Lupus Science & Medicine最新文献

{"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}

{"title":"Antiphospholipid syndrome in the paediatric population: performance of ACR-EULAR classification criteria in a controlled cohort.","authors":"Stanley Niznik, Daniel Bar, Shiri Spielman, Rotem Semo-Oz, Assaf Barg, Sarina Levy-Mendelovich, Gili Kenet, Nancy Agmon-Levin, Irit Tirosh","doi":"10.1136/lupus-2026-002013","DOIUrl":"10.1136/lupus-2026-002013","url":null,"abstract":"<p><strong>Introduction: </strong>Antiphospholipid syndrome (APS) is a systemic autoimmune disorder marked by thrombotic and non-thrombotic manifestations. In children, diagnosis remains challenging due to lack of validated paediatric criteria. As the 2006 revised Sapporo has been used without validation, and the 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR-EULAR) classification system based on a more modern disease improves specificity; however, their performance and applicability in the paediatric population have not yet been extensively vetted.</p><p><strong>Objective: </strong>This study evaluates the performance of the ACR-EULAR APS criteria in a paediatric cohort of APS and antiphospholipid antibody (aPL) patients, focusing on key diagnostic parameters and comparison with traditional criteria.</p><p><strong>Methods: </strong>A retrospective review of 69 patients' ≤18 years followed at the Sheba Medical Center (2011-2024) was conducted. Clinical, laboratory and serological data including anti-cardiolipin, anti-β2GPI, lupus anticoagulant as well as APS score (adjusted Global Antiphospholipid Syndrome Score, aGAPSS) were analysed. Patients were divided into APS patients (n=29) or aPL carriers (controls; n=40). APS diagnosis was made based on expert opinion and validated by two independent experts.</p><p><strong>Results: </strong>In our cohort (mean age 16 years; 62% female). APS diagnosis was more common among those with a family history of APS (37.5% vs 17.5%; p=0.056). Comparing APS patients and aPL carriers, unprovoked venous thrombosis (OR 1.55, 95% CI 1.02 to 2.36) and aGAPSS OR 1.053 (1.031 to 1.076) and platelet number (OR 0.999, 95% CI 0.998 to 1) were the strongest predictors of APS. Moreover, non-thrombotic manifestations such as heart valve disease, livedo reticularis and diffuse alveolar haemorrhage were only present in the APS group. Catastrophic APS rate was 10.3% among our APS group. Mortality rate was 6.7% among APS group and 0% among aPL carriers.In the paediatric population, the 2023 ACR/EULAR criteria demonstrated superior diagnostic performance compared with the 2006 Sapporo criteria, characterised by a higher positive likelihood ratio (18.23 vs 16.43) and a lower negative likelihood ratio (0.036 vs 0.136), effectively improving both the rule-in and rule-out capacity for APS diagnosis.</p><p><strong>Conclusions: </strong>The superior sensitivity and likelihood ratio of the 2023 ACR-EULAR criteria suggest they may be a valuable tool for the classification of paediatric APS; however, further prospective validation is essential to optimise their clinical application.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352437","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":"Increasing the utilisation of hydroxychloroquine blood level testing in lupus: a quality improvement project.","authors":"Zeinab Saleh, Elizabeth Spranger, Sarah Smeets-Parmelee, Joanne Michelle Kahlenberg, Carmen Gherasim, Catherine Slomiany, Maya Aravind, Roni M Shtein, Shqipe Selman, Rebeca Packard, Tammy Ellies, Anita Devine, Wendy Marder, Emily C Somers","doi":"10.1136/lupus-2026-002113","DOIUrl":"10.1136/lupus-2026-002113","url":null,"abstract":"<p><strong>Objective: </strong>Hydroxychloroquine (HCQ) is a cornerstone therapy for SLE, reducing flares, organ damage and mortality. However, weight-based dosing yields highly variable drug exposure, which can result in suboptimal treatment. Measuring HCQ blood levels provides an objective tool to assess adherence and guide individualised dosing. Although available at our academic medical centre, this testing remains infrequently ordered in routine practice. We aimed to increase HCQ testing in patients with SLE through a structured quality improvement initiative and to characterise the clinical distribution of HCQ level results among tested patients.</p><p><strong>Methods: </strong>We conducted a single-centre quality improvement project from August 2024 to November 2025 using a Plan-Do-Study-Act framework. Interventions included multidisciplinary education, development of institutional guidelines and implementation of an order set incorporating HCQ testing at prescribing. The primary outcome was the proportion of eligible patients with SLE with HCQ testing. As a secondary analysis, HCQ level results were categorised into four clinically meaningful ranges (severe non-adherence, subtherapeutic, therapeutic and supratherapeutic) based on published literature.</p><p><strong>Results: </strong>Among nearly 1000 adult patients with SLE, HCQ testing increased from 4% to 15% (absolute increase of 11 percentage points; more than threefold relative). Provider adoption increased from 24% (8/33) to 73% (24/33) of rheumatologists. Among 170 tested patients, 79.4% had HCQ levels below the therapeutic range, including 14.7% with severe non-adherence (<200 ng/mL), approximately twice that in published cohorts.