Autoimmunity reviews最新文献

{"title":"Adjusting fragility metrics for unequal trial randomizations","authors":"Thomas F. Heston","doi":"10.1016/j.autrev.2025.103935","DOIUrl":"10.1016/j.autrev.2025.103935","url":null,"abstract":"","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103935"},"PeriodicalIF":8.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091119","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 effect of Sphingosine-1-phosphate receptor modulator treatment on leukocyte subsets across different clinical indications: A systematic review","authors":"Dimitrios Nikolakis ,&nbsp;Christoph Teichert ,&nbsp;Joep Grootjans ,&nbsp;Marleen G.H. van de Sande ,&nbsp;Geert R. D’Haens","doi":"10.1016/j.autrev.2025.103934","DOIUrl":"10.1016/j.autrev.2025.103934","url":null,"abstract":"<div><h3>Background</h3><div>Sphingosine-1-phosphate receptor (S1PR) modulators are approved as a treatment for several autoimmune diseases. While their role on total leukocyte populations is well-studied, their effects on specific leukocyte subsets remain unclear. This systematic review describes the impact of various S1PR modulators on human leukocyte subpopulations.</div></div><div><h3>Methods</h3><div>We conducted a systematic literature search through the databases PubMed, Medline, Embase, and Cochrane, up to the 25th of July 2024. Studies were included if they involved patients treated with S1PR modulators and provided data on leukocyte subsets. Among the exclusion criteria, were non-English articles, animal studies, and in vitro studies. Data extraction focused on changes in leukocyte subsets post-treatment.</div></div><div><h3>Results</h3><div>Out of 1658 articles identified, 63 met the inclusion criteria. Fingolimod was the most frequently studied agent and displayed significant reductions in total T-cell counts. More specifically, CD4+ T-cells, including naïve and central memory populations were reduced. CD8+ T-cells also decreased, although the alterations of effector memory subsets were inconsistent. B-lymphocytes were generally attenuated. Innate immune cells showed variable responses, with most studies indicating a reduction or no change. Data on other S1PR modulators suggested similar trends.</div></div><div><h3>Conclusion</h3><div>S1PR modulators primarily reduce T- and B-cell subpopulations, which are known to play a prominent role in immune-mediated inflammatory disorders. Further research is needed to fully elucidate the differential effects among drugs targeting specific isoforms of the S1PR, focusing on the lymph nodes or inflammatory tissue sites (e.g. intestinal mucosa and cerebrospinal fluid), to explore the exact clinical implications of these pharmacodynamic findings.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103934"},"PeriodicalIF":8.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051547","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":"Exploring therapeutic potential of Cannabis based therapy in autoimmune and rheumatic disorders","authors":"Inbar Michaeli ,&nbsp;Simon Lassman ,&nbsp;Gilad Halpert ,&nbsp;Giris Jacob ,&nbsp;Howard Amital","doi":"10.1016/j.autrev.2025.103925","DOIUrl":"10.1016/j.autrev.2025.103925","url":null,"abstract":"<div><div>The medical use of cannabis is expanding across many countries, with some legalizing its use outright and others implementing medical licensure systems to approve treatment for eligible patients.</div><div>Despite this growing interest and utilization, there remains a lack of solid scientific evidence supporting its medical use, even though cannabis has been used therapeutically for thousands of years.</div><div>The goal of the following communication is to present updated data on the potential roles of cannabis-based treatments in various autoimmune and rheumatic conditions. The information highlights that incorporating cannabis into the therapeutic armamentarium may offer benefits. However, in many cases, despite encouraging perspectives and outcomes, the supporting evidence remains insufficient and requires further validation.</div><div>Due to social and legal barriers, the conduct of such rigorous clinical trials has been hindered, limiting the availability of high-quality evidence to guide medical practice.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103925"},"PeriodicalIF":8.