Lupus Science & Medicine最新文献

{"title":"Integrated immune profiling identifies a coordinated T-cell activation and inflammatory signature in SLE.","authors":"Katarzyna A Lisowska, Michał Komorniczak, Martyna Misztal, Barbara Bullo-Piontecka, Alicja Dębska-Ślizień, Agnieszka Jankowska-Kulawy, Anna Wardowska","doi":"10.1136/lupus-2026-002068","DOIUrl":"10.1136/lupus-2026-002068","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with SLE have an increased risk of infections and infection-related mortality, which may be associated with disturbances in immune cell populations. Despite extensive research, findings regarding T-cell and B-cell alterations in SLE remain inconsistent. Therefore, we analysed peripheral blood immune cell subpopulations and their molecular profiles in patients with SLE with renal involvement compared with healthy controls (HCs).</p><p><strong>Methods: </strong>The phenotype and gene expression of lymphocytes from patients with SLE and lupus nephritis and healthy donors were assessed using flow cytometry and quantitative PCR. Exploratory multivariate and treatment-sensitivity analyses were performed to evaluate global immune patterns and potential treatment-related confounding.</p><p><strong>Results: </strong>Patients with SLE exhibited a decreased proportion of helper T (Th) cells and an increased percentage of cytotoxic T (Tc) cells compared with HC, accompanied by a reduced CD4/CD8 ratio. The percentages of CD4⁺CD28⁺ and CD8⁺CD28⁺ T cells were lower and correlated with disease duration, whereas the proportions of activated HLA-DR⁺ Th and Tc cells were increased. Serum interleukin (IL)-6 and IL-10 levels were elevated in patients with SLE. In addition, both T and B cells displayed increased expression of genes associated with inflammatory and interferon-related responses, including TBX21, APOBEC3G, IRF8 and ISG15. Exploratory multivariate profiling suggested coordinated immune activation patterns in SLE, characterised by enhanced T-cell activation, elevated inflammatory cytokines and plasmablast expansion, alongside reduced CD28⁺ T-cell subsets. Treatment-sensitivity analyses indicated that selected immune parameters may be influenced by glucocorticoid exposure and disease duration.</p><p><strong>Conclusions: </strong>Patients with SLE with renal involvement show coordinated disturbances in T-cell and B-cell compartments linked to chronic immune activation, interferon-related responses and disease duration. These findings support the relevance of integrated immune profiling in SLE but should be interpreted as exploratory and require validation in larger longitudinal cohorts.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456224","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":"International development of a lupus-specific instrument to assess cognitive symptoms in patients with SLE: Lupus Brain Fog Severity Scale (LBFSS) study.","authors":"Laurent Arnaud, Matteo Piga, Guillermo J Pons-Estel, Yurilis J Fuentes-Silva, Hervé Devilliers, Raquel Faria, Ali Duarte-Garcia, Daniel Guimarães de Oliveira, Marina Scolnik, Sander van Leuven, Eve Smith, Simone Appenzeller, Ivan Padjen, Michelle A Petri, Alessandra Bortoluzzi, Ioannis Parodis, Meggan Mackay, Faisal Parlindungan, Odirlei A Monticielo, Antonis Fanouriakis, Catherine Kleitz, Andrea M Knight, Nathalie Philippi, Alberta Hoi, Zoe Karakikla-Mitsakou, Sofia Silva Ribeiro, Annemarie Sluijmers, Aldevina Sturiene, Zahi Touma","doi":"10.1136/lupus-2026-002148","DOIUrl":"10.1136/lupus-2026-002148","url":null,"abstract":"<p><strong>Introduction: </strong>Cognitive symptoms such as 'brain fog' are frequent and disabling in patients with SLE. We aimed to develop and validate the Lupus Brain Fog Severity Scale (LBFSS), the first patient-reported outcome measure (PROM) for cognitive symptoms in SLE.</p><p><strong>Methods: </strong>The LBFSS was developed using a multi-step international approach involving healthcare professionals and patients with SLE. Patients provided free-text descriptions of brain fog, generating candidate domains through thematic analysis (step 1). Domains were rated for relevance (step 2) and those retained converted into self-assessable items (step 3). The pilot LBFSS was iteratively refined (step 4). The finalised LBFSS was validated (step 5) in a large international SLE cohort. Psychometric evaluation included internal consistency, exploratory factor analysis and assessment of construct, convergent, known-groups and criterion-related validity.