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Glomerular CD68+ macrophages infiltration at initial biopsy predicts response to standard immunosuppression in proliferative lupus nephritis
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103392
Cailing Su , Ansheng Cong , Heng Wu , Zhanmei Zhou , Zuoyu Hu , Jiao Luo , Shuang Cui , Dongyan Xu , Zhuoyu Zhou , Zhijie Huang , Manqiu Yang , Guobao Wang , Wei Cao
{"title":"Glomerular CD68+ macrophages infiltration at initial biopsy predicts response to standard immunosuppression in proliferative lupus nephritis","authors":"Cailing Su ,&nbsp;Ansheng Cong ,&nbsp;Heng Wu ,&nbsp;Zhanmei Zhou ,&nbsp;Zuoyu Hu ,&nbsp;Jiao Luo ,&nbsp;Shuang Cui ,&nbsp;Dongyan Xu ,&nbsp;Zhuoyu Zhou ,&nbsp;Zhijie Huang ,&nbsp;Manqiu Yang ,&nbsp;Guobao Wang ,&nbsp;Wei Cao","doi":"10.1016/j.jaut.2025.103392","DOIUrl":"10.1016/j.jaut.2025.103392","url":null,"abstract":"<div><h3>Objective</h3><div>Predictive models of kidney response to standard immunosuppression are needed in proliferative lupus nephritis (LN). We tested the kidney macrophage infiltration at initial biopsy.</div></div><div><h3>Methods</h3><div>The prospective study was performed in 247 patients with newly diagnosed proliferative LN in 2 independent cohorts. Infiltrates of macrophages and lymphocytes in initial biopsies were identified using single-cell RNA sequencing and immunostaining analysis. The outcome was kidney response to standard immunosuppression at 1 year, defined clinically and histologically. Kidney infiltrates were investigated for association with kidney response. Models that combined kidney infiltrates and clinical parameters for predicting kidney response were developed and validated using machine learning algorithms.</div></div><div><h3>Results</h3><div>In Derivation cohort, glomerular infiltration of CD68<sup>+</sup> macrophages at initial biopsy was associated with 1-year clinical response. Subjects in the highest tertile of glomerular CD68<sup>+</sup> macrophage infiltrate (<em>versus</em> the lowest) had a 7.92-fold increase in probability of clinical response. An intelligent model incorporating infiltration score of glomerular CD68<sup>+</sup> macrophage into clinical measures (area under the curve [AUC] 0.82) outperformed traditional clinical measure-based model (AUC 0.76) in predicting clinical response (P = 0.01). This intelligent model performed well in an independent Validation cohort. Furthermore, in 10 patients undergoing repeat kidney biopsy after 1 year of standard immunosuppression, our intelligent model effectively predicted histological response.</div></div><div><h3>Conclusion</h3><div>Intensity of glomerular CD68<sup>+</sup> macrophage infiltration at initial biopsy predicted 1-year kidney response to standard therapy in proliferative LN. The intelligent model, which combines glomerular CD68<sup>+</sup> macrophage infiltrates with clinical data at biopsy, could help discriminate responders from non-responders, enabling personalized therapy.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103392"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519104","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}
引用次数: 0
Autoantibodies against α-synuclein inhibit its aggregation and cytotoxicity
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103390
Carmen Noelker , Florian Seitz , Annekathrin Sturn , Frauke Neff , Luminita-Cornelia Andrei-Selmer , Lorenz Rau , Armin Geyer , J. Alexander Ross , Michael Bacher , Richard Dodel
