Lupus Science & Medicine最新文献

{"title":"Expression pattern and clinical significance of MerTK on circulating NK cells in systemic lupus erythematosus.","authors":"Renge Liang, Ranran Yao, Ziye Wang, Wenwen Pei, Ruyu Liang, Xiao Han, Haojie Xu, Yin Zhu, Jianping Guo, Yin Su","doi":"10.1136/lupus-2024-001407","DOIUrl":"10.1136/lupus-2024-001407","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the clinical significance of Mer receptor tyrosine kinase (MerTK) on circulating natural killer (NK) cells in systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>63 patients with SLE and 36 healthy controls (HCs) were recruited in this study. Peripheral blood samples were collected from all participants. MerTK expression on circulating NK cells (CD3^-CD56⁺) was detected by flow cytometry. MerTK expression was compared between patients with SLE and HCs or lupus nephritis (LN) and non-LN subgroups, and its correlation with clinical or laboratory features was also investigated. Bioinformatic analysis was conducted to explore the potential function of <i>MERTK</i> in NK cells in SLE.</p><p><strong>Results: </strong>MerTK expression on circulating NK cells was significantly higher in patients with SLE than that in HCs. In patients with SLE, NK-cell specific MerTK expression was positively correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), anti-double-stranded DNA antibody levels, proportions and absolute count of B lymphocytes, but negatively correlated with complement C3, complement C4, proportions and absolute count of NK cells. Moreover, NK-cell specific MerTK expression was significantly higher in the LN group than that in the non-LN group. Bioinformatics analysis revealed that <i>MERTK</i> was one of the dysregulated NK-cell related genes in SLE, and the differentially expressed genes related to <i>MERTK</i> were associated with biological pathways including NK cell activation and response to type I interferon (IFN-I). In vitro study showed that MerTK expression on NK cells was increased after IFN-I treatment.</p><p><strong>Conclusions: </strong>The expression of MerTK on circulating NK cells was significantly elevated in patients with SLE, particularly in patients with LN, and was correlated with disease activity and autoantibody titres. <i>MERTK</i> expression may be related to regulation of NK cell activation and induced by IFN-I in SLE. Our findings indicate that circulating NK-cell specific expression of MerTK may play a role in the development and progression of SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of environmentally-induced anxiety on autoimmunity in the MRL/lpr mouse.","authors":"Fan Zhang, Qiong Zhang, Ruo-Nan Dang, Xiao-Xue Tian, Lin-Jie Li, Quan-Min Zhou, Xiao-Ying Li, Yuan-Sheng Wu, Hui-Mei Zou","doi":"10.1136/lupus-2025-001528","DOIUrl":"10.1136/lupus-2025-001528","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the interplay between anxiety disorders and SLE using lupus-prone MRL-lpr mice and MRL/MPJ control mice exposed to predator stress, and to elucidate the potential mechanisms underlying this interaction.</p><p><strong>Methods: </strong>We conducted an experiment where 16 MRL-lpr mice and 16 MRL/MPJ control mice were randomly assigned to four groups and exposed to predator stress (cat exposure) or served as unexposed controls for 2 months. Anxiety levels were evaluated using the elevated plus maze (EPM) and open field test (OFT). Physiological responses were assessed through measurements of body weight, interleukin-6 (IL-6) levels, anti-double-stranded DNA (dsDNA) antibody titres and urine protein content. Additionally, the splenic index and the proportions of regulatory T (Treg) and T helper 17 (Th17) cells were analysed to further understand the immune responses.</p><p><strong>Results: </strong>Both mouse strains exhibited increased anxiety levels as assessed by the EPM and OFT. However, MRL-lpr mice demonstrated a heightened sensitivity to predator stress-induced anxiety compared with MRL/MPJ mice. Biochemical analyses revealed that while MRL/MPJ mice showed a typical inflammatory response to predator stress, characterised by elevated IL-6 levels, this did not exacerbate immune dysregulation or renal damage. In contrast, MRL-lpr mice exhibited markedly increased IL-6 expression, elevated anti-dsDNA antibody levels, higher urine protein content, decreased Treg proportions and increased Th17 proportions in the spleen, suggesting an accelerated progression of lupus disease.</p><p><strong>Conclusions: </strong>Our findings emphasise that lupus-prone MRL-lpr mice display a greater vulnerability to the detrimental consequences of predator stress compared with MRL/MPJ control mice.