Arthritis & Rheumatology最新文献

{"title":"Plasma Proteome Reflects Tissue Damage and Clinical Manifestations in Patients With Inflammatory Myopathies.","authors":"Yue-Bei Luo, Josefin Kenrick, Angeles S Galindo-Feria, Antonella Notarnicola, Ana Daniela Ulloa Navas, Irene Peralta-Garcia, Orane Demuynck, Andrea Kemp, Valérie Leclair, Karin Lodin, Eveline Van Gompel, Lara Dani, Fabricio Espinosa-Ortega, Maryam Dastmalchi, Leonid Padyukov, Charlotta Preger, María Bueno Álvez, Mathias Uhlén, Peter Nilsson, Fredrik Edfors, Lina-Marcela Diaz-Gallo, Elisa Pin, Ingrid E Lundberg, Begum Horuluoglu","doi":"10.1002/art.70311","DOIUrl":"10.1002/art.70311","url":null,"abstract":"<p><strong>Objective: </strong>Tissue-specific biomarkers that are reliable and associated with clinical manifestations of idiopathic inflammatory myopathy (IIM) are lacking. The blood circulation in individuals serves as a central conduit, allowing communication between tissues and facilitating clearance and recycling of tissue-derived proteins. Thus, we applied a dual antibody-based proximity extension assay to profile >1,000 proteins in subtypes of patients with IIM.</p><p><strong>Methods: </strong>Plasma samples from 201 patients diagnosed with IIM at Karolinska University Hospital were analyzed using Olink Proximity Extension Assay technology. Clinical manifestations, disease activity measurements, and laboratory test results were collected. First, we evaluated differential protein abundance across IIM subtypes. Then we calculated tissue scores for each disease subtype using tissue gene expression databases. Finally, interferon (IFN) pathway scores were calculated.</p><p><strong>Results: </strong>Plasma from patients with dermatomyositis was enriched for IFN signaling and skin-associated proteins, antisynthetase syndrome (ASyS) for lung-associated proteins, immune-mediated necrotizing myopathy (IMNM) for muscle-associated proteins, and inclusion body myositis for T cell-response proteins. Patients with IMNM showed the highest tissue score for skeletal muscles, and patients with ASyS showed the highest lung tissue scores. Skeletal muscle scores correlated strongly with muscle disease activity visual analog scale scores, creatine kinase levels, and muscle weakness score. Patients with interstitial lung disease along with anti-MDA5 and those with anti-Jo1 autoantibodies showed differential enrichment of surfactant proteins and IFN pathway activation.</p><p><strong>Conclusion: </strong>Circulatory proteome is a promising tool to capture distinct tissue-specific responses that correlate with disease activity and tissue injury in patients with IIM.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of the Bispecific Anti-BAFF/IL-21 Antibody CZ105 Bis2 in Models of Systemic Lupus Erythematosus.","authors":"Xiwei Feng, Di Long, Huiqi Yin, Liming Li, Zijun Wang, Junpeng Zhao, Xinyu Fan, Wei Wu, Haijing Wu, Qianjin Lu","doi":"10.1002/art.70310","DOIUrl":"10.1002/art.70310","url":null,"abstract":"<p><strong>Objective: </strong>Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease in which B cells play a crucial role. Although belimumab, the first B cell-targeted biologic approved for SLE, has demonstrated efficacy and tolerability, approximately 30%-40% of patients show suboptimal responses. Interleukin-21 (IL-21), a key regulator of B cell differentiation and function, is closely associated with SLE disease activity, but IL-21-targeted monotherapy has shown limited clinical efficacy. This study aimed to develop and characterize a bispecific antibody targeting both IL-21 and B cell-activating factor (BAFF) and to determine whether dual blockade provides greater therapeutic efficacy than inhibition of either pathway alone.</p><p><strong>Methods: </strong>We prepared humanized 18B10 (h18B10), an anti-IL-21 monoclonal antibody. Building on this candidate, we constructed CZ105 Bis2, a bispecific antibody assembled by fusing the variable domains of h18B10 and belimumab, enabling concurrent blockade of IL-21 and BAFF signaling pathways.</p><p><strong>Results: </strong>In vitro functional assays verified that CZ105 Bis2 exhibits binding affinity and cytokine neutralization potency equivalent or superior to its two parent molecules. Compared with selective inhibitors of BAFF or IL-21, CZ105 Bis2 elicited more robust suppression of in vivo B cell effector functions. In the keyhole limpet hemocyanin model, CZ105 Bis2 significantly reduced T cell-dependent, antigen-specific B cell responses. In both pristane-induced lupus mouse models and humanized lupus-like models (chronic graft-vs-host disease), CZ105 Bis2 decreased anti-double-stranded DNA antibody levels, reduced proteinuria, and alleviated renal inflammatory infiltration.</p><p><strong>Conclusion: </strong>Our preclinical data confirm that CZ105 Bis2 achieves superior efficacy over single-target biologics across in vitro and in vivo systems, supporting its translational potential to improve clinical outcomes in SLE.