Autoimmunity reviews最新文献

{"title":"Dual B-cell targeting in systemic lupus erythematosus: The role of combined and sequential therapy with rituximab and belimumab","authors":"Beatriz Frade-Sosa ,&nbsp;Juan C. Sarmiento-Monroy ,&nbsp;Ian N. Bruce ,&nbsp;Laurent Arnaud ,&nbsp;José A. Gómez-Puerta","doi":"10.1016/j.autrev.2025.103837","DOIUrl":"10.1016/j.autrev.2025.103837","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by immune dysregulation and autoantibody production. Despite advances in treatment, achieving sustained disease control remains challenging. Rituximab (RTX) and belimumab (BELI) are two B-cell-targeting biologics with complementary mechanisms of action, leading to increasing interest in their combination as a therapeutic strategy for refractory SLE. RTX depletes CD20+ B cells, whereas BELI inhibits B-lymphocyte stimulator (BLyS), reducing the survival of autoreactive B cells. Sequential therapy with these agents may mitigate B-cell repopulation and improve disease control.</div><div>Recent studies, including SynBioSe and BEAT-LUPUS, suggest that RTX-BELI therapy can reduce autoantibody levels, neutrophil extracellular trap formation, and disease activity, with many patients achieving a lupus low disease activity state (LLDAS). However, the BLISS-BELIEVE and CALIBRATE trials did not demonstrate superiority over monotherapy, highlighting the need to refine patient selection. Combination therapy may be particularly beneficial in lupus nephritis, where BELI delays autoreactive B-cell reconstitution following RTX, potentially prolonging remission.</div><div>While RTX-BELI therapy is generally well-tolerated, some studies report increased infections, necessitating careful patient monitoring. Lessons from other immune-mediated diseases, including inflammatory bowel disease and rheumatoid arthritis, underscore the potential benefits and risks of dual biologic therapy. Further research, including the ongoing SynBioSe-2 trial, is needed to clarify the optimal use, sequencing, and safety profile of RTX-BELI in SLE. Identifying biomarkers predictive of response may enable personalized treatment approaches, ultimately improving long-term outcomes for patients with refractory SLE.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103837"},"PeriodicalIF":9.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141325","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":"Experiences and unmet needs of persons living with systemic lupus erythematosus in Europe: Lupus Europe's 2024 Swiss knife survey","authors":"Alain Cornet ,&nbsp;Zoe Karakikla Mitsakou ,&nbsp;Jeanette Andersen ,&nbsp;Sarah Dyball ,&nbsp;Ricky Chotai ,&nbsp;Annemarie Sluijmers ,&nbsp;Cristiana Sieiro Santos ,&nbsp;Aldevina Sturiene ,&nbsp;Lucy Scarle ,&nbsp;Daniel Guimarães de Oliveira ,&nbsp;Nuria Zuniga ,&nbsp;Elfriede Wijsma ,&nbsp;Elisabetta Chessa ,&nbsp;Laurent Arnaud","doi":"10.1016/j.autrev.2025.103838","DOIUrl":"10.1016/j.autrev.2025.103838","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a complex autoimmune disease with important variations in disease burden across patients and European countries. In response to previous surveys revealing the burden of SLE on patients, Lupus Europe conducted the 2024 ‘Swiss Knife’ survey to further investigate disease burden, treatment goals, and patient-physician interactions in European patients living with lupus. Between April and May 2024, 4525 patients with self-reported physician-confirmed SLE across 36 European countries participated in an anonymous online study. Descriptive statistics were utilized to analyze responses related to SLE symptoms, treatment satisfaction, and unmet needs. Results indicated that fatigue (84.9 %), joint pain (72.8 %), and muscle pain (62.6 %) were the most prevalent symptoms, with fatigue notably under-addressed in treatment plans. The mean lupus burden score was high at 6.94 (SD: 1.95) on the 0–10 scale, highlighting a significant impact on quality of life, particularly in terms of fatigue and physical consequences. Notably, only 7.9 % of participants reported no disease flares in the past five years, contrasting with previous literature on remission rates. In terms of treatment goals, patients favored achieving low disease activity or remission without treatment, while satisfaction with current therapies was moderate, with 67.5 % expressing contentment but many indicating unmet needs, particularly regarding fatigue management and access to non-pharmacological therapies. The findings of Lupus Europe's 2024 Swiss Knife study underscore the necessity for improved communication between patients and healthcare professionals and the integration of patient-centered strategies to optimize SLE management and enhance quality of life across Europe.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103838"},"PeriodicalIF":9.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126454","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":"Integrating network pharmacology and experimental validation to advance psoriasis treatment: Multi-target mechanistic elucidation of medicinal herbs and natural compounds","authors":"Hee-Geun Jo ,&nbsp;Jihye Seo ,&nbsp;Boyun Jang ,&nbsp;Youngsoo Kim ,&nbsp;Hyehwa Kim ,&nbsp;Eunhye Baek ,&nbsp;Soo-Yeon Park ,&nbsp;Donghun Lee","doi":"10.1016/j.autrev.2025.103836","DOIUrl":"10.1016/j.autrev.2025.103836","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis, a chronic immune-mediated inflammatory disease (IMID), presents significant therapeutic challenges, necessitating exploration of alternative treatments like medicinal herbs (MH) and natural compounds (NC). Network pharmacology offers predictive insights, yet a systematic evaluation connecting these predictions with experimental validation outcomes specifically for MH/NC in psoriasis is lacking. This review specifically fills this gap by comprehensively integrating and analyzing studies that combine network pharmacology predictions with subsequent experimental validation.</div></div><div><h3>Methods</h3><div>A systematic literature search identified 44 studies employing both network pharmacology and in vitro or in vivo experimental methods for MH/NC targeting psoriasis. This review provides a systematic analysis of the specific network pharmacology platforms, predicted targets/pathways, in vivo and in vitro experimental validation models, and key biomarker changes reported across these integrated studies. Methodological approaches and the consistency between predictions and empirical findings were critically evaluated.