Lupus Science & Medicine最新文献

{"title":"Influence of sex and systemic lupus erythematosus disease status on cerebral cortex structure.","authors":"Yifan Yang, Li Tao, Ruotong Zhao, Ru Bai, Shuang Liu, Guofang Zhang, Shu Li, Xinyu Xu, Yuqi Cheng, Jian Xu","doi":"10.1136/lupus-2026-002032","DOIUrl":"10.1136/lupus-2026-002032","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the main and interactive effects of sex and disease diagnosis on cortical morphology in systemic lupus erythematosus (SLE), providing neuroimaging evidence for sex-by-disease interactive mechanisms underlying structural brain alterations.</p><p><strong>Methods: </strong>A cross-sectional study design was used to recruit participants. Structural MRI scans were acquired and processed using surface-based morphometry (SBM) to extract cortical thickness (CT), gyrification index (GI), fractal dimension (FD) and sulcal depth (SD) within predefined regions of interest. Two-way analysis of variance assessed main effects and 'sex×diagnosis' interactions (Holm-Bonferroni corrected). Correlation analyses were performed between these structural metrics and SLE disease activity/psychological assessment scores in areas showing significant interactions.</p><p><strong>Results: </strong>196 individuals participated in this study: 30 male SLE patients, 66 female SLE patients, 33 male healthy controls (HC) and 67 female HC. Significant sex-by-disease interactions were detected: SD in left orbital (H-shaped) sulci (S_orbital-H_Shaped) (<i>F</i>=14.8458, p=0.0150), with male HC >male SLE (p=0.0039) and male HC>female HC (p<0.0001), and GI in left middle frontal sulcus (S_front_middle) (<i>F</i>=14.1650, p=0.0313), with female SLE>male SLE (p<0.0001) and male HC>male SLE (p=0.0003). Diagnostic main effects (HC>SLE) were observed extensively for CT across both hemispheres. No significant correlations emerged between disease activity/psychological assessment scores and structural parameters in interaction-significant regions.</p><p><strong>Conclusion: </strong>This study provides novel evidence for sex-by-diagnosis interactive effects in the neuropathological mechanisms of SLE. Sex and SLE disease status have both independent and interacting impacts on cerebral cortical structure.</p><p><strong>Trial registration number: </strong>NCT00703742.</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/PMC13311624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330727","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":"Prognostic value of baseline clinical features in SLE: a cluster analysis.","authors":"Betül Dikkanoğlu Demirok, Sibel Balci, Andaç Komaç, Duygu Temiz Karadağ, Ayşe Çefle, Ayten Yazici","doi":"10.1136/lupus-2026-002008","DOIUrl":"10.1136/lupus-2026-002008","url":null,"abstract":"<p><strong>Objective: </strong>SLE is a heterogeneous systemic autoimmune disease with diverse clinical manifestations. We aimed to identify clinical subgroups of SLE patients using cluster analysis at diagnosis and at the last follow-up and to evaluate their prognostic implications for disease activity, organ damage and mortality.</p><p><strong>Methods: </strong>In this single-centre retrospective cohort study, 199 patients with SLE who fulfilled the 1997 American College of Rheumatology (ACR) classification criteria and were regularly followed at the Rheumatology Clinic of Kocaeli University Hospital were included. Patients were divided into clusters based on their clinical involvement at diagnosis and the last visit using the Gower distance and the Partitioning Around Medoids algorithm. Differences between clusters were assessed using one-way analysis of variance, Kruskal-Wallis and χ² analyses. Analyses were performed using SPSS V.29.0 (IBM Corp, Armonk, New York, USA) and R V.4.3.0.</p><p><strong>Results: </strong>At diagnosis, three clusters were identified: Cluster 1 (n=108) with predominant arthritis; Cluster 2 (n=49) with renal and haematological involvement and highest disease activity (SLE Disease Activity Index 2000, p=0.004); Cluster 3 (n=42) with mucocutaneous manifestations, often accompanied by haematological involvement. After a median follow-up of 168 months, four clusters were identified. Cluster 4', a heterogeneous group with mucocutaneous, articular and renal involvement, had significantly higher Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (SDI) scores (median 4.0 (0-8), p<0.001), indicating poor prognosis. During follow-up, 29.6% of Cluster 1, 22.4% of Cluster 2 and 42.9% of Cluster 3 transitioned to Cluster 4'. Patients with mucocutaneous-predominant disease at diagnosis had a twofold increased risk of transitioning to the poor-prognosis cluster (OR 2.05, 95% CI 1.01 to 4.16, p=0.046). Mortality did not differ significantly between clusters.