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of dual-task exercises on cognitive status, disease activity and quality of life in childhood-onset systemic lupus erythematosus.","authors":"Eylul Pinar Kisa, Sezgin Sahin, Gokce Leblebici, İrem Yagmur Tonyali, Gulcin Balci, Şehri Dilek, Esma Aslan, Ela Tarakci, Ozgur Kasapcopur","doi":"10.1136/lupus-2024-001453","DOIUrl":"10.1136/lupus-2024-001453","url":null,"abstract":"<p><strong>Objective: </strong>Many patients with childhood-onset systemic lupus erythematosus (cSLE) suffer from cognitive dysfunction that seriously affects their quality of life, attention, visual and speech memory, motor function, reaction speed and motor perception and physical activity. This study aims to investigate the effects of dual-task (DT) exercises on cognitive status, disease activity and physical function of children with cSLE.</p><p><strong>Method: </strong>30 children with cSLE were included. During intervention sessions (2 days a week for 16 weeks), DT exercises were applied to all children having cSLE. The mental status of the patients by the Montreal Cognitive Assessment (MoCA), pain status by the McGill-Melzack Pain Questionnaire, disease activity by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, physical activity by the Childhood Activity Assessment Index and International Physical Activity Questionnaire (IPAQ) and steps number recorded.</p><p><strong>Results: </strong>McGill-Melzack pain scores and MoCA scores (42.70±16.85 and 20.86±3.89, respectively) were significantly improved after the intervention (36.53±16.55 and 23.73±2.72, respectively) (p<0.05). Additionally, IPAQ median metabolic equivalent scores (3171.73±3185.69) were significantly increased after the intervention (5592.40±6228.61; p=0.01). Lupus disease activity score (SLEDAI-2K) decreased from 2.79±3.20 to 2.18±2.23 with the implementation of DT; however, this was not statistically significant (p>0.05).</p><p><strong>Conclusions: </strong>DT exercises can play a crucial role in enhancing cognitive status and physical function of patients with cSLE. There is limited research examining the effects of DT exercises on cognitive status, particularly in patients with cSLE.</p><p><strong>Trial registration number: </strong>NCT05984316.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of antiphospholipid antibodies on heart valve involvements in systemic lupus erythematosus: based on CSTAR cohort.","authors":"Siyun Chen, Can Huang, Hui Jiang, Yangzhong Zhou, Liying Peng, Ziqian Wang, Junyan Qian, Wei Bai, Shangzhu Zhang, Chuhan Wang, Yuan Zhao, Xiaoxiao Guo, Mengtao Li, Xiaofeng Zeng, Jiuliang Zhao, Yan Zhao","doi":"10.1136/lupus-2025-001674","DOIUrl":"10.1136/lupus-2025-001674","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the role of antiphospholipid antibodies (aPLs) in patients with SLE with heart valve diseases (HVDs).</p><p><strong>Methods: </strong>This prospective study included consecutive patients with SLE who visited Peking Union Medical College Hospital between April 1999 and December 2024. Echocardiography was performed based on clinical indications. Clinical characteristics, aPL profiles and echocardiographic findings were collected. Logistic regression was used to evaluate associations between aPLs and HVD.</p><p><strong>Results: </strong>Among 508 patients with SLE, 27.4% had HVD. The most frequently affected valves were aortic (17.3%) and mitral (11.2%) valves, with thickening (19.5%) and regurgitation (15.9%) as the leading lesion types. aPLs positive patients with SLE had higher rates of HVD (35.1% vs 24.0%, p=0.010), including valve thickening (25.3% vs 16.9%, p=0.028), regurgitation (24.7% vs 12.1%, p<0.001), vegetations (9.1% vs 0.8%, p<0.001) and stenosis (1.9% vs 0.0%, p=0.008). Anticardiolipin-IgG was associated with HVD (OR=2.484, p=0.003), mitral lesions (OR=4.156, p<0.001), valve thickening (OR=2.255, p=0.011) and regurgitation (OR=2.121, p=0.014). Anti-β2 glycoprotein I-IgG showed similar associations and was also linked to valve stenosis (OR=11.209, p=0.022). Lupus anticoagulant (LA) was associated with valve vegetations (OR=8.659, p<0.001) and interventional/surgical indications (OR=6.868, p=0.005).</p><p><strong>Conclusion: </strong>aPLs, especially IgG isotype and LA, are independently associated with diverse HVD in SLE. Echocardiographic monitoring is warranted in aPL-positive patients.