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999505","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":"Calcium signaling dysregulation in rheumatoid arthritis: a comparative perspective with osteoarthritis","authors":"Thuy Duong Nguyen ,&nbsp;Hugo Abreu ,&nbsp;Nicoletta Tommasi ,&nbsp;Luigi Azzarone ,&nbsp;Rita Maria Concetta Di Martino ,&nbsp;Beatrice Riva ,&nbsp;Davide Raineri ,&nbsp;Tracey Pirali ,&nbsp;Annalisa Chiocchetti ,&nbsp;Giuseppe Cappellano","doi":"10.1016/j.autrev.2025.103923","DOIUrl":"10.1016/j.autrev.2025.103923","url":null,"abstract":"<div><div>Rheumatoid arthritis and osteoarthritis are among the most prevalent chronic diseases worldwide, imposing a significant burden on both patients and healthcare systems. Despite their distinct etiology and progression, emerging evidence suggests that calcium signaling plays a pivotal role in the pathogenesis of both diseases by influencing a variety of cellular processes within joint tissues. Calcium is essential for regulating key cellular functions, including gene expression, muscle contraction, cell cycle progression, proliferation, apoptosis, excitation-contraction coupling, synaptic transmission, and embryonic development. Particularly, in the context of arthritic diseases, an imbalance in calcium homeostasis has significant consequences, since the osteogenic and chondrogenic processes, as well as extracellular matrix formation, are highly influenced by calcium levels. Given these insights, a deeper understanding of the mechanisms governing calcium uptake, release, and metabolism could enhance our comprehension of disease pathogenesis and facilitate the development of novel therapeutic strategies. This review provides an overview of calcium signaling mechanisms, particularly in the most affected cells and tissues in rheumatoid arthritis and osteoarthritis, and summarizes the emerging therapies targeting calcium metabolism that may improve current treatment options.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103923"},"PeriodicalIF":8.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916341","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":"Systemic lupus erythematosus and the gut microbiome: To look forward is to look within – A systematic review and narrative synthesis","authors":"Daniel Guimarães de Oliveira ,&nbsp;Alexandra Machado ,&nbsp;Pedro Castro Lacerda ,&nbsp;Zoe Karakikla-Mitsakou ,&nbsp;Carlos Vasconcelos","doi":"10.1016/j.autrev.2025.103921","DOIUrl":"10.1016/j.autrev.2025.103921","url":null,"abstract":"<div><h3>Background</h3><div>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease shaped by complex interactions involving genetic and environmental factors. Among these, the gut microbiome is emerging as potentially modulating immune responses and influencing disease susceptibility, progression, and activity.</div></div><div><h3>Objectives</h3><div>To synthesize current evidence on gut microbiome changes in adult SLE patients, framed along the clinical pathway – from diagnosis to treatment – to help bridge bench and bedside for microbiome-informed SLE care and research.</div></div><div><h3>Methods</h3><div>A systematic search identified primary research studies examining gut microbiota in adult SLE patients. Studies were reviewed in a stepwise manner by independent investigators. Findings were synthesized narratively, emphasizing human data.</div></div><div><h3>Results</h3><div>SLE patients exhibit gut microbiome dysbiosis, with reduced microbial richness and altered bacterial taxa. A lower <em>Firmicutes</em>/<em>Bacteroidetes</em> ratio is frequently observed. Enrichment of specific taxa, such as <em>Enterococcus</em>, <em>Lactobacillus,</em> and <em>Ruminococcus gnavus,</em> is reported. Dysbiosis correlates with increased gut permeability, immune activation, and autoreactivity. Clinical associations include disease activity, flares, nephritis, and other manifestations. SLE treatments, such as hydroxychloroquine and corticosteroids, influence the microbiome. Emerging interventions such as dietary modulation and fecal microbiota transplantation show promise in early studies. However, considerable heterogeneity exists across studies in terms of patient characteristics, methodology, and taxa-level findings.</div></div><div><h3>Conclusions</h3><div>The gut microbiome has multifaceted associations with SLE pathogenesis, disease activity, and therapeutic response. Translation will require standardized methods, functional validation, longitudinal follow-up, and clinical integration. While uncertainties remain, the gut microbiome is increasingly relevant, and clinicians caring for patients with SLE should be aware of its emerging implications.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103921"},"PeriodicalIF":8.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940301","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":"Updated systematic literature review and meta-analysis to inform the Italian Society of Rheumatology Recommendations on the treatment of rheumatoid arthritis-associated interstitial lung disease","authors":"A. Fassio ,&nbsp;M. Sebastiani ,&nbsp;F. Pollastri ,&nbsp;F. Cozzini ,&nbsp;C. Crotti ,&nbsp;N. Ughi ,&nbsp;E. De Lorenzis ,&nbsp;S. Mancuso ,&nbsp;M. Radin ,&nbsp;G. Carrara ,&nbsp;G. Landolfi ,&nbsp;D. Rozza ,&nbsp;A. Manfredi","doi":"10.1016/j.autrev.2025.103922","DOIUrl":"10.1016/j.autrev.2025.103922","url":null,"abstract":"<div><h3>Background</h3><div>rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). Despite recent guideline initiatives, no treatment recommendations specifically tailored to RA-ILD have been developed in Italy. This systematic literature review (SLR) and meta-analysis was conducted to inform the Italian Society of Rheumatology (SIR) national recommendations for the management of RA-ILD.