</p><p><strong>Results: </strong>In step 1, 147 SLE participants across 39 countries generated 21 domains for cognitive symptoms, of which 13 were retained in consensus (step 2), converted into self-assessable items (step 3) and iteratively refined using patient and physician feedback. In step 5, validation of the LBFSS instrument in 378 patients from 36 countries demonstrated high internal consistency (Cronbach's α=0.95) and a unidimensional structure explaining 62.2% of variance. LBFSS scores were significantly higher in participants reporting brain fog (p<0.0001), confirming known-group validity. Construct validity was supported by significant correlations with functional impact and symptom severity (ρ=0.46-0.65, p<0.0001), strong convergent validity with the Perceived Deficits Questionnaire-20 (ρ=0.84, p<0.0001) while the discriminative performance for presence versus absence of self-reported brain fog was high (area under the curve=0.85).</p><p><strong>Conclusion: </strong>The LBFSS is a new, valid and feasible PROM to assess brain fog and cognitive symptoms in SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13365746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437254","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":"Real-world experience with personalised belimumab spacing in sustained SLE remission: a multicentre study.","authors":"Alice Bartoletti, Lorenza Maria Argolini, Giuseppe Alvise Ramirez, Luca Moroni, Tommaso Schioppo, Chiara Bellocchi, Sofia Aliprandi, Biancamaria Venerandi, Annalaura Fasiello, Gabriele Domenico Gallina, Lorenzo Beretta, Lorenzo Dagna, Roberto Caporali, Maria Gerosa","doi":"10.1136/lupus-2026-002015","DOIUrl":"10.1136/lupus-2026-002015","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the feasibility and safety of belimumab dose spacing and withdrawal in patients with SLE in long-standing remission on belimumab.</p><p><strong>Methods: </strong>Patients with SLE fulfilling the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria who underwent belimumab spacing and/or discontinuation were identified across four tertiary rheumatology centres. The shared belimumab step-down strategy consisted of spacing to subcutaneous (SC) 200 mg/10 days (or intravenous (IV) 10 mg/kg/6 weeks). In the absence of flares, belimumab could be progressively tapered every 6-12 months to SC 200 mg/14 days (or IV 10 mg/kg/8 weeks), SC 200 mg/21 days (or IV 10 mg/kg/12 weeks), SC 200 mg/28 days (or IV 10 mg/kg/16 weeks) and eventually discontinued.</p><p><strong>Primary endpoint: </strong>SLE flares occurrence.</p><p><strong>Results: </strong>Among 152 patients with SLE treated with belimumab, 22 (14.5%) underwent spacing for sustained remission (21 females (95.5%), mean±SD age 47±11 years). Spacing patients had longer mean remission duration compared with standard-dose belimumab (67±30 vs 33±32 months, p<0.001), less serological activity (low complement and/or positive anti-double stranded DNA 31.8% vs 54.6%, p=0.048), lower SLE Disease Activity Index 2000 (0.77±1.23 vs 1.98±2.01, p<0.001) and were less often on glucocorticoids (22.7% vs 47.7%, p=0.029) or additional immunosuppressants (0.0% vs 50.8%, p<0.001). During the 21±5.4 months of follow-up, no SLE flares occurred. None of the patients required glucocorticoid dose escalation or reduced the dose interval. Seven patients discontinued belimumab.</p><p><strong>Conclusion: </strong>Progressive belimumab dose spacing and withdrawal, coupled with clinical monitoring, could be a practicable approach in selected patients with SLE with long-standing disease remission on minimal glucocorticoid doses, no additional immunosuppressants and low serological activity.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422219","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":"Qualitative interview study in patients with SLE to assess patient perception of fatigue and skin-related symptoms.","authors":"Joseph F Merola, Victoria P Werth, Jiyoon C Choi, Brandon Becker, Teresa Edwards, Coburn Hobar, Samantha Pomponi, Laurie Eliason, Vibeke Strand","doi":"10.1136/lupus-2025-001898","DOIUrl":"10.1136/lupus-2025-001898","url":null,"abstract":"<p><strong>Objective: </strong>SLE is a chronic autoimmune disorder with a range of symptoms. While these are broadly reported in the literature, the symptom impact of SLE on patient health-related quality of life is less well documented. This qualitative interview study aimed to understand the nature and importance of skin symptoms, evaluate the content validity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale in SLE and assess what constitutes meaningful change in SLE-associated fatigue and skin symptoms.