionally, candidate variants in C4B and ITPR3 genes were detected in an additional pedigree.ConclusionsMonogenic SLE was identified in 46% of the children within this selected cohort. A genetic diagnosis can yield direct clinical implications and enhance our understanding of the mechanisms involved in the more common sporadic forms of SLE.

IntroductionLupus podocytopathy (LP) is an under-recognized pathological manifestation in patients with systemic lupus erythematosus (SLE). Despite being a distinct entity, current American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) guidelines do not include specific recommendations about LP, contributing to uncertainty regarding its diagnosis and treatment. This systematic review aims to synthesize the available literature on LP from case reports, case series and retrospective cohort studies to better characterize its clinical course, thereby informing clinical decision-making.Material and methodsA systematic search of EMBASE and MEDLINE was conducted to identify relevant studies. Eligible studies included case reports, case series, and cohort studies reporting SLE patients who had biopsy-proven lupus podocytopathy without features of class III, IV, or V lupus nephritis. Demographic characteristics, clinical presentations, relevant laboratory and pathology results, treatment and outcomes were studied.ResultsThis systematic review included 26 studies (18 case reports/small series and 8 cohorts), analyzing 19 individual cases and 240 cohort patients with LP. Most patients were young females, and LP was often part of the initial lupus manifestation with nephrotic-range proteinuria. Minimal change disease (MCD) was the predominant pathology. Patients with LP had an overall favorable outcome with treatment employing systemic steroid and steroid-sparing agents.ConclusionsLP is an uncommon but distinct manifestation of SLE with overall favorable outcome with treatment using systemic steroid and steroid-sparing agents.