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multifaceted Interplay Among Hemophagocytosis, Interleukin-18, and Type I Interferon Distinguishes Still Disease From Other Autoinflammatory Diseases","authors":"Yvonne M. Mueller PhD,&nbsp;Charlotte Girard MD, PhD,&nbsp;Harmen J. G. van de Werken PhD,&nbsp;Stefan J. Erkeland PhD,&nbsp;Dwin G. B. Grashof MSc,&nbsp;Laurie Vaillant PhD,&nbsp;Renske J. H. den Dekker MSc,&nbsp;Iris van Zuijen MSc,&nbsp;Sharon Veenbergen PhD,&nbsp;Fanny Coffin PhD,&nbsp;Eric Bindels PhD,&nbsp;Yvan Jamilloux MD,&nbsp;Katerina Laskari MD,&nbsp;Vassili Soumelis MD, PhD,&nbsp;Bruno Fautrel MD, PhD,&nbsp;Cem Gabay MD, PhD,&nbsp;Peter D. Katsikis MD, PhD","doi":"10.1002/art.70102","DOIUrl":"10.1002/art.70102","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The unknown pathophysiology and the lack of specific features for systemic juvenile idiopathic arthritis and adult-onset Still disease (collectively known as Still disease; SD) delay diagnosis and appropriate treatment. The goal of this study was to identify features and mechanisms that distinguish SD from other systemic autoinflammatory diseases (SAID).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the SomaScan assay and RNA sequencing (RNA-Seq), we determined the plasma proteomes and immune cell microRNA (miRNA) and RNA transcriptomes of 372 patients with SAID, respectively. Proteomic findings were validated by enzyme-linked immunosorbent assays. SD (n = 72) and non-SD SAIDs (n = 300) were compared to identify distinguishing features of SD. We performed integrated and unbiased analyses of all data sets using weighted gene correlation network analysis to identify feature modules that characterize SD and stratify patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated plasma heme oxygenase 1 (HO-1) and interleukin-18 (IL-18) strongly correlate and characterize SD but do not associate with general inflammation. SD was characterized by ferroptosis in plasma, type I interferon (IFN) signaling in monocyte transcriptomes, and elevated natural killer cell miRNA-146a-5p, which is an IL-18 induced miRNA. Finally, we identified feature modules that distinguish SD from other SAIDs and stratified patients with SD into two distinct subgroups not attributable to disease activity or inflammation but hemophagocytosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This unprecedented large omics data set of SAIDs revealed that complex interactions among hemophagocytosis, IL-18, and type I IFN signaling characterize SD. Furthermore, two distinct subgroups in patients with SD were distinguished by the degree of hemophagocytic activity. Finally, the large proteomics and RNA-Seq data sets generated in this study can serve as an invaluable resource for the further investigation of SD and other SAIDs.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1961-1974"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Interleukin-10 Levels as a Predictive Biomarker for Achieving Clinical Response With Abatacept in Patients Who Were Disease-Modifying Antirheumatic Drug Naive and Anti–Citrullinated Protein Antibody Positive With Early Rheumatoid Arthritis","authors":"Jinqi Liu PhD,&nbsp;Yicong Li PhD,&nbsp;Kai Fu PhD,&nbsp;Chun Wu PhD,&nbsp;Peter Schafer PhD,&nbsp;Sean E. Connolly PhD,&nbsp;Ian M. Catlett PhD,&nbsp;Michael A. Maldonado MD,&nbsp;Robert Wong MD,&nbsp;Paul Emery FMedSci,&nbsp;Yoshiya Tanaka MD,&nbsp;Vivian P. Bykerk MD,&nbsp;Clifton O. Bingham MD,&nbsp;Thomas W. J. Huizinga MD, PhD,&nbsp;Roy Fleischmann MD","doi":"10.1002/art.70106","DOIUrl":"10.1002/art.70106","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Predictive biomarkers for patients with early rheumatoid arthritis (RA) are needed. This exploratory post hoc analysis investigated inflammatory biomarkers associated with baseline disease activity and biomarkers predictive of treatment response in patients who were seropositive with early RA from a phase 3 study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The AVERT-2 study (NCT02504268) included patients who were disease-modifying antirheumatic drug naive and anti–citrullinated protein antibody positive randomized to abatacept and methotrexate (MTX) or placebo and MTX for 56 weeks. Correlations were assessed among biomarkers and disease activity, pharmacodynamic (PD) changes on disease-associated biomarkers in response to treatment, and baseline biomarkers to predict treatment response at week 52.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the analysis, 446 patients received abatacept and MTX and 300 received placebo and MTX. Of 103 biomarkers, 47 demonstrated a significant reduction in PD changes with abatacept and MTX versus placebo and MTX, with 18 out of 47 biomarkers showing correlations with baseline disease activity. High baseline interleukin-10 (IL-10) levels were associated with greater probability of achieving efficacy measures by week 52 in patients receiving abatacept and MTX versus placebo and MTX, consistent with a significant reduction in disease activity with abatacept and MTX (<i>P</i> &lt; 0.03 to <i>P</i> &lt; 0.0007). Higher baseline IL-10 levels were associated with lower bone erosive development with abatacept and MTX compared with placebo and MTX.