</p><p><strong>Conclusions: </strong>This real-world quality improvement initiative demonstrates both the feasibility and clinical yield of integrating HCQ monitoring into routine SLE care. Beyond increasing test utilisation, monitoring revealed a substantial burden of HCQ exposure below the therapeutic range that would have remained invisible without systematic testing. The model is readily adaptable to other centres, particularly those serving populations facing access barriers.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352385","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 exercise interventions on core health outcomes in patients with SLE: systematic review and meta-analysis.","authors":"Zehui He, Shuqi Jia, Mengsi Chen, Xinxin Shi, Lunuo Hu, Fei Li, Hui Shi, David C Nieman, Yue Shi","doi":"10.1136/lupus-2026-002027","DOIUrl":"10.1136/lupus-2026-002027","url":null,"abstract":"<p><strong>Objectives: </strong>This meta-analysis evaluated the effects of exercise interventions on key health outcomes in adults with SLE, including fatigue, physical function, aerobic capacity, disease activity, depression and pain.</p><p><strong>Methods: </strong>Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched four databases up to February 2025 for randomised controlled trials (RCTs) in adults diagnosed with SLE according to the American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria. Eligible studies examined aerobic, resistance or combined exercise as the sole intervention. Meta-analyses were conducted using Hedges' g, the Risk of Bias 2 (ROB-2) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system used to assess bias and evidence quality.</p><p><strong>Results: </strong>Twelve RCTs involving 470 participants were included. Exercise showed small-to-moderate improvements in fatigue (g=-0.53, 95% CI -0.81 to -0.25, p<0.001), physical function (g=0.46, 95% CI 0.23 to 0.68, p<0.001), aerobic capacity (g=0.47, 95% CI 0.22 to 0.71, p<0.001), depression (g=-0.36, 95% CI -0.64 to -0.09, p=0.01) and pain (g=-0.53, 95% CI -0.86 to -0.20, p<0.001), with no significant change in disease activity (g=0.18, 95% CI -0.16 to 0.51, p=0.30). Subgroup analyses suggested greater benefits with moderate-intensity programmes lasting 8-12 weeks. GRADE rated the evidence as moderate for fatigue, physical function, depression and pain, and low for other outcomes.</p><p><strong>Conclusion: </strong>Exercise is an effective non-pharmacological therapy in SLE management, improving several physical and psychological outcomes. Individualised, moderate-intensity and supervised programmes are recommended. Further research should optimise intervention protocols and evaluate long-term safety.</p><p><strong>Prospero registration number: </strong>CRD420251115953.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352376","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":"Old marker, new face: anti-RNP as a sentinel of coronary and peripheral endothelial dysfunction in systemic lupus erythematosus.","authors":"Amany M Ebaid, Mona Rabie, Wedad Mahmoud Ghazy, Shaimaa Wageeh, Mohammad Eltahlawi, Doaa Alhssein Abo-Alella, Wafaa Metwally, Basma Magdy Elkholy, Lobna I Kotb","doi":"10.1136/lupus-2026-002125","DOIUrl":"10.1136/lupus-2026-002125","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between anti-ribonucleoprotein (anti-RNP) antibodies and endothelial dysfunction (ED) in patients with SLE and their ability to predict early ED manifestations, both coronary and peripherally.</p><p><strong>Methods: </strong>A cross-sectional study was conducted at a tertiary hospital involving 70 patients with SLE meeting American College of Rheumatology (ACR)/Systemic Lupus International Collaborating Clinics (SLICC) criteria. All study participants underwent a full clinical and laboratory evaluation, including testing for Cardiovascular Diseases serum anti-RNP antibodies. Conventional transthoracic 2-dimensional echocardiography, tissue Doppler imaging and a transthoracic dobutamine stress echocardiography to assess coronary microvasculature by measuring coronary flow velocity reserve (CFVR). Peripheral microvascular morphology was evaluated via nailfold dermoscopy. The primary outcome measures were the mean CFVR values and the presence of dermoscopic abnormalities (capillary drop-out, tortuosity and density) in relation to anti-RNP titres.</p><p><strong>Results: </strong>In 70 patients with SLE, those with high disease activity (n=45) exhibited significantly impaired cardiac function compared with low-activity patients (n=25), showing lower ejection fraction (EF) and CFVR, alongside higher Wall Motion Score Index (p<0.05). Anti-RNP levels correlated positively with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI, r=0.653, p<0.001), erythrocyte sedimentation rate, proteinuria and Raynaud's phenomenon. Significant negative correlations existed between anti-RNP and stress EF (r=-0.33), CFVR (r=-0.30), C3 and C4 (p<0.05). Furthermore, elevated anti-RNP levels were significantly associated with clinical manifestations such as myositis and avascular necrosis, as well as dermoscopic microvascular changes, including microhaemorrhage and capillary dropouts (p<0.05).