{"title":"Autoantibodies against α-synuclein inhibit its aggregation and cytotoxicity","authors":"Carmen Noelker ,&nbsp;Florian Seitz ,&nbsp;Annekathrin Sturn ,&nbsp;Frauke Neff ,&nbsp;Luminita-Cornelia Andrei-Selmer ,&nbsp;Lorenz Rau ,&nbsp;Armin Geyer ,&nbsp;J. Alexander Ross ,&nbsp;Michael Bacher ,&nbsp;Richard Dodel","doi":"10.1016/j.jaut.2025.103390","DOIUrl":"10.1016/j.jaut.2025.103390","url":null,"abstract":"<div><div>Aggregates of α-synuclein (α-Syn) are the major component of the Lewy bodies associated with Parkinson's disease. Recently, naturally occurring autoantibodies against α-synuclein (α-Syn-nAbs) were detected. Herein we have isolated and further characterized such α-Syn-nAbs. Using an affinity column coated with α-Syn, we have isolated α-Syn-nAbs from a commercially available intravenous Immunoglobulin (IVIg) preparation. A methodological approach based on ELISA, Western blotting and immunoprecipitation as well as surface plasmon resonance, was used to determine binding capacity to α-Syn. The epitope was determined via peptide array membrane and the functionality was tested <em>in vitro</em> using a toxicity and a fibrillation assay. The autoantibodies display strong binding capacity to α-Syn as demonstrated by ELISA, immunoprecipitation and Western blotting analysis. The binding affinities of the purified autoantibodies were analyzed in detail by surface plasmon resonance (Biacore). The epitope on α-Syn that is recognized by the α-Syn nAbs was fully determined. A sequence within the non-amyloid component (NAC)-Region of α-Syn is crucial for the binding of α-Syn-nAbs to α-Syn. Furthermore, the α-Syn-nAbs had an inhibitory effect on α-Syn fibril formation and were also able to specifically reverse the toxicity of α-Syn oligomers species in human neuroblastoma (SH-SY5Y) cells. Our results emphasize the possible importance of naturally occurring autoantibodies for the pathogenesis of Parkinson's disease. Since autoantibodies against α-Syn are detectable in human serum and cerebrospinal fluid and interfere with pathological events associated with α-Syn, they may provide a candidate for the treatment of Parkinson's disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103390"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535014","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}
引用次数: 0
Sex differences in biomarkers and biologic mechanisms in psoriatic diseases and spondyloarthritis 银屑病和脊柱关节炎生物标志物和生物机制的性别差异
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103394
Steven Dang , Joan Wither , Igor Jurisica , Vinod Chandran , Lihi Eder
{"title":"Sex differences in biomarkers and biologic mechanisms in psoriatic diseases and spondyloarthritis","authors":"Steven Dang ,&nbsp;Joan Wither ,&nbsp;Igor Jurisica ,&nbsp;Vinod Chandran ,&nbsp;Lihi Eder","doi":"10.1016/j.jaut.2025.103394","DOIUrl":"10.1016/j.jaut.2025.103394","url":null,"abstract":"<div><div>Psoriasis and spondyloarthritis (SpA), including psoriatic arthritis (PsA), are immune-mediated inflammatory conditions that affect the skin and musculoskeletal system. Males and female patients with psoriatic disease and SpA exhibit differences in clinical presentation, disease progression, and treatment response. The underlying biological mechanisms driving these sex differences remain poorly understood. This review explores the current evidence on sex-related differences in biomarkers and biological pathways in psoriasis, PsA, and SpA. While no conclusive sex-specific biomarkers have been validated, this review highlights several sex-related differences in biomarkers and biological pathways, including differences in bone turnover markers, IL-23/IL-17 pathway activity, pro-inflammatory cytokines, and cardio-metabolic profiles that may partially contribute to the clinical differences observed between male and female patients. Sex hormones may contribute to the altered bone metabolism and immune regulation in females. To effectively identify and validate sex-specific biomarkers, there is a need to prioritize sex as a biological variable in future research. Adopting such an approach should enhance more personalized therapeutic strategies and improve management for male and female patients with psoriatic disease and SpA.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103394"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527267","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}
引用次数: 0
Total lung capacity is predictive of disease severity and survival in systemic sclerosis: A longitudinal analysis in 2347 patients from the French National Cohort Study
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103391