</div></div><div><h3>Methods</h3><div>we conducted a systematic review and meta-analysis of studies evaluating pharmacological interventions for RA-ILD from inception up to October 2023, followed by an update up to April 2025, with a pre-defined protocol. Eligible studies included randomized controlled trials, cohort studies, and case series reporting pulmonary function outcomes, radiological progression, adverse events, and mortality. Meta-analyses were performed, and heterogeneity and publication bias were thoroughly assessed.</div></div><div><h3>Results</h3><div>sixty-nine studies encompassing 7879 RA-ILD patients were included. Treatments with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), rituximab (RTX), mycophenolate mofetil (MMF), abatacept (ABA), and Janus kinase inhibitors (JAKi) were associated with stabilization or improvement of forced vital capacity (FVC). Methotrexate (MTX) was associated with reduced risk of ILD progression and mortality. Antifibrotics, particularly nintedanib, demonstrated variable efficacy, while pirfenidone showed limited benefit. Safety profiles favored antifibrotics over csDMARDs/immunosuppressants regarding serious adverse events.</div></div><div><h3>Conclusions</h3><div>this SLR provides an updated synthesis of evidence on RA-ILD treatments, supporting the forthcoming SIR recommendations. Despite inherent limitations of observational studies and heterogeneity, the data highlight the safety of MTX and particularly support ABA, RTX, and nintedanib as promising options, while underscoring the need for further high-quality trials specifically in RA-ILD.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103922"},"PeriodicalIF":8.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913488","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":"Hedgehog signaling pathway: A research review on a new therapeutic target for rheumatoid arthritis","authors":"Yonglin Yan ,&nbsp;Chengxia Sun ,&nbsp;Minh Hung Hoang ,&nbsp;Xiaojie Wang ,&nbsp;Yongxiang Gao","doi":"10.1016/j.autrev.2025.103918","DOIUrl":"10.1016/j.autrev.2025.103918","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint destruction, with existing therapies limited by adverse effects and incomplete efficacy. The Hedgehog signaling pathway, abnormally activated in RA, plays a pivotal pathogenic role by promoting synovial fibroblast proliferation/invasion, amplifying inflammatory responses, inducing chondrocyte matrix degradation, and enhancing angiogenesis. This review summarizes therapeutic strategies targeting this pathway, including small-molecule inhibitors (Smo/Gli antagonists), gene therapy (CRISPR-Cas, SMO-siRNA), and emerging approaches (mesenchymal stem cells, natural products). Key findings highlight the pathway's crosstalk with JAK-STAT, IL-6 signaling, and MAPK pathways, as well as challenges such as off-target tissue toxicity, drug resistance, and unclear mechanisms underlying natural product activity. Conclusion: Targeting Hedgehog signaling holds promise for RA therapy, with future directions focusing on optimizing synovium-specific delivery, exploring combination regimens, and clarifying cell-type-specific regulatory mechanisms to accelerate clinical translation.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103918"},"PeriodicalIF":8.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913489","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 roles of S100A8/A9 and S100A12 in autoimmune diseases: Mechanisms, biomarkers, and therapeutic potential","authors":"Xiaoqing Wang ,&nbsp;Ying Luo ,&nbsp;Qiang Zhou ,&nbsp;Jie Ma","doi":"10.1016/j.autrev.2025.103920","DOIUrl":"10.1016/j.autrev.2025.103920","url":null,"abstract":"<div><div>The S100 protein family, the largest group of calcium-binding proteins, functions as key molecular regulators both intracellularly and extracellularly. Among these, S100A8/A9 and S100A12 have gained particular attention for their roles in the pathogenesis of autoimmune diseases (AID). These proteins interact with pivotal receptors, including G-protein-coupled receptors (GPCRs), toll-like receptor-4 (TLR4), and receptor for advanced glycation end-products (RAGE), driving innate immune activation, amplifying inflammatory responses, and modulating immune cell function. Dysregulation of S100A8/A9 and S100A12 is closely associated with disease progression across multiple autoimmune conditions. Their elevated expression correlates with disease severity, making them valuable biomarkers for monitoring disease activity, predicting therapeutic responses, and assessing disease progression. This review provides an in-depth synthesis of current evidence on the mechanistic roles of S100A8/A9 and S100A12 in AID, emphasizing their biomarker potential and therapeutic value. We further discuss emerging therapeutic strategies that target S100 proteins, their receptors, downstream signaling pathways using small-molecule inhibitors, RNA-based approaches, and monoclonal antibodies. These insights highlight the dual promise of S100A8/A9 and S100A12 as both disease indicators and intervention points, offering novel avenues for the management of AID.