</p><p><strong>Conclusion: </strong>Cluster analysis based on clinical involvement in SLE can identify homogeneous patient subgroups and predict long-term outcomes. Patients with mucocutaneous-predominant onset, often receiving less intensive treatment, may have a worse prognosis, highlighting the importance of individualised monitoring and management strategies.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148330750","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 determinants of childhood onset systemic lupus erythematosus.","authors":"Meghan Nelson, Shanta Murthy, Sushma Maddipatla, Sreekala Shenoy, Lori Ponder, Shanmuganathan Chandrakasan, Subra Kugathasan, Dave Cutler, Sampath Prahalad","doi":"10.1136/lupus-2025-001874","DOIUrl":"10.1136/lupus-2025-001874","url":null,"abstract":"<p><strong>Introduction: </strong>Childhood-onset systemic lupus erythematosus (cSLE) is associated with significant morbidity and mortality. While numerous variants have been associated with adult-onset SLE, limited data exist on genetic variation within cSLE. We aimed to investigate genetic factors of early-onset cSLE, defined as onset of cSLE prior to age 10.</p><p><strong>Methods: </strong>Employing a case-only design, we performed whole genome sequencing analysis on 37 subjects with early onset cSLE. We hypothesised that rare, functional variants with large effects in genes associated with SLE contribute to the risk of early-onset cSLE and that the polygenic risk score (PRS) would be inversely associated with age of onset and presence of nephritis. A total of 153 linkage disequilibrium-independent variants were analysed and compared with previously reported SLE single-nucleotide polymorphisms. Rare (minor allele frequency (MAF) ≤1%), damaging protein-altering (Combined Annotation Dependent Depletion; CADD≥20) variants, including variants isolated to previously reported monogenic SLE genes (n=49), were prioritised for secondary analysis.</p><p><strong>Results: </strong>37.8% of our cSLE cohort carried at least one rare, pathogenic variant in monogenic SLE genes. We identified 31, 012 rare, damaging, pathogenic variants in our cSLE cohort, including two genes implicated in mitochondrial protein degradation (<i>AFG3L2, SPG7</i>) and several genes in the interferon pathway (<i>IFIH1, IFNGR1</i>). We found that higher PRS scores were associated with increased nephritis odds (p=0.0092) but not age of onset (p>0.05). Burden testing using the optimal sequence kernel association test (SKAT-O) revealed nominal enrichment of rare variants (MAF≤ 5%) in immune-related genes, including <i>ISG15, PSMB9</i> and <i>RNASEH2A</i>, several of which are involved in type I interferon and antigen presentation pathways.</p><p><strong>Conclusion: </strong>These results have the potential to enhance our understanding of cSLE. Further studies must be conducted to expand our findings.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308632","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":"Belimumab as a possible treatment for SLE-associated pulmonary arterial hypertension: the experience from a single centre.","authors":"Qianwen Wu, Zhangdi Zhou, Huangshu Ye, Miaojia Zhang, Xiaoxuan Sun, Qiang Wang","doi":"10.1136/lupus-2026-001960","DOIUrl":"10.1136/lupus-2026-001960","url":null,"abstract":"<p><strong>Objective: </strong>To explore clinical outcomes associated with belimumab use in patients with SLE-associated pulmonary arterial hypertension (SLE-PAH).</p><p><strong>Methods: </strong>We performed an ambispective cohort study of 10 patients with SLE-PAH treated with intravenous belimumab (10 mg/kg) from January 2022 to January 2025 and compared them with 30 matched SLE-PAH controls receiving conventional immunosuppression without biologics. Patients were followed for 12 months by the same medical team. Clinical, laboratory, echocardiographic parameters, SLE Disease Activity Index 2000 and PAH risk stratification were compared between groups.</p><p><strong>Results: </strong>All patients were matched according to baseline age, sex, WHO functional class (WHO-FC), PAH treatment strategy and background SLE therapy. All enrolled patients received either dual or triple combination targeted therapy for PAH. In the SLE-PAH group treated with belimumab, rapid and sustained improvements were observed in multiple parameters, including N-terminal pro-B-type natriuretic peptide, WHO-FC, 6-minute walking distance, soluble suppression of tumorigenicity 2 levels, the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) and right ventricular end-diastolic basal dimension (RVDd). Compared with the matched control group, belimumab-treated patients showed greater improvement in TAPSE/PASP and RVDd at the 12-month follow-up, with statistically significant differences between groups. Additionally, at the 12-month follow-up, all patients in the belimumab group were stratified into the low-risk category, whereas one patient remained in the intermediate-low risk and four patients were categorised as intermediate-high risk in the matched group.