</p><p><strong>Methods: </strong>In August 2023, 60 min individual interviews were conducted virtually with 18 adults in the USA who self-reported a diagnosis of SLE and reported experiencing SLE-related fatigue within the prior 30 days. 17 participants also reported experiencing SLE-related skin symptoms. Participants described their experiences with these symptoms and their perceptions of the smallest meaningful improvement using their own words and using the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales. Cognitive debriefing was conducted to evaluate content validity of the 13-item FACIT-Fatigue scale (V.4) for SLE-related fatigue.</p><p><strong>Results: </strong>Of the 18 participants interviewed (mean age 51.7 years (range 33-67 years)), 17 were female and nine were white. All participants acknowledged that all items of the FACIT-Fatigue scale were relevant to SLE-related fatigue and most could comprehend and answer all items without difficulty. 13 participants indicated that a one-point improvement in fatigue on the PGIS would be meaningful. All participants with skin symptoms understood the skin-specific PGIS and PGIC items without difficulty. A one-point improvement on the PGIS and 'a little better/moderately better' on the PGIC represented meaningful improvements in skin symptoms by most participants.</p><p><strong>Conclusion: </strong>These results support the use of the FACIT-Fatigue scale in SLE trials and suggest that even minimal improvements in fatigue and skin symptoms are meaningful to patients.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404995","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":"Upadacitinib enhances platelet procoagulant responses in a subset of healthy individuals and patients with SLE: a pilot study.","authors":"Veronica Tsegai, Halimat Lawal, Cini John, Ibukun Akinrinade, Stella Duncan, Antoine Dufour, Claire E H Barber, Glen Hazlewood, May Y Choi, Ejaife O Agbani","doi":"10.1136/lupus-2026-001983","DOIUrl":"10.1136/lupus-2026-001983","url":null,"abstract":"<p><strong>Background: </strong>Janus kinase inhibitors (JAKis) are emerging therapies for SLE, but concerns regarding thromboembolic risk persist. Clinical trials in SLE have not consistently demonstrated an increased risk of thrombotic events and the effects of JAK inhibition on platelet function remain incompletely understood.</p><p><strong>Objectives: </strong>To investigate whether the JAK1 inhibitor upadacitinib modulates platelet procoagulant membrane dynamics (PMD) in vitro and to explore the associated cytokine signatures.</p><p><strong>Methods: </strong>Whole blood from patients with SLE (n=10) and healthy controls (n=10) was preincubated with upadacitinib (0, 60 and 300 ng/mL). Platelet-rich plasma was analysed using confocal microscopy and Volocity software (Quorum Technology) to quantify PMD markers. We used Alexa Fluor 488 CD62p to detect degranulation, Alexa Fluor 568 Annexin-V to detect phosphatidylserine exposure and Alexa Fluor 647 PAC-1 to detect integrin αIIbβ3 activation. Participants were stratified as JAKi-activated or JAKi-null depending on whether PMD markers were amplified on JAK inhibition or remained unaffected. We then used Luminex xMAP technology to quantify 96 human plasma cytokines, chemokines and growth factors.</p><p><strong>Results: </strong>Platelet responses were heterogeneous. Approximately 30% of both groups exhibited increased platelet activation and procoagulant responses ('JAKi-activated'), whereas the remainder remained unaffected. Platelets of patients with SLE demonstrated elevated baseline activation, characterised as preactivation or autoactivation. JAKi-activated phenotypes were associated with increased plasma levels of interleukin (IL)-4 and tumour necrosis factor-beta (TNF-β) after JAK inhibition. In vitro, we showed that recombinant IL-4 and TNF-β directly activated platelets or primed platelet responses to procoagulant agonists, supporting a potential indirect mechanism for the enhanced procoagulation observed in our JAKi-activated subpopulations.