Benjamin Chaigne , Alexandre Bense , Frédérique Aubourg , Christian Agard , Yannick Allanore , Alice Berezne , Grégory Pugnet , Eric Hachulla , Vincent Cottin , Arnaud Hot , Bertrand Dunogue , Anuxcy Kanagaratnam , Sylvain Palat , Alain Lescoat , Sabine Berthier , Emmanuel Chatelus , Sébastien Rivière , David Launay , Marie-Elise Truchetet , Anh Tuan Dinh-Xuan , Perrine Smets
{"title":"Total lung capacity is predictive of disease severity and survival in systemic sclerosis: A longitudinal analysis in 2347 patients from the French National Cohort Study","authors":"Benjamin Chaigne ,&nbsp;Alexandre Bense ,&nbsp;Frédérique Aubourg ,&nbsp;Christian Agard ,&nbsp;Yannick Allanore ,&nbsp;Alice Berezne ,&nbsp;Grégory Pugnet ,&nbsp;Eric Hachulla ,&nbsp;Vincent Cottin ,&nbsp;Arnaud Hot ,&nbsp;Bertrand Dunogue ,&nbsp;Anuxcy Kanagaratnam ,&nbsp;Sylvain Palat ,&nbsp;Alain Lescoat ,&nbsp;Sabine Berthier ,&nbsp;Emmanuel Chatelus ,&nbsp;Sébastien Rivière ,&nbsp;David Launay ,&nbsp;Marie-Elise Truchetet ,&nbsp;Anh Tuan Dinh-Xuan ,&nbsp;Perrine Smets","doi":"10.1016/j.jaut.2025.103391","DOIUrl":"10.1016/j.jaut.2025.103391","url":null,"abstract":"<div><h3>Background</h3><div>Total lung capacity (TLC) is seldom assessed in the prediction of systemic sclerosis (SSc) disease severity.</div></div><div><h3>Objective</h3><div>To describe and analyse TLC in SSc.</div></div><div><h3>Methods</h3><div>We performed a retrospective multicentre study of SSc patients enrolled in the French national SSc cohort with at least one TLC assessment, described patients based on baseline TLC measurements, modelized TLC trajectories in SSc, and associated TLC measures with disease prognosis.</div></div><div><h3>Results</h3><div>Two thousand three hundred and forty-seven patients were included in the study. Baseline TLC was associated with disease severity and survival, as well as with the occurrence of interstitial lung disease (ILD), lung fibrosis (LF), and pulmonary arterial hypertension (PAH). Individual TLC trajectories varied among patients. Different models of TLC trajectories were assessed using latent process mixed models. The best model showed that the vast majority of SSc patients had stable TLC trajectories and clustered patients into three groups predictive of SSc survival, ILD, LF, and PAH. Lastly, a 10 % decrease of TLC was found to be predictive of a 5 % decrease in forced vital capacity (FVC), a 10 % decrease in DLCO, and consequently an earlier predictive marker of ILD and LF than FVC.</div></div><div><h3>Limitations</h3><div>Retrospective study.</div></div><div><h3>Conclusion</h3><div>TLC is predictive of disease severity and survival in SSc and SSc-ILD. This work suggests TLC as an earlier risk factor for ILD and LF than FVC in SSc.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103391"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535013","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}
引用次数: 0
Differences in innate immune cell populations distinguish autoimmune from herpesvirus-associated encephalitis
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103396
Saskia Räuber , Andreas Schulte-Mecklenbeck , Kelvin Sarink , Kristin S. Golombeck , Christina B. Schroeter , Alice Willison , Christopher Nelke , Christine Strippel , Andre Dik , Marco Gallus , Stjepana Kovac , Heinz Wiendl , Gerd Meyer zu Hörste , Tobias Ruck , Oliver M. Grauer , Udo Dannlowski , Tim Hahn , Catharina C. Gross , Sven G. Meuth , Nico Melzer