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Treatment with abatacept and MTX resulted in significantly greater reduction of biomarkers relevant to RA, and high baseline IL-10 levels predicted better treatment response with abatacept and MTX versus placebo and MTX across clinical outcomes. Findings suggest a well-suited mechanism of action for abatacept and MTX in patients with early RA and high baseline IL-10 levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1826-1836"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T Cells in Osteoarthritis: Drivers, Repairers, or Bystanders in Osteoarthritis?","authors":"Tonia L. Vincent MD, PhD,&nbsp;Andrew P. Cope MD, PhD","doi":"10.1002/art.70135","DOIUrl":"10.1002/art.70135","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1813-1815"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential Role of Synovial T Cell Infiltration Following Knee Joint Injury in Symptoms and Progression to Osteoarthritis","authors":"Babak Moradi MD,&nbsp;Miriam T. Jackson PhD,&nbsp;Cindy C. Shu PhD,&nbsp;Susan M. Smith BSc,&nbsp;Margaret M. Smith PhD,&nbsp;Sanaa Zaki BVSc, PhD,&nbsp;Hadrian Platzer MD,&nbsp;Nils Rosshirt MD,&nbsp;David Giangreco MD,&nbsp;Carla R. Scanzello MD, PhD,&nbsp;Christopher B. Little BVMS, PhD","doi":"10.1002/art.70157","DOIUrl":"10.1002/art.70157","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Identification of osteoarthritis (OA)–specific synovial inflammatory pathways and their temporal relevance is critical for therapeutic targeting. We compared mononuclear inflammatory/immune cell responses following joint injury that does or does not lead to OA to define bona fide OA-associated cellular events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We undertook detailed temporal flow cytometric and messenger RNA (mRNA) expression analysis in mice after sham or destabilization of the medial meniscus (DMM) surgery. This was compared with patients with meniscal injury and OA, evaluating the role of synovial monocytes/macrophages versus lymphocytes in catabolic metalloproteinase secretion in vitro. We determined the effect of transient or delayed systemic T cell depletion on DMM-induced OA pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>OA-inducing/DMM and non–OA-inducing/sham surgery had an identical synovial monocyte/macrophage number, activation, and polarization. The number and activation of synovial (not splenic or peripheral blood) CD4⁺ and CD8⁺ lymphocytes were increased from one day after DMM versus sham and showed a persistent cyclical elevation throughout OA onset and progression. There was a temporal imbalance in synovial Th17/Treg and Th1/Th2 lymphocytes during DMM-induced OA initiation and progression. We confirmed early postinjury and late OA CD3/CD8 T cell responses in synovial tissues from patients, identified an association between CD8 and early postinjury symptoms, and defined a significant role for CD3⁺ T cells in synovial metalloproteinase secretion. Anti-CD3 cell depletion studies in mice provided an initial approach to testing this hypothesis, offering preliminary evidence that early postinjury T cell responses may be associated with long-term OA pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We identify a hitherto unappreciated pathophysiologic role of acute T cell activation after joint injury in long-term posttraumatic OA risk, providing a novel diagnostic and therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1863-1877"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147631959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic Variants in Immune Dysregulation: An Ongoing Challenge","authors":"Sofia Torreggiani MD,&nbsp;Ivona Aksentijevich MD","doi":"10.1002/art.70179","DOIUrl":"10.1002/art.70179","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1816-1818"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Detection of Myositis-Specific Autoantibodies Using Luciferase Immunoprecipitation Systems Assay: Comparison With Line Blot and Conventional Immunoprecipitation","authors":"Peter D. Burbelo PhD,&nbsp;Iago Pinal-Fernandez MD, PhD,&nbsp;Maria Casal-Dominguez MD, PhD,&nbsp;Xin Tian PhD,&nbsp;Shijinqiu Gao MS,&nbsp;Neha Gupta BS,&nbsp;Eric W. Robbins MD,&nbsp;John A. Chiorini PhD,&nbsp;Christopher A. Mecoli MD, MHS,&nbsp;Lisa Christopher-Stine MD, MPH,&nbsp;Livia Casciola-Rosen PhD,&nbsp;Andrew L. Mammen MD, PhD,&nbsp;Sonye K. Danoff MD, PhD,&nbsp;Anthony F. Suffredini MD,&nbsp;Julio A. Huapaya MD, MHS","doi":"10.1002/art.70103","DOIUrl":"10.1002/art.70103","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Myositis-specific autoantibodies guide the diagnosis and classification of idiopathic inflammatory myopathies, but current immunoassays vary in accuracy, particularly for autoantibodies associated with interstitial lung disease. To compare the performance of the luciferase immunoprecipitation