</p><p><strong>Conclusions: </strong>Upadacitinib was associated with enhanced platelet activation and procoagulant responses in vitro in a subset of individuals with SLE and healthy controls. These findings are preliminary and hypothesis-generating. Further studies are required to determine clinical relevance and validate stratification approaches.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405069","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":"Development and validation of a lectin-based assay for detection of IgG Fc glycosylation as a biomarker in lupus nephritis.","authors":"Rohit Upadhyay, Juan Gao, Alexia M Michelle Orellana Enamorado, Scott E Wenderfer, George C Tsokos, Rhea Bhargava","doi":"10.1136/lupus-2026-002059","DOIUrl":"10.1136/lupus-2026-002059","url":null,"abstract":"<p><strong>Background: </strong>Lupus nephritis (LN) is a devastating complication of systemic lupus erythematosus (SLE). Aberrant IgG glycosylation drives podocyte injury and is a robust marker for LN. The primary method for detecting glycosylation is limited to mass spectrometry, but it is not suitable for clinical applications due to its complexity and high cost.</p><p><strong>Methods: </strong>We developed and optimised a lectin-based enzyme-linked assay to detect IgG glycan residues. Lectins were selected based on the glycan structures detected in a SLE cohort and were differentially expressed in SLE with and without nephritis. 96-well plates were coated with protein L. Blocking solutions for each lectin were selected from 5% bovine serum albumin (BSA), deglycosylated BSA (deBSA) and carbo-free blocking solution. IgG standards range was optimised starting from 0 to 20 µg/mL. Fucose was detected by <i>Aleuria aurantia</i> lectin (AAL), galactose was detected by <i>Erythrina crista-galli</i> lectin (ECL) and sialic acid was detected by <i>Sambucus nigra</i> lectin (SNA). An SLE cohort was used to test the ability of these novel assays to differentiate patients with LN from non-renal SLE.</p><p><strong>Results: </strong>The selected lectins produced reproducible standard curves with strong linearity. ELISA assays performed using IgG from a healthy donor, and a patient with LN revealed glycan differences that were consistent with mass spectrometry data and within range of the standard curves. While the AAL (fucose) binding did not differ among different SLE subgroups, ECL (galactose) binding showed significant differences in patients with active LN compared with those with active non-renal SLE and quiescent disease. SNA (sialic acid) binding also distinguished patients with active LN from those with quiescent SLE; however, it did not discriminate between renal and non-renal SLE.</p><p><strong>Conclusions: </strong>The developed lectin-ELISA assay can detect glycosylation characteristics of IgG in a more cost-effective, clinically applicable manner compared with mass spectrometry. Our validation data suggest the potential of ECL binding assays to help diagnose and monitor patients with LN.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376138","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":"Remission and low disease activity state in childhood-onset systemic lupus erythematosus: differential impact on damage accrual in a Latin American cohort (GLADEL).","authors":"R Ezequiel Borgia, Manuel F Ugarte-Gil, Deborah M Levy, Guillermo J Pons-Estel, Guillermina B Harvey, Lucia Hernández, Luis Alberto Ramírez Gómez, Oscar Uribe-Uribe, Hugo Grisales Romero, Mario Cardiel, Daniel Wojdyla, Graciela S Alarcon, Bernardo A Pons-Estel","doi":"10.1136/lupus-2026-001989","DOIUrl":"10.1136/lupus-2026-001989","url":null,"abstract":"<p><strong>Objective: </strong>To examine the impact of different disease activity states (DAS) on outcomes in a longitudinal inception childhood-onset SLE cohort.</p><p><strong>Materials and methods: </strong>Three DAS were included-remission: clinical SLE DAS (SLE Disease Activity Index (SLEDAI)=0, prednisone (≤5 mg/day) and/or immunosuppressants (IS) (maintenance dose)); lupus low DAS (LLDAS): SLEDAI ≤4 with 0 scores for major organ involvement, no increase in any SLEDAI component since the previous visit, on prednisone (≤7.5 mg/day) and/or IS (maintenance dose); and active disease otherwise. The association of these DAS with new damage (increase of at least 1 point in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI)), severe new damage (an increase of ≥3 points in the SDI) and mortality (any cause) at any time during the follow-up was examined using Cox proportional hazards regression models.