{"title":"Differences in innate immune cell populations distinguish autoimmune from herpesvirus-associated encephalitis","authors":"Saskia Räuber ,&nbsp;Andreas Schulte-Mecklenbeck ,&nbsp;Kelvin Sarink ,&nbsp;Kristin S. Golombeck ,&nbsp;Christina B. Schroeter ,&nbsp;Alice Willison ,&nbsp;Christopher Nelke ,&nbsp;Christine Strippel ,&nbsp;Andre Dik ,&nbsp;Marco Gallus ,&nbsp;Stjepana Kovac ,&nbsp;Heinz Wiendl ,&nbsp;Gerd Meyer zu Hörste ,&nbsp;Tobias Ruck ,&nbsp;Oliver M. Grauer ,&nbsp;Udo Dannlowski ,&nbsp;Tim Hahn ,&nbsp;Catharina C. Gross ,&nbsp;Sven G. Meuth ,&nbsp;Nico Melzer","doi":"10.1016/j.jaut.2025.103396","DOIUrl":"10.1016/j.jaut.2025.103396","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune encephalitis (AIE) is a disabling inflammatory condition of the brain deemed to be due to a dysregulated immune response. Viral infections and malignancies together with certain genetic polymorphisms are thought to contribute to the pathogenesis of AIE, yet the exact mechanisms remain insufficiently understood. Diagnosis of AIE currently relies on clinical consensus criteria. However, diagnostic workup can be challenging in some cases, potentially delaying treatment initiation associated with poor clinical outcomes.</div><div>This study aims to investigate the systemic and intrathecal immune cell profiles of AIE in comparison to viral meningoencephalitis (VME) as a clinically relevant differential diagnosis and evaluate its diagnostic and therapeutic potential.</div></div><div><h3>Methods</h3><div>97 mainly treatment-naïve AIE patients, 47 patients with VME, and 109 somatic symptom disorder (SD) controls were included. Analysis of peripheral blood (PB) and cerebrospinal fluid (CSF) immune cell profiles was performed using multidimensional flow cytometry (mFC) in combination with novel computational approaches.</div></div><div><h3>Results</h3><div>We were able to identify alterations in the adaptive B and T cell-mediated immune response in AIE compared to SD controls which correspond to respective changes in the brain parenchyma. AIE and VME exhibit similar patterns of adaptive B and T cell responses and differ in pattern of innate immunity especially NK cells. MFC together with routine CSF parameters can differentiate AIE from VME and SD controls implying diagnostic potential.</div></div><div><h3>Conclusion</h3><div>AIE is characterized by a B and T cell-mediated systemic and intrathecal immune-cell signature which corresponds to changes reported in the brain parenchyma providing insights into immunopathogenesis. Differences between AIE and VME were most prominent for the innate immune response indicating a potential role of NK cells in the pathogenesis of autoimmunity. Our data provides evidence that mFC could be a novel complementary approach to the diagnosis of AIE with diagnostic, therapeutic, and prognostic implications.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103396"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535015","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}
引用次数: 0
Advanced pulmonary sarcoidosis
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103397
Florence Jeny , Dominique Valeyre , Elyse E. Lower , Robert P. Baughman
{"title":"Advanced pulmonary sarcoidosis","authors":"Florence Jeny ,&nbsp;Dominique Valeyre ,&nbsp;Elyse E. Lower ,&nbsp;Robert P. Baughman","doi":"10.1016/j.jaut.2025.103397","DOIUrl":"10.1016/j.jaut.2025.103397","url":null,"abstract":"<div><div>Sarcoidosis affects the lungs in most patients. Manifestations of pulmonary sarcoidosis range from asymptomatic to death. Approximately a quarter of sarcoidosis patients develop chronic pulmonary disease. Advanced pulmonary sarcoidosis patients are those who have progressive disease and are at risk for significant morbidity and mortality. There are several features associated with advanced pulmonary disease: pulmonary fibrosis, pulmonary hypertension, chronic pulmonary inflammation, and/or complications of disease or therapy. Large retrospective studies have identified pulmonary fibrosis and pulmonary hypertension as the major causes of respiratory failure and death in pulmonary sarcoidosis. The high-resolution computer tomography scan (HRCT) and echocardiogram are key methods in screening for pulmonary hypertension and pulmonary fibrosis. Therapy for chronic pulmonary inflammation has been the major focus in chronic disease. However, treatment for pulmonary hypertension has been studied in sarcoidosis. To date, treatment studies for sarcoidosis associated progressive pulmonary fibrosis have been underpowered to demonstrate clear cut benefit of anti-fibrotic agents.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103397"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621408","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}