</p><p><strong>Conclusion: </strong>Belimumab combined with standard PAH-targeted therapy was associated with improvements in right ventricular structure and function in patients with SLE-PAH compared with conventional immunosuppression. Further large-scale, prospective investigations are warranted to confirm these findings.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278094","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":"Phase Ib, multicentre, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneously administered mosunetuzumab in participants with systemic lupus erythematosus.","authors":"Elsa Martins, Vishala L Chindalore, X Rebecca Sheng, Aaron V Schroeder, Vivian Chen, Hardik Mody, Audrey Arjomandi, Huiyan Ashley Mao, Imran Hassan, Iwona Dankiewicz-Fares, Svetlana Agachi, Theodore A Omachi, Jay P Garg, William F Pendergraft","doi":"10.1136/lupus-2026-002019","DOIUrl":"10.1136/lupus-2026-002019","url":null,"abstract":"<p><strong>Objective: </strong>To determine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of subcutaneously administered mosunetuzumab, a CD20xCD3 T-cell-engaging bispecific antibody, in participants with systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>This phase Ib, multicentre, open-label, dose-escalation study enrolled 15 participants diagnosed with active autoantibody-positive SLE, demonstrated by an SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥4 at screening. The study included two fixed-dosing dose-finding cohorts (1.6 mg or 5 mg of mosunetuzumab on day 1) and three step-up dose-escalation cohorts (day 1 dose of mosunetuzumab established by dose finding, followed by 15 mg, 45 mg or 60 mg of mosunetuzumab on day 8). The primary objective was evaluation of safety; other key objectives were evaluating the PK and PD of mosunetuzumab. Peripheral B-cell counts and T-cell phenotyping were performed using flow cytometry.</p><p><strong>Results: </strong>Fifteen participants were enrolled from January 2022 through December 2023. Two participants discontinued treatment due to treatment-emergent adverse events (AEs). No immune effector cell-associated neurotoxicity syndrome events or high-grade cytokine release syndrome events were reported. The frequency of grade ≥3 AEs and serious AEs was 13.3% and 6.7%, respectively. Mosunetuzumab depleted peripheral B cells below the lower limit of quantification (0.441 cells/µL) in a dose-dependent manner. CD4+ and CD8+ T-cell activation occurred across all tested doses. SLEDAI-2K scores improved, especially among participants with higher baseline SLEDAI-2K scores and those receiving higher doses. The PK profile of mosunetuzumab was consistent with that observed in the relapsed or refractory follicular lymphoma population.</p><p><strong>Conclusions: </strong>Mosunetuzumab demonstrated dose-dependent peripheral B-cell depletion and a safety profile consistent with prior studies in follicular lymphoma. Based on these data, mosunetuzumab is currently being evaluated in a phase II study in severe SLE (NCT07598396).</p><p><strong>Trial registration number: </strong>NCT05155345.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272346","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":"Belimumab induces early and sustained resolution of lupus thrombocytopenia.","authors":"Nicolai Leuchten, Ioannis Parodis, Ralph Brinks, Martin Aringer","doi":"10.1136/lupus-2026-002010","DOIUrl":"10.1136/lupus-2026-002010","url":null,"abstract":"<p><strong>Objective: </strong>Belimumab has well-established efficacy in improving overall SLE disease activity and preventing flares and organ damage. Belimumab effects have been demonstrated across organ domains but have not been reported in detail for haematological manifestations. We investigated the efficacy of belimumab in thrombocytopenia and leucopenia in patients with SLE.</p><p><strong>Methods: </strong>Anonymised data on haematological parameters from five phase III randomised controlled clinical trials of belimumab were provided by GSK. These datasets included 1769 patients treated with belimumab and 1144 patients who received placebo, on top of standard therapy. We selected patients with active thrombocytopenia or leucopenia at baseline and compared sustained resolution of symptoms from the time of resolution through week 52 by means of log-rank tests.