</p><p><strong>Results: </strong>The majority of the 212 patients included had active disease at baseline (84%). There was no association between LLDAS and lower risk of new damage or severe new damage (HR 0.98, 95% CI 0.43 to 2.22, p=0.955 and HR 0.40, 95% CI 0.04 to 3.62, p=0.415, respectively). Remission was associated with lower risk of new damage (HR 0.36, 95% CI 0.15 to 0.91, p=0.030), but it had no impact on mortality (HR 0.45, 95% CI 0.06 to 3.66, p=0.454).</p><p><strong>Conclusions: </strong>Attaining LLDAS and remission was lower in our cohort than in other contemporary paediatric lupus cohorts. Remission but not LLDAS was associated with lower risk of new damage over 4.3 years of follow-up. None of these DAS were associated with mortality.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376142","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":"Anti-endothelin receptor A autoantibodies associate with immunovascular risk and activate endothelial signalling in SLE.","authors":"Marice K McCrorey, Helen M Butler, Marie Elaine Zehntner, Elizabeth Rainone, Marharyta Semenikhina, Ryan S Lacey, C Alex Colvert, Kennedy P Hawkins, Oleg Palygin, Yasir Abdul, Adviye Ergul, Melissa A Cunningham, Jim C Oates, Justin P Van Beusecum","doi":"10.1136/lupus-2026-002117","DOIUrl":"10.1136/lupus-2026-002117","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular disease in SLE is not fully explained by traditional risk factors, supporting a role for disease-specific immunovascular mechanisms. Autoantibodies targeting endothelin receptor A (ET_AR) and endothelin receptor B (ET_BR) have been implicated in vascular injury in other autoimmune diseases, but their clinical and functional relevance in SLE remains unclear. We tested whether ET receptor autoantibodies associate with endothelial activation and directly stimulate ET receptor signalling in SLE.</p><p><strong>Methods: </strong>Plasma anti-ET_AR and anti-ET_BR autoantibodies and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in a pilot cohort of women with SLE and non-SLE controls and in an independent validation cohort stratified by SLE and hypertension (HTN) status. Multivariable models adjusted for demographic variables, blood pressure and medication use. Mechanistic studies were performed in primary human renal endothelial cells (HRECs) using live-cell calcium (Ca²⁺) imaging, ET receptor antagonists and receptor-directed blocking peptides.</p><p><strong>Results: </strong>Anti-ET_AR and anti-ET_BR autoantibodies were elevated in SLE across both cohorts, with the highest level observed in SLE with HTN. Anti-ET_AR demonstrated the strongest association with sVCAM-1 and independently identified women with the highest endothelial activation burden beyond clinical covariates and anti-double-stranded DNA. In primary HRECs, SLE-derived IgG induced Ca²⁺ flux that was attenuated by ET receptor antagonism. Blockade of the ET_AR extracellular loop 2 domain reduced IgG-mediated Ca²⁺signalling, supporting a non-canonical mechanism of endothelial ET_AR activation.</p><p><strong>Conclusions: </strong>Anti-ETAR autoantibodies associate with immunovascular risk and endothelial activation in SLE and directly stimulate endothelial signalling through a non-canonical ETAR-dependent mechanism. These findings support the use of anti-ETAR autoantibodies as clinically relevant biomarkers and potential novel contributors to vascular dysfunction in SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368888","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":"Quantitative mapping of prefrontal oxygenation dysfunction and neuropsychiatric symptoms in patients with systemic lupus erythematosus: a multichannel functional near-infrared spectroscopy study.","authors":"Gengyi Chen, Chenxin Yu, Yifan Yang, Peng Ding, Ruotong Zhao, Ru Bai, Shuang Liu, Guofang Zhang, Shu Li, Xinyu Xu, Yuqi Cheng, Jian Xu","doi":"10.1136/lupus-2026-002009","DOIUrl":"10.1136/lupus-2026-002009","url":null,"abstract":"<p><strong>Objective: </strong>Neuropsychiatric complications of systemic lupus erythematosus (SLE) lack relevant biological indicators that can be dynamically monitored. This study aims to break the technical barriers of functional near-infrared spectroscopy (fNIRS) in the detection of SLE brain function through methodological innovation and to provide data for establishing relevant biological indicators of neuropsychiatric symptoms in patients with SLE.