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Failing maternal-fetal tolerance in SLE (FaMaLE): a prospective cohort study for finding the molecular mechanisms behind pregnancy complications.","authors":"Wendy Dankers, Jikke F van Ruitenbeek, Serife Asya Germe, Agner R Parra Sánchez, Mirte F H M van Gaal, Marjolein Hortensius, Kyra Cramer, Daphne C Rohrich-Heldens, Marjon de Boer, Lisa G M van Baarsen, Irene E M Bultink","doi":"10.1136/lupus-2025-001668","DOIUrl":"10.1136/lupus-2025-001668","url":null,"abstract":"<p><strong>Introduction: </strong>Pregnant women with SLE have an increased risk of maternal complications and adverse fetal outcomes. These include pre-eclampsia, preterm birth and fetal growth restriction. Interestingly, this increased risk persists in subsequent pregnancies, whereas it decreases in healthy women due to the development of maternal-fetal tolerance. As maternal-fetal tolerance is crucial for a healthy pregnancy, we hypothesise that its failure contributes to the increased risk of pregnancy complications in women with SLE. Therefore, we initiated the failing maternal-fetal tolerance in SLE (FaMaLE) study to investigate the failure of maternal-fetal tolerance in pregnant women with SLE.</p><p><strong>Methods and analysis: </strong>In the FaMaLE study, women with SLE and healthy women are included in their first trimester of pregnancy (<14 weeks gestational age) at Amsterdam UMC. Throughout the pregnancy, data on SLE disease activity, pregnancy course and medication use are collected. Peripheral blood is collected once per trimester, within 48 hours before delivery and 5-12 weeks post partum. In addition, the placenta is collected after delivery. Whole blood, peripheral blood mononuclear cells and placenta samples are freshly analysed by flow cytometry to assess immune cell composition. The resulting data are analysed in relation to SLE disease course, pregnancy course and pregnancy outcomes.</p><p><strong>Ethics and dissemination: </strong>The study has been approved by the Amsterdam UMC Medical Ethics Committee and all participating women will be asked to provide informed consent. The findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and via patient organisations.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of MRI-based brain oxygen extraction fraction mapping in patients with systemic lupus erythematosus.","authors":"Shuoqi Zhang, Jiayi Ma, Shaolong Wu, Ziwei Hu, Su Yan, Junghun Cho, Yi Wang, Lingli Dong, Shun Zhang, Wenzhen Zhu","doi":"10.1136/lupus-2025-001522","DOIUrl":"10.1136/lupus-2025-001522","url":null,"abstract":"<p><strong>Objective: </strong>We aim to assess the cerebral oxygen extraction fraction (OEF) changes in patients with systemic lupus erythematosus (SLE) and neuropsychiatric SLE (NPSLE) by using an MRI-based technique and examine the relationship between OEF and cognition.</p><p><strong>Methods: </strong>43 SLE patients (18 NPSLE and 25 non-NPSLE) and 26 healthy controls (HC) were recruited. Cognitive function was assessed via the Montreal Cognitive Assessment (MoCA). OEF was calculated by quantitative susceptibility mapping plus quantitative blood oxygen level-dependent model (QQ). Whole-brain voxel-wise analysis of OEF was performed. In subcortical grey matter structures, regional OEF values were measured, and their relationship with MoCA scores was explored.</p><p><strong>Results: </strong>Whole-brain voxel-wise analysis revealed significant changes of OEF primarily in the limbic system, including the orbitofrontal cortex and bilateral insular lobes, among HC, non-NPSLE and NPSLE groups. Regional analysis indicated reduced OEF values in subregions of the amygdala, hippocampus and caudate nucleus in non-NPSLE compared with HC, with decreasing trends observed in all selected regions of subcortical grey matter structures. In the right hippocampus, OEF values were increased in NPSLE patients compared with non-NPSLE patients. Considering all subjects in the study, OEF values in the bilateral medial amygdalae, right lateral amygdala, left rostral hippocampus and right dorsal caudate nucleus were positively correlated with MoCA scores.</p><p><strong>Conclusion: </strong>Cerebral OEF mapping in patients with SLE is readily available using the MRI-based QQ method, which has the potential to serve as an adjunctive tool for diagnosing NPSLE and monitoring cognitive impairment in SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary arterial hypertension in systemic lupus erythematosus: identification of risk factors and haemodynamics characteristics in a multicentre retrospective cohort.","authors":"Emiliano Marasco, Christina Düsing, Stefanie Keymel, Alessandra Bortoluzzi, Claudia Bracaglia, Matthieu Canuet, Ilaria Cavazzana, Gamal Chehab, Veronica Codullo, Rebecca Fischer, Franco Franceschini, Micaela Fredi, Stefano Ghio, Lisa Keller, Alain Meyer, Carlomaurizio Montecucco, Jutta