引用次数: 0
Poorer survival for patients with inflammatory arthritis treated with immune checkpoint inhibitors for melanoma
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103400
H.B. Tenstad , C.H. Ruhlmann , S. Möller , S. Kjaer , L. Bastholt , S.A. Just , H. Lindegaard
{"title":"Poorer survival for patients with inflammatory arthritis treated with immune checkpoint inhibitors for melanoma","authors":"H.B. Tenstad ,&nbsp;C.H. Ruhlmann ,&nbsp;S. Möller ,&nbsp;S. Kjaer ,&nbsp;L. Bastholt ,&nbsp;S.A. Just ,&nbsp;H. Lindegaard","doi":"10.1016/j.jaut.2025.103400","DOIUrl":"10.1016/j.jaut.2025.103400","url":null,"abstract":"<div><h3>Background</h3><div>Patients with inflammatory arthritis treated with immune checkpoint inhibitors (ICIs) for melanoma face unique challenges, including disease flares and reduced treatment efficacy. Evidence on the survival impact of pre-existing arthritis in this population remains limited.</div></div><div><h3>Methods</h3><div>We conducted an observational cohort study using data from two Danish national registries, DANBIO and DAMMED, including patients with melanoma and pre-existing inflammatory arthritis treated with ICIs. Cases were matched with controls without arthritis based on sex, age, melanoma subtype, disease stage, and treatment regimen. Outcomes included overall survival (OS), progression-free survival (PFS)/recurrence-free survival (RFS), changes in rheumatic disease activity, and healthcare utilization.</div></div><div><h3>Results</h3><div>Seventy-five patients with inflammatory arthritis were identified, initiating 91 ICI treatment courses. Patients with arthritis demonstrated poorer OS (HR 1.4, 95 % CI: 1.04–1.91) and PFS/RFS (HR 1.5, 95 % CI: 1.13–1.94) compared to controls. Subgroup analysis of immunosuppressed patients yielded similar results. Rheumatic disease activity increased post-ICI initiation (mean DAS28 Δ +0.48, p = 0.001), while rheumatologic healthcare utilization decreased.</div></div><div><h3>Conclusion</h3><div>Patients with inflammatory arthritis have poorer OS and PFS/RFS following ICI therapy for melanoma, partly attributable to baseline immunosuppressive treatment. These findings underscore the need for enhanced multidisciplinary management to optimize outcomes and address the survival gap in this population.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103400"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629556","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}
引用次数: 0
Aberrant expansion of CD177+ neutrophils promotes endothelial dysfunction in systemic lupus erythematosus via neutrophil extracellular traps
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-03-01 DOI: 10.1016/j.jaut.2025.103399
Honglin Xu , Minghua Zhan , Ziyan Wu , Jianing Chen , Yanling Zhao , Futai Feng , Fang Wang , Yongzhe Li , Shulan Zhang , Yudong Liu
{"title":"Aberrant expansion of CD177+ neutrophils promotes endothelial dysfunction in systemic lupus erythematosus via neutrophil extracellular traps","authors":"Honglin Xu ,&nbsp;Minghua Zhan ,&nbsp;Ziyan Wu ,&nbsp;Jianing Chen ,&nbsp;Yanling Zhao ,&nbsp;Futai Feng ,&nbsp;Fang Wang ,&nbsp;Yongzhe Li ,&nbsp;Shulan Zhang ,&nbsp;Yudong Liu","doi":"10.1016/j.jaut.2025.103399","DOIUrl":"10.1016/j.jaut.2025.103399","url":null,"abstract":"<div><h3>Objective</h3><div>Aberrant neutrophil activation is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and its related comorbidities. We found that <em>CD177</em> was one of the most highly up-regulated genes at the transcriptional level in purified neutrophils from SLE patients. In this study, we aimed to explore the role of CD177<sup>+</sup> neutrophils in the pathogenesis of SLE.</div></div><div><h3>Methods</h3><div>Expression of CD177 was analyzed by neutrophil transcriptome and flow cytometry. CD177<sup>+</sup> neutrophils and CD177<sup>−</sup>neutrophils were isolated to determine the role of neutrophils-derived NETs in endothelium dysfunction. Wild type and CD177<sup>−/−</sup> murine model of lupus were analyzed for organ involvement, endothelium-dependent vasorelaxation, serum autoantibodies, and innate and adaptive immune responses in an imiquimod (IMQ)-induced lupus model.