</p><p><strong>Method: </strong>In this study, the dynamic data of oxyhaemoglobin (HbO) and deoxyhaemoglobin concentrations were obtained by using the spatiotemporal optimisation fNIRS paradigm (verbal fluency task, 60 s task period/10 s dynamic baseline correction) by integrating the verbal fluency task adapted to education and 37-channel fNIRS technology, and the activation effect of each channel in the prefrontal lobe was statistically analysed.</p><p><strong>Result: </strong>The concentration of HbO in the SLE group was significantly lower than that in the healthy controls (HCs) group (p<0.05) on 12 channels (CH13-15, 18, 21-25, 27, 28, 35). Compared with HCs, both the SLE with depression and SLE without depression subgroups showed significantly altered HbO concentrations across 14 channels (CH6, 9, 10, 13-15, 18, 24-28, 34, 36); however, no significant difference was detected between the two SLE subgroups. Compared with the HCs group and SLE without anxiety group, the SLE with anxiety group showed a more severe decrease in HbO concentration (p<0.05) on eight channels (CH6, 10, 13, 17, 18, 24, 25, 26), which were spatially concentrated in the dorsolateral prefrontal cortex and bilateral frontal pole region.</p><p><strong>Conclusion: </strong>Prefrontal HbO oscillation disorder is associated with depressive and anxiety symptoms in SLE patients, and its spatial gradient quantitatively maps the severity of these emotional symptoms during cognitive task engagement, providing a neuroimaging assessment tool that can be implemented at the bedside for neuropsychiatric SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368921","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":"Are RAS inhibitors necessary during intensive immunosuppression for lupus nephritis? Real-world evidence from the STAR cohort.","authors":"Xiaohui Zhang, Xiuli Zhang, Juan Zhao, Yong Fan, Shan Song, Hong Huang, Dai Gao, Lanlan Ji, Zhuoli Zhang","doi":"10.1136/lupus-2026-002025","DOIUrl":"10.1136/lupus-2026-002025","url":null,"abstract":"<p><strong>Objective: </strong>While guidelines advocate renin-angiotensin system inhibitors (RASi) for renoprotection in lupus nephritis (LN), evidence is largely extrapolated from non-lupus populations. Evidence specifically evaluating RASi efficacy during the intensive induction phase of active LN remains scarce. This study aimed to evaluate the real-world impact of adding RASi to standard induction therapy on renal remission and glucocorticoid tapering in LN.</p><p><strong>Methods: </strong>This retrospective cohort study used data from the STAR (Treat-SLE-to-Target) registry. Patients receiving ≥3 months of continuous RASi during induction were classified as RASi, while those without RASi exposure during follow-up were classified as non-RASi. Propensity score overlap weighting was applied to balance baseline characteristics. The primary endpoints were rates of complete renal remission (CRR) at 12 months. Secondary endpoints included total renal remission (TRR), the magnitude and rate of proteinuria reduction and glucocorticoid dosage.</p><p><strong>Results: </strong>Among 314 patients, 220 received RASi and 94 did not. The RASi group had higher baseline 24-hour urinary protein and hypertension prevalence. After weighting, characteristics were balanced. Weighted analyses showed no significant difference in CRR at 12 months (58.7% vs 64.7%, p=0.428) or 6 months (43.1% vs 53.4%, p=0.169). Conversely, 6-month TRR was significantly lower in the RASi group (59.0% vs 76.8%, p=0.026). Proteinuria percentage reduction was comparable between groups, and RASi use was not associated with accelerated glucocorticoid tapering or more rapid decline in disease activity. Multivariable analysis identified LN at SLE onset and baseline pyuria as independent predictors of CRR, but not RASi usage.</p><p><strong>Conclusion: </strong>Adding RASi to standard induction therapy provided no additive benefit for renal remission or proteinuria reduction within the first 12 months nor did it facilitate glucocorticoid tapering. The haemodynamic antiproteinuric effects of RASi appear overshadowed by potent anti-inflammatory treatment during active LN.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361229","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}