Richter, Marianne Riou, Sezgin Sahin, Oliver Sander, Andreas Schwarting, Carlo Alberto Scirè, Ettore Silvagni, Konstantinos Triantafyllias, Giovanni Zanframundo, Lorenzo Cavagna, Matthias Schneider","doi":"10.1136/lupus-2024-001471","DOIUrl":"10.1136/lupus-2024-001471","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of our work was to identify specific patterns in clinical features and nailfold capillary changes that may help in screening for pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>We identified patients with SLE and type I PAH (n=20) without other connective tissue diseases and collected demographic, clinical and laboratory features. We selected as controls patients with SLE who underwent cardiopulmonary screening to exclude PAH (n=87): we collected demographic, clinical and laboratory features and performed nailfold videocapillaroscopy (NVC).</p><p><strong>Results: </strong>All patients with SLE-PAH were women; age and disease duration were not different from patients with SLE without PAH. Lupus anticoagulant (LAC)+and anti-ribonucleoprotein (RNP)+were more prevalent in patients with SLE-PAH (respectively, PAH 45.0% vs no-PAH 20.5%, p=0.042; PAH 45.0% vs no-PAH 19.5%, p=0.035). No differences were observed for anti-Sm, anti-Ro, anti-La and anti-cardiolipin and anti-beta2GPI antibodies. Among clinical features, mucocutaneous and central nervous system involvement were more prevalent in patients with SLE-PAH than in SLE controls (respectively, PAH 65.0% vs no-PAH 34.5%, p=0.024; PAH 25.0% vs no-PAH 8.0%, p=0.046). Raynaud's phenomenon (RP) was more prevalent in patients with SLE-PAH than in SLE controls (PAH 60.0% vs no-PAH 13.8%, p<0.001). RP was a predictor of PAH in patients with SLE (OR 3.8 (0.9-14.8)). We performed NVC on nine patients with PAH and on controls: we observed a significantly higher prevalence of scleroderma pattern at NVC in SLE-PAH than controls (PAH 66.7% vs no-PAH 9.2%, p<0.001). Patients with SLE-PAH showed a lower number of capillary density and a higher frequency of giant capillaries.</p><p><strong>Conclusions: </strong>Our data showed that LAC+, RNP+, RP and a scleroderma pattern at NVC was indicative for patients with SLE-PAH. Our results pointed to generalised microvascular involvement and a hypercoagulation state in patients with SLE-PAH. The variables we identified could be used to implement a screening algorithm to identify patients with SLE at risk of developing PAH.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease.","authors":"Atlas Khan, Gul Karakoc, Ge Liu, Jacy Zanussi, Nancy J Olsen, Mingjian Shi, Nancy J Cox, Jonathan Mosley, Charles Michael Stein, Krysztof Kiryluk, Wei-Qi Wei, Frank Mentch, Scott Hebbring, James Linneman, Vivian Kawai","doi":"10.1136/lupus-2024-001476","DOIUrl":"10.1136/lupus-2024-001476","url":null,"abstract":"<p><strong>Objective: </strong>We defined the genetic factors associated with a positive ANA test (ANA+) in the absence of autoimmune disease and tested the association with SLE.</p><p><strong>Methods: </strong>Using a case-control design, we performed a genome-wide association study (GWAS) in individuals of European ancestry without an autoimmune disease who had ANA tested as part of clinical care from DNA biobanks linked to de-identified electronic medical records: BioVU and Electronic Medical Records and Genomics. GWAS results were meta-analysed and single nucleotide polymorphism (SNP) heritability was calculated. A polygenic risk score (PRS) for ANA+ and for SLE was constructed and compared in patients with SLE, ANA+ and ANA negative (ANA-) individuals without autoimmune disease and general controls who never had ANA testing performed.</p><p><strong>Results: </strong>A total of 7287 individuals of European ancestry were included in the meta-analyses (2169 ANA+ and 5118 ANA-); an SNP upstream of the <i>TSBP1</i> in the HLA locus (rs1967688) was associated with ANA+ (p=4.84×10^-8). SNP heritability for ANA+ was low (h² _SNP= 0.04), and the PRS for ANA+ was not significantly different in ANA+ and ANA- individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p<2.2×10^-16) but did not differ among ANA+, ANA- and general control groups (p=0.17).</p><p><strong>Conclusions: </strong>ANA+ occurring in the absence of autoimmune disease has a genetic association with the <i>HLA</i> region, but overall heritability is low. In addition, few SLE-associated SNPs were associated with ANA+, and the PRS for SLE was not associated with ANA+, indicating limited genetic overlap.