systems (LIPS) assay with line blot and immunoprecipitation (IP) and to evaluate whether antibody-specific thresholds modify line blot concordance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed 279 sera with line blot results from the Johns Hopkins Myositis Center. LIPS was performed for anti–Jo-1, anti–PL-7, anti–PL-12, anti–MDA-5, anti-EJ, and anti-Ro52 autoantibodies. Line blot results were evaluated using standard thresholds (≥36 and ≥71 arbitrary units [AU]). Assay performance was evaluated against IP (n = 141). In patients without IP (n = 138), clinical diagnoses were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LIPS showed excellent agreement with IP (κ = 0.90, area under the receiver operating characteristic curve 0.935), outperforming line blot. Line blot cutoffs influenced performance: ≥36 AU increased sensitivity (92.9%) but reduced specificity (73.8%), whereas ≥71 AU improved specificity (92.9%) but lowered sensitivity (82.8%). Antibody-specific thresholds modified concordance but remained quantitatively inferior to LIPS. In patients without IP, concordance between LIPS and line blot was 89% at ≥36 AU and 83% at ≥71 AU. LIPS-positive cases were enriched for antisynthetase syndrome and dermatomyositis. Among discordant cases (line blot positive and LIPS negative), most were clinically classified as inclusion body myositis (5 of 11). For anti-Ro52, discrepancies were most frequent at titers &lt;36 AU.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>LIPS provides quantitative discrimination, strong concordance with IP, and improved performance compared with line blot, particularly at low to intermediate titers. By reducing misclassification and complementing antibody-specific thresholds, LIPS has the potential to enhance clinical stratification in patients with myositis.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1952-1960"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Level Characterization of B Cell Depletion and Repopulation Following Rituximab in Systemic Lupus Erythematosus","authors":"Haerin Jang MSc,&nbsp;Norzawani Buang PhD,&nbsp;Catherine Sutherland PhD,&nbsp;Wanseon Lee PhD,&nbsp;Lauren Overend DPhil,&nbsp;Tarran S. Rupall MSc,&nbsp;Katie L. Burnham DPhil,&nbsp;Matthew C. Pickering MD, PhD,&nbsp;Marina Botto MD,&nbsp;Emma E. Davenport DPhil","doi":"10.1002/art.70116","DOIUrl":"10.1002/art.70116","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Rituximab, a CD20⁺ B cell depletion therapy, is frequently used to treat systemic lupus erythematosus (SLE). However, variability in patient response highlights the need for a deeper understanding of the underlying immune cell dynamics of B cell depletion and repopulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted longitudinal single-cell profiling of nine patients with SLE treated with rituximab from pretreatment to up to 15 months post-treatment. These were compared with eight healthy controls. We profiled 169,513 immune cells via single-cell RNA, surface protein, B cell receptor (BCR), and T cell receptor sequencing, and bulk BCR repertoire sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant depletion of naïve, memory, and age-associated B cells was observed early post-treatment, followed by later repopulation of mainly transitional B cells. A fraction of antigen-experienced B cells, particularly in nonresponders, persisted through the depletion. BCR repertoire analysis revealed reduced diversity and persistent clones in antigen-experienced cells at early post-treatment, but these effects were not long-lasting. Repopulated naïve B cells in rituximab responders exhibited reduced NF-κB pathway activation, aligning with lower B cell activating factor receptor (BAFF-R) surface protein levels. In non-B cells, we identified 27 differentially expressed genes across seven immune cell subtypes post-rituximab, with regulatory CD4 T cells and double negative (DN) T cells showing the most changes. Responders specifically had increased expression of genes related to cytotoxicity, major histocompatibility complex class II antigen presentation, and T cell activation in CD4 T central memory and DN T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our longitudinal profiling provides single-cell resolution of the shifts in immune cell dynamics following B cell depletion.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1907-1919"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147363487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Blood Proteins Reveal What Transcripts Miss: Immune Cell Priming and the Road to Prognostic Biomarkers in Lupus","authors":"Ioannis Parodis MD, PhD","doi":"10.1002/art.70065","DOIUrl":"10.1002/art.70065","url":null,"abstract":"<p>Dr Parodis contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr Parodis confirms that he has provided the final approval of the version to be published and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 9","pages":"1823-1825"},"PeriodicalIF":9.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}