</div></div><div><h3>Results</h3><div>CD177<sup>MFI-hi</sup> neutrophils and CD177<sup>MFI-hi</sup> low-density granulocytes (LDGs) were expanded in active SLE, which were weakly but significantly associated with disease activity. CD177<sup>+</sup>neutrophils displayed enhanced production of reactive oxygen species (ROS) and NETs, which impaired the murine aortic endothelium-dependent vasorelaxation and induced endothelial cell apoptosis. Moreover, CD177<sup>−/−</sup> mice exposed to IMQ showed alleviated splenomegaly, endothelium-dependent vasorelaxation, and renal immune complex deposition.</div></div><div><h3>Conclusions</h3><div>Our findings indicated that CD177 <sup>MFI-hi</sup> may serve as a novel biomarker for monitoring disease activity in SLE. Further, CD177<sup>+</sup> neutrophils may play a vasculopathic role in cardiovascular disease (CVD) via NETs formation, suggesting that specific targeting CD177<sup>+</sup> neutrophil subset may have therapeutic effect in SLE but reducing the levels of NETs-prone neutrophils.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103399"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621407","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}
引用次数: 0
Optimizing the tapering scheme of corticosteroid treatment for acute onset of autoimmune hepatitis
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-02-26 DOI: 10.1016/j.jaut.2025.103387
Rui Wang , Qiuxiang Lin , Li Sheng , Yan Zhang , Haoyu Wen , You Li , Mingxia Shi , Xiao Xiao , Li Yan , Canjie Guo , Qi Miao , Jing Hua , Zuxiong Huang , Hai Li , M. Eric Gershwin , Qixia Wang , Xiong Ma , Min Lian
{"title":"Optimizing the tapering scheme of corticosteroid treatment for acute onset of autoimmune hepatitis","authors":"Rui Wang ,&nbsp;Qiuxiang Lin ,&nbsp;Li Sheng ,&nbsp;Yan Zhang ,&nbsp;Haoyu Wen ,&nbsp;You Li ,&nbsp;Mingxia Shi ,&nbsp;Xiao Xiao ,&nbsp;Li Yan ,&nbsp;Canjie Guo ,&nbsp;Qi Miao ,&nbsp;Jing Hua ,&nbsp;Zuxiong Huang ,&nbsp;Hai Li ,&nbsp;M. Eric Gershwin ,&nbsp;Qixia Wang ,&nbsp;Xiong Ma ,&nbsp;Min Lian","doi":"10.1016/j.jaut.2025.103387","DOIUrl":"10.1016/j.jaut.2025.103387","url":null,"abstract":"<div><h3>Background</h3><div>Uncertainties persist regarding the optimal management of acute onset of autoimmune hepatitis, including the use of corticosteroids. This study aimed to compare the effectiveness and safety of rapid versus slow corticosteroid tapering in acute onset of AIH.</div></div><div><h3>Methods</h3><div>A multicenter study involving patients with acute AIH was conducted. We defined acute AIH as an acute presentation (&lt;30 days) with AIH and exhibiting no evidence of pre-existing liver diseases. Initially, corticosteroid treatment and overall outcomes were reported. Subsequently, the role of corticosteroid tapering rate in modifying outcomes across subgroups was investigated. For patients with an initial corticosteroid dose of 20 mg/day or higher, we further classified patients into rapid tapering group (duration until dose of prednisone &lt;20 mg/day &lt;3 weeks) and slow tapering group (duration until dose of prednisone &lt;20 mg/day ≥3 weeks). Adverse events were defined as any of the following events, progression (e.g., acute icteric AIH progression to AS-AIH or AIH-ALF, AS-AIH progression to AIH-ALF, non-cirrhotic progression to cirrhosis, compensated cirrhosis progression to decompensation), LT, and liver-related death.</div></div><div><h3>Results</h3><div>This retrospective cohort study enrolled 237 patients, with 109 presenting acute icteric AIH, 97 with acute-severe AIH (AS-AIH), and 31 with AIH-acute liver failure (ALF). Among patients with acute icteric AIH, slow tapering significantly improved adverse outcome-free survival compared to rapid tapering (99 % <em>vs.