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next generation sequencing analysis reveals complex genetic architecture of childhood-onset systemic lupus erythematosus.","authors":"Laura Lewandowski, Linda Hiraki, Christiaan Scott, Ana Barrera-Vargas, Jorge Romo Tena, Diana Gómez-Martín, Michael J Ombrello, Ivona Aksentijevich, Zuoming Deng, Anthony M Musolf, Subrata Paul, Shajia Lu, Massimo Gadina, Daniel Hupalo, Clifton L Dalgard, Sarfaraz Hasni, Earl D Silverman, Mariana J Kaplan","doi":"10.1136/lupus-2024-001475","DOIUrl":"10.1136/lupus-2024-001475","url":null,"abstract":"<p><strong>Objectives: </strong>Our current understanding of the genetic architecture of childhood-onset SLE (cSLE) is limited by a dearth of comprehensive genomic studies in cSLE. We have quantified the number of known rare and common SLE risk variants in a diverse cSLE cohort. We characterised type I interferon (IFN) gene expression scores along with genomic data.</p><p><strong>Methods: </strong>We performed whole genome sequencing on 83 patients with cSLE and 109 unaffected parents and analysed sequences for known common and rare SLE-associated risk variants. Type I IFN gene expression was quantified on a subset of patients. We investigated the relationship between clinical phenotype, genomic profile and type I IFN signatures in this cohort.</p><p><strong>Results: </strong>Patients with cSLE were enriched for common SLE risk variants compared with unaffected parents and controls. We identified rare SLE risk variants in 11% of individuals with cSLE; those with rare variants had earlier disease onset (<12 years) than those without variants. Patients with cSLE had elevated type I IFN gene expression compared with unaffected parents and controls, even though most patients were treated with immunosuppressive therapy.</p><p><strong>Conclusions: </strong>Patients with cSLE from this ancestrally and geographically diverse cohort are enriched for common cSLE risk variants compared with controls, and 11% carry a rare variant in known monogenic SLE risk genes. The relationship between rare and common risk variant burden is more complex than previously hypothesised. Our findings indicate that studying patients with cSLE is important for understanding genetic contributions to SLE pathogenesis.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupus nephritis serum induces changes in gene expression in human glomerular endothelial cells, which is modulated by L-sepiapterin: implications for redox-mediated endothelial dysfunction.","authors":"Dayvia A Russell, Justin P Van Beusecum, Margaret Markiewicz, Sandra M Sanchez, Jeremy L Barth, Jim C Oates","doi":"10.1136/lupus-2025-001568","DOIUrl":"10.1136/lupus-2025-001568","url":null,"abstract":"<p><strong>Objective: </strong>Lupus nephritis (LN) is characterised by renal endothelial dysfunction, which contributes to progressive kidney injury. Endothelial nitric oxide synthase (eNOS) plays a modulating role in LN, as genetic ablation of the eNOS enzyme worsens disease. Serum from patients with active LN induces uncoupling of eNOS homodimers, leading to superoxide (SO) rather than nitric oxide (NO) production by eNOS. This uncoupling is reversed with L-sepiapterin (L-Sep). This study was designed to further examine changes in gene expression in glomerular endothelial cells induced by LN serum and whether treatment with L-Sep can ameliorate these changes.</p><p><strong>Methods: </strong>Primary human renal glomerular endothelial cells (HRGECs) were cultured with serum from healthy controls (HCs), patients with LN during remission (LN rem) or patients with LN during flare (LN flare) with and without L-Sep. Bulk RNA sequencing was performed on RNA isolated from cultured cells. Differential gene expression was determined, and pathway and gene enrichment analyses were performed on differentially expressed genes.</p><p><strong>Results: </strong>L-Sep treatment induced differential gene expression after culture in HRGECs cultured with LN flare serum. Addition of L-Sep induced genes involved in promoting endothelial function and enriched for pathways of NO biosynthetic and metabolic processes, fatty acid and lipid biosynthesis, neurotransmitter biosynthesis, reactive oxygen biosynthesis, vascular endothelial growth factor production and regulation of smooth muscle contraction.</p><p><strong>Conclusions: </strong>These results indicate that glomerular endothelial cells can mount an active inflammatory response in an LN serum environment. More importantly, L-Sep modulates gene expression in a fashion consistent with reduction of oxidative stress and increased NO production. These findings provide the rationale to target endothelial dysfunction to modulate LN with L-Sep as a therapeutic.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}