</p><p><strong>Results: </strong>At baseline, thrombocytopenia and leucopenia were present in 39 and 346 belimumab-treated patients and 25 and 203 placebo recipients, respectively. Thrombocytopenia resolved earlier with belimumab versus placebo, starting from week 2 on therapy and in a higher proportion of belimumab-treated patients (p=0.0267). One-third (13/39) of belimumab-treated and 8% (2/25) of placebo-receiving patients reached persistent resolution. In contrast to thrombocytopenia, observed improvements in leucopenia were slower, with no apparent difference between belimumab and placebo.</p><p><strong>Conclusion: </strong>This post hoc analysis of data from five large phase III RCTs suggests a benefit from belimumab compared with placebo in the haematological domain. A benefit from belimumab was seen in improving thrombocytopenia, but not leucopenia. While mild leucopenia is rarely clinically relevant, the data on thrombocytopenia will inform differential therapeutic decisions in patients with active SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272348","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":"Mental health monitoring in adolescents with SLE: associations with lupus low disease activity state and remission.","authors":"Chayanit Kongsuk, Navaporn Tangkittiwet, Sirirat Charuvanij, Yanarin Thunsiribuddhichai, Anirut Pattaragarn, Nuntawan Piyaphanee","doi":"10.1136/lupus-2026-002034","DOIUrl":"10.1136/lupus-2026-002034","url":null,"abstract":"<p><strong>Objective: </strong>Psychological comorbidities are common in adolescents with SLE. Incorporating structured mental-health screening into adolescent SLE care may facilitate improved disease control and holistic well-being. We aimed to evaluate evidence describing changes in mental health including psychological comorbidities and associations with disease states in adolescents with SLE.</p><p><strong>Methods: </strong>A prospective cohort study was conducted in adolescents aged 12-18 years diagnosed with SLE and completed paired assessments at two visits 6-12 months apart. Mental-health measures included the Patient Health Questionnaire-Adolescents (PHQ-A) (depressive symptoms), Generalised Anxiety Disorder (GAD-7) (anxiety), PedsQL Multidimensional Fatigue Scale (PedsQL-MFS) (fatigue), Pittsburgh Sleep Quality Index (PSQI) (sleep quality), Brief Illness Perception Questionnaire (B-IPQ) (illness perception) and visual analogue scale for pain (VAS-P) (pain). Disease states comprised SLE Disease Activity Index 2000 (SLEDAI-2K) (disease activity) and attainment of childhood lupus low disease activity state (cLLDAS) or childhood-onset SLE (cSLE) remission. Group comparisons, paired analyses and correlation analyses were performed.</p><p><strong>Results: </strong>120 participants were enrolled, of which 117 had complete paired assessments. Most participants were females (90.5%), with a mean age of 15.1±0.2 years. Significant improvement in mental health measures was observed including PHQ-A (3 (1, 6) vs 2 (1, 5), p=0.013), GAD-7 (2 (1, 5) vs 2 (0, 4), p=0.004) and PSQI (4.6±2.8 vs 3.9±2.4, p=0.015) scores, whereas PedsQL-MFS, B-IPQ and VAS-P scores remained unchanged. SLEDAI-2K scores were low (2 (0, 4) vs 2 (0, 3)). The proportions of achieving cLLDAS (64.1% vs 72.6%, p=0.122) and cSLE remission (27.4% vs 35.9%, p=0.021) increased. The relationship between the psychological measures and SLEDAI-2K was not observed; however, active disease (SLEDAI-2K ≥5) was associated with greater fatigue (p=0.015) at the second visit. No associations were identified between the psychological measures and cLLDAS or cSLE remission, consistently in both visits.</p><p><strong>Conclusions: </strong>Mental health monitoring over 6-12 months apart revealed changes in depressive symptoms, anxiety and sleep quality during routine paediatric SLE care. The absence of associations with cLLDAS or remission underscores the importance of integrating mental health outcomes into the treat-to-target strategies.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272377","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":"Roxadustat in lupus nephritis: a novel therapeutic signal for multifactorial anaemia.","authors":"Mario Martín-Portugués, Victor Moreno-Torres, Pedro Durán-Del Campo, Lucía Martín-Tesillano, José Portoles, Ana Huerta","doi":"10.1136/lupus-2026-002146","DOIUrl":"10.1136/lupus-2026-002146","url":null,"abstract":"","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265296","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":"Stage-resolved mapping of RP105 (CD180)-negative B cells reveals residual plasmablast-lineage skewing in SLE: a cross-sectional study.","authors":"Ayana Kanagawa, Akihito Maruyama, Tatsuki Shibuta, Mitsuteru Akahoshi, Sachiko Soejima, Yoshifumi Tada, Syuichi Koarada","doi":"10.1136/lupus-2026-001996","DOIUrl":"10.1136/lupus-2026-001996","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether clinically inactive/low-activity SLE reflects immunological remission in this cross-sectional study using CD180 (RP105)-anchored, stage-resolved profiling of peripheral B-cell differentiation.