</em> 71 %, <em>P</em> &lt; 0.0001). Similarly, in AS-AIH patients, slow tapering resulted in notably higher adverse outcome-free survival rates compared to rapid tapering (92 % <em>vs.</em> 54 %, <em>P</em> &lt; 0.001). Slow tapering independently predicted fewer adverse events (OR 0.144; 95 % CI 0.037–0.562; <em>P</em> = 0.005). However, in AIH-acute liver failure (ALF) patients, tapering rate did not significantly affect adverse outcome-free survival (38 % <em>vs.</em> 50 %, <em>P</em> = 0.590). Overall, there were no significant differences in osteoporosis or infection occurrence between tapering groups in the entire acute AIH cohort.</div></div><div><h3>Conclusion</h3><div>A slow corticosteroid tapering reduced adverse outcomes in acute exacerbation of AIH patients, particularly in acute icteric AIH and AS-AIH.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103387"},"PeriodicalIF":7.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487593","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}
引用次数: 0
Treg fitness signatures as a biomarker for disease activity in Juvenile Idiopathic Arthritis
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-02-14 DOI: 10.1016/j.jaut.2025.103379
Meryl H. Attrill , Diana Shinko , Telma Martins Viveiros , Martina Milighetti , Nina M. de Gruijter , Bethany Jebson , Melissa Kartawinata , Elizabeth C. Rosser , Lucy R. Wedderburn , CHARMS Study , JIAP Study , Anne M. Pesenacker
{"title":"Treg fitness signatures as a biomarker for disease activity in Juvenile Idiopathic Arthritis","authors":"Meryl H. Attrill ,&nbsp;Diana Shinko ,&nbsp;Telma Martins Viveiros ,&nbsp;Martina Milighetti ,&nbsp;Nina M. de Gruijter ,&nbsp;Bethany Jebson ,&nbsp;Melissa Kartawinata ,&nbsp;Elizabeth C. Rosser ,&nbsp;Lucy R. Wedderburn ,&nbsp;CHARMS Study ,&nbsp;JIAP Study ,&nbsp;Anne M. Pesenacker","doi":"10.1016/j.jaut.2025.103379","DOIUrl":"10.1016/j.jaut.2025.103379","url":null,"abstract":"<div><div>Juvenile Idiopathic Arthritis (JIA) is an autoimmune condition characterised by flares of joint inflammation. However, no reliable biomarker exists to predict the erratic disease course. Normally, regulatory T cells (Tregs) maintain tolerance, with altered Tregs associated with autoimmunity. Treg signatures have shown promise in monitoring other conditions, therefore a Treg gene/protein signature could offer novel biomarker potential for predicting disease activity in JIA.</div><div>Machine learning on our nanoString Treg 48-gene signature on peripheral blood (PB) Tregs generated a model to distinguish active JIA (active joint count, AJC≥1) Tregs from healthy controls (HC, AUC = 0.9875 on test data). Biomarker scores from this model successfully differentiated inactive (AJC = 0) from active JIA PB Tregs. Moreover, scores correlated with clinical activity scores (cJADAS), and discriminated subclinical disease (AJC = 0, cJADAS≥0.5) from remission (cJADAS&lt;0.5).</div><div>To investigate altered protein expression as a surrogate measure for Treg fitness in JIA, we utilised spectral flow cytometry and unbiased clustering analysis. Three Treg clusters were of interest in active JIA PB, including TIGIT<sub>high</sub>CD226<sub>high</sub>CD25<sub>low</sub> Teff-like Tregs, CD39-TNFR2-Helios<sub>high</sub>, and a 4-1BB<sub>low</sub>TIGIT<sub>low</sub>ID2<sub>intermediate</sub> Treg cluster predominated in inactive JIA PB (AJC = 0). The ratio of these Treg clusters correlated to cJADAS, and higher ratios could potentially predict inactive individuals that flared by 9-month follow-up.</div><div>Thus, we demonstrate altered Treg signatures and subsets as an important factor, and useful biomarker, for disease progression versus remission in JIA, revealing genes and proteins contributing to Treg fitness. Ultimately, PB Treg fitness measures could serve as routine biomarkers to guide disease and treatment management to sustain remission in JIA.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103379"},"PeriodicalIF":7.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403727","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}
引用次数: 0
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