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103920"},"PeriodicalIF":8.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908590","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":"Artificial intelligence for biopsies and imaging modalities in systemic autoimmune rheumatic diseases: An instructive narrative review","authors":"Konstantinos N. Panagiotopoulos ,&nbsp;Nikos Tsiknakis ,&nbsp;Dimitrios I. Zaridis ,&nbsp;Athanasios G. Tzioufas ,&nbsp;Dimitrios I. Fotiadis ,&nbsp;Andreas V. Goules","doi":"10.1016/j.autrev.2025.103916","DOIUrl":"10.1016/j.autrev.2025.103916","url":null,"abstract":"<div><h3>Purpose</h3><div>To organize the existing literature regarding applications of artificial intelligence (AI) in biopsies and imaging modalities of patients with systemic autoimmune rheumatic diseases (SARDs) and to familiarize readers with the most commonly occurring concepts.</div></div><div><h3>Results</h3><div>Firstly, we present a workflow that summarizes techniques implemented in AI for biopsies and imaging modalities in SARDs. Next, we describe challenges specific to image analysis for medicine. Subsequently, we describe the goals for an AI study in this field, and the prerequisites to meet them in SARDs. Finally, after reviewing the existing literature, we present the applications of AI for image analysis in each SARD. Accordingly, we analyze 1–2 studies from each SARD and mention key messages and lessons derived from them. Lastly, we create a recommendation landscape identifying unmet needs for AI applications in each SARD. The vast majority of studies employ supervised learning for image classification or segmentation, and rarely for regression. The median dataset size was 116 patients for imaging studies and 271 patients for biopsies studies, while the number of images per study varied greatly. Reporting of multiple performance metrics was frequently neglected.</div></div><div><h3>Conclusions</h3><div>Employing AI for SARD image analysis ultimately demands large datasets with multimodal and adequately diverse data to effectively capture the heterogeneity of SARDs. In the field of rheumatology, plagued by subjectivity and interobserver variability, issues regarding data quality, regulatory authorities and the specificity and clinical impact of questions posed will define the time needed for clinical adoption of AI-assisted medical care.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103916"},"PeriodicalIF":8.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908577","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 fragility of randomized controlled trials in large vessel vasculitis","authors":"Durga Prasanna Misra ,&nbsp;Chetan B. Mukhtyar ,&nbsp;Kunal Chandwar ,&nbsp;Michael Putman ,&nbsp;Michael Walsh","doi":"10.1016/j.autrev.2025.103917","DOIUrl":"10.1016/j.autrev.2025.103917","url":null,"abstract":"<div><div>The fragility of randomized controlled trials (RCTs) of large vessel vasculitis (LVV) – defined as the minimum number of outcome events that would need to change to reverse the trial's conclusions - has not been comprehensively studied. We identified relevant RCTs with a systematic literature review till April 2025. The fragility index (FI)/ reverse fragility index (RFI) and fragility quotient (FQ, i.e., FI or RFI divided by number of trial participants) were calculated for primary or key secondary outcomes. Subgroup analyses were based on risk of bias (Cochrane Risk of Bias 2), drug (biologic or targeted synthetic agent versus other), LVV subtype, and time of publication (before/ after 2015). Eighteen RCTs (GCA, <em>n</em> = 14; TAK, <em>n</em> = 4) were analyzed. For trials with significant outcomes, FI ranged from 1 to 12 and FQ from 0.019 to 0.150; 5/9 (56 %) had FI ≤3, and 8/9 (89 %) had FQ ≤0.1. For trials with non-significant primary outcome, RFI ranged from 1 to 9 and FQ from 0.009 to 0.330; 8/12 (67 %) had RFI ≤5, 6/12 (50 %) had FQ ≤0.1, and 4/12 (33 %) had RFI less than the number lost to follow-up. The FI, RFI and FQ were similar for trials based on risk of bias, drug, LVV subtype, or time of publication. The results of most published LVV trials are fragile suggesting treatments are at risk of being misclassified as effective or ineffective. Larger trials with more robust and validated outcome measures or alternate designs should be considered in future LVV trials to improve confidence in their assessments of treatment effects.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 12","pages":"Article 103917"},"PeriodicalIF":8.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913491","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}