</p><p><strong>Methods: </strong>CD19⁺ B cells were analysed by flow cytometry in healthy controls (HCs; n=27), active SLE (n=29; sampled on admission before treatment initiation/escalation) and inactive/low-activity SLE (n=14; biological-free; ≥5 years of sustained Lupus Low Disease Activity State and/or Definition of Remission in SLE remission). Six ordered stages (subsets 0-5) were defined along the CD180-loss trajectory. CXCR5, CD11c, B-cell activating factor receptor and B-cell maturation antigen (BCMA) were quantified. Non-parametric tests with Benjamini-Hochberg false discovery rate (FDR) adjustment were applied.</p><p><strong>Results: </strong>Active SLE redistributed towards downstream CD180^- plasmablast-lineage stages (subsets 2-5) (14.07% vs 1.92% in HCs). Inactive/low-activity SLE retained a residual plasmablast-lineage (subset 2-5: 6.17%) expansion above HC levels despite durable quiescence. In HCs, CXCR5 positivity was high in upstream CD180⁺ compartments and declined stepwise across the trajectory. CXCR5 positivity at subset 0 was reduced in active SLE (FDR-adjusted p=0.0273) and inactive/low-activity SLE (FDR-adjusted p=0.0015) and at subset 3 in active SLE (FDR-adjusted p=0.0273) versus HCs. CD11c was enriched in upstream compartments during active disease, whereas BCMA was increased in mature downstream CD180^- stages.</p><p><strong>Conclusions: </strong>CD180-anchored, stage-resolved profiling indicates that clinical quiescence may not fully equate to immunological normalisation in SLE. These cross-sectional observations do not establish durable persistence, and longitudinal validation is needed. An upstream CXCR5 decrement detectable even in long-term quiescence is consistent with extrafollicular-leaning priming changes arising before CD180 loss; however, any implications for longitudinal immunomonitoring remain hypothesis-generating.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265241","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":"Systemic Lupus International Collaborating Clinics Frailty Index predicts mortality in systemic lupus erythematosus patients: data from the Almenara Lupus Cohort.","authors":"Benny Harold Rashuamán-Conche, Rocio Violeta Gamboa-Cárdenas, Victor Román Pimentel-Quiroz, Anubhav Singh, Cristina Reátegui-Sokolova, Claudia Elera-Fitzcarrald, Samira Garcia-Hirsh, Cesar Pastor-Asurza, Zoila Rodríguez-Bellido, Risto Alfredo Perich-Campos, Graciela S Alarcón, Manuel Francisco Ugarte-Gil","doi":"10.1136/lupus-2025-001938","DOIUrl":"10.1136/lupus-2025-001938","url":null,"abstract":"<p><strong>Objective: </strong>Frailty has been shown to predict damage accrual in patients with systemic lupus erythematosus (SLE), including those from Latin America. However, the impact of frailty on mortality has been scarcely evaluated, particularly in Latin American populations. The aim of this study was to evaluate frailty as a predictor of mortality in Latin American SLE patients.</p><p><strong>Methods: </strong>Patients from a single-centre 2012-2025 prevalent cohort were studied. Mortality was defined as the vital status according to the Peruvian Department of Health. Frailty was ascertained using the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) as a continuous variable. Univariable and multivariable Cox regression models were done to estimate its impact on mortality. Multivariable models were adjusted for possible confounders. Sensitivity analyses were performed including data up to March 2020 to avoid the potential influence of the COVID-19 pandemic. Additionally, a Kaplan-Meier curve was calculated by frail status (frail, SLICC-FI >0.21; non-frail, SLICC-FI ≤0.21).</p><p><strong>Results: </strong>Four hundred and ninety-five patients were included, 456 (92.1%) were women and 96 (19.4%) were frail. Their mean (SD) age at diagnosis was 35.0 (14.0) years, their mean disease duration at baseline was 6.7 (6.1) years and their mean follow-up time was 8.5 (4.2) years. Fifty-six (11.3%) patients died during the follow-up. The SLICC-FI predicted mortality even after adjusting for possible confounders (hazard ratio (HR)=1.54 (CI 95% 1.11 to 2.14), p=0.010). This prediction capability remained on the sensitivity analyses (HR 1.85; (95% CI 1.30 to 2.61), p<0.001).</p><p><strong>Conclusion: </strong>Frailty, as ascertained with the SLICC-FI, was a predictor of mortality in a Latin American cohort of SLE patients. Frailty could be considered in the monitoring of SLE patients; possible interventions to modify it should be developed.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239587","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}