</p><p><strong>Conclusions: </strong>High anti-RNP titres are significantly associated with subclinical coronary microvascular impairment and peripheral capillary architectural changes in SLE. These results suggest that anti-RNP acts as a sentinel marker for early ED, providing potential for improved cardiovascular risk stratification independent of traditional risk factors.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352430","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":"Type I interferons enhance B cell activation and promote differentiation of double negative 2 cells in SLE.","authors":"Zoha Faheem, Giselle M Boukhaled, Carol Nassar, Kieran Manion, Michael Kim, Dennisse Bonilla, Dafna D Gladman, Laura Whittall Garcia, Zahi Touma, David G Brooks, Joan Wither","doi":"10.1136/lupus-2026-002042","DOIUrl":"10.1136/lupus-2026-002042","url":null,"abstract":"<p><strong>Objectives: </strong>SLE is characterised by unpredictable flares and periods of quiescence. Currently, the mechanisms driving flares remain incompletely understood. Type I interferon (IFN) signalling is strongly implicated in SLE pathogenesis and promotes expansion of age-associated B cells in murine lupus, which are phenotypically similar to double negative 2 (DN2) B cells in humans. We investigated how IFN exposure influences B cell activation and differentiation in SLE, and whether type I IFN promotes DN2 differentiation in human naïve B cells in vitro.</p><p><strong>Methods: </strong>A cytometry by time of flight panel was developed to identify B cell subsets, markers associated with B cell activation and IFN-stimulated proteins (ISPs), with a composite ISP score used as a surrogate for IFN exposure. Peripheral blood mononuclear cells from 18 healthy controls (HCs), 25 quiescent patients and 41 recently flaring patients with SLE were analysed. HC naïve B cells were stimulated under conditions that promote or inhibit DN2 differentiation with and without IFNs.</p><p><strong>Results: </strong>All B cell subsets exhibited higher ISP levels in flaring than quiescent disease. DN2 cells were more abundant in flaring patients and correlated with the ISP score. ISP scores strongly correlated with markers associated with B cell activation even after controlling for disease status. In vitro, IFNα and IFNβ promoted DN2 differentiation in HC B cells. In patients treated with the type I IFN receptor-blocking therapy anifrolumab, DN2 frequency and ISP scores significantly decreased.</p><p><strong>Conclusions: </strong>Type I IFN promotes human B cell activation and DN2 differentiation, supporting IFN blockade as a strategy to reduce pathogenic B cells and prevent SLE flares.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352401","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 of a LASSO-based machine learning model for relapse prediction in lupus nephritis.","authors":"Hao Liu, Yan Zheng, Jin Ding, Ying Li, Jinghua Wang, Wenjuan Zhang, Zhaohui Zheng","doi":"10.1136/lupus-2026-002003","DOIUrl":"10.1136/lupus-2026-002003","url":null,"abstract":"<p><strong>Objective: </strong>To identify the predictors of renal relapse in patients with lupus nephritis (LN) and develop a predictive model.</p><p><strong>Methods: </strong>The patients with LN who received renal biopsies from 2005 to 2024 in Xijing Hospital were enrolled. This study was designed as a cohort study. Clinical and serological characteristics at the time of renal biopsy, nephritis histology, the duration to remission and treatment regimen were evaluated. Variables were screened using least absolute shrinkage and selection operator (LASSO)-Cox analyses, followed by the application of multivariate Cox regression to construct a relapse risk prediction model. The performance of the model was evaluated using bootstrap resampling. A landmark analysis was performed at 12 months, excluding patients who relapsed within this period. The model is intended for application at the 12-month postbiopsy time point.</p><p><strong>Results: </strong>A total of 831 patients were enrolled in the study, 225/831 patients (27.08%) experienced relapse. Compared with the patients without relapse, patients with relapse demonstrated younger age of onset (24.0 vs 27.0 years, p=0.001), higher SLE Disease Activity Index (SLEDAI) (12.0 vs 7.0, p=0.001) and proteinuria (1.2 vs 0.6 g/day, p=0.001). However, the nephritis histology showed no significant difference between the two groups. The proportion of patients receiving intravenous methylprednisolone pulse therapy or belimumab in the non-relapse group was significantly higher. Using LASSO-Cox regression, four variables associated with LN relapse were identified, including level of 24-hour proteinuria, SLEDAI 2000 (SLEDAI-2K), low complement C3 level and remission within 12 months. The predictive model exhibited good predictive performance, with a bootstrap-corrected C-index of 0.75 (95% CI 0.72 to 0.79).</p><p><strong>Conclusions: </strong>Higher level of 24-hour proteinuria, higher SLEDAI-2K score and low complement C3 level were risk factors for LN relapse, while remission within 12 months was a protective factor. The LASSO-Cox-based predictive model exhibited good performance and may serve as a useful tool for the clinical management of LN.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330580","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}