</div></div><div><h3>Results</h3><div>This first comprehensive analysis reveals that network pharmacology predictions regarding MH/NC mechanisms in psoriasis are frequently corroborated by experimental data. Key signaling pathways, including the IL-17/IL-23 axis, MAPK, and NF-κB, emerge as consistently predicted and experimentally validated targets across diverse natural products. The review maps the specific network pharmacology tools and experimental designs utilized, establishing a methodological benchmark for the field and highlighting the successful synergy between computational prediction and empirical verification.</div></div><div><h3>Conclusion</h3><div>By systematically integrating and critically assessing the linkage between network pharmacology predictions and experimental validation for MH/NC in psoriasis, this review offers a unique clarification of the current, validated state-of-the-art, differentiating it from previous literature. It confirms network pharmacology's predictive power for natural products, identifies robustly validated therapeutic pathways, and provides a crucial benchmark, offering data-driven insights for future research into artificial intelligence-enhanced natural product-based therapies for psoriasis and other IMIDs.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103836"},"PeriodicalIF":9.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092032","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":"New thoughts on the intestinal microbiome-B cell-IgA axis and therapies in IgA nephropathy","authors":"Shaoqing Dang ,&nbsp;Xiangyu Zhang ,&nbsp;Yuemiao Zhang ,&nbsp;Hong Zhang","doi":"10.1016/j.autrev.2025.103835","DOIUrl":"10.1016/j.autrev.2025.103835","url":null,"abstract":"<div><div>IgA nephropathy (IgAN), as the most common chronic glomerulonephritis worldwide, is often triggered by mucosal infections and follows a chronic progression, with the majority of patients ultimately progressing to end-stage renal disease (ESRD) during their lifetimes. Since the mystery of its complete pathogenesis has not been fully solved, the resulting lack of effective early diagnosis and treatment greatly affects the prognosis of patients. Given the well-defined pathological feature of IgA deposition in the mesangial region, the source and role of pathogenic IgA has been focused on. Starting from the microbiology and immunity of the gut, we systematically review both the physiological and the pathological process of microbiome-B cell-IgA axis, from microbial-induced IgA production to the role of IgA in the intestinal immune milieu, and ultimately end up with the various aspects of microbiome-B cell-IgA axis in the pathogenesis of IgAN as well as the corresponding therapeutic initiatives available. Our retrospective review helps researchers to systematically understand the complex role between intestinal flora dysbiosis and pathogenic IgA in IgAN. This understanding provides a foundation for in-depth explorations to uncover more detailed pathogenic mechanisms and to develop more precise and effective diagnostic and therapeutic approaches.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103835"},"PeriodicalIF":9.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966179","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":"Safety of biologics in patients with autoimmune rheumatic diseases during pregnancy: Systematic review and meta-analysis","authors":"Shiran Li ,&nbsp;Hongxi Liu ,&nbsp;Siyu Zeng ,&nbsp;Jingxian Xie ,&nbsp;Zhimin Li ,&nbsp;Yong Yang ,&nbsp;Junlan Chuan","doi":"10.1016/j.autrev.2025.103827","DOIUrl":"10.1016/j.autrev.2025.103827","url":null,"abstract":"<div><h3>Background</h3><div>Patients with autoimmune rheumatic diseases (ARDs) face the dual challenge of controlling disease activity while ensuring fetal safety during pregnancy. Biologics are increasingly used to treat ARDs, but evidence regarding their safety during pregnancy remains uncertain. This study aims to systematically evaluate the safety of biologics during pregnancy by performing a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>A comprehensive search was conducted in major databases to identify studies involving pregnant ARDs patients treated with biologics from inception to 30th September 2024. The outcomes assessed included small for gestational age (SGA), cesarean section, preterm birth (PTB), low birth weight (LBW), gestational diabetes mellitus (GDM), pre-eclampsia, gestational hypertension, severe maternal infection, birth defects (BD), and a composite outcome of fetal miscarriage or death.</div></div><div><h3>Results</h3><div>A total of 40 studies involving 11,712 patients were included. The pooled prevalence of adverse pregnancy outcomes (APOs) in patients exposed to biologics was comparable to those observed in the general ARDs population. Compared to other biologics, tumor necrosis factor inhibitors (TNFis) was associated with a significantly lower prevalence of cesarean section (26.93 % vs. 63.64 %, <span><math><mi>p</mi></math></span> = 0.01), early pregnancy loss (10.44 % vs. 18.77 %, <span><math><mi>p</mi></math></span> = 0.03), and termination of pregnancy (8.59 % vs. 16.11 %, <span><math><mi>p</mi></math></span> &lt; 0.01). Compared to csDMARDs, biologic use during pregnancy did not significantly increase the risk of APOs.</div></div><div><h3>Conclusion</h3><div>Exposure to biologics during pregnancy in ARDs patients does not significantly increase the risk of APOs, with TNFis showing a well-supported safety profile, while non-TNFi biologics may carry higher risks, requiring cautious evaluation.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103827"},"PeriodicalIF":9.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936245","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":"Interleukin-6 in neuroimmunological disorders: Pathophysiology and therapeutic advances with satralizumab","authors":"Xicheng Li ,&nbsp;Chongbo Zhao","doi":"10.1016/j.autrev.2025.103826","DOIUrl":"10.1016/j.autrev.2025.103826","url":null,"abstract":"<div><div>Interleukin-6 (IL-6) is a multifunctional cytokine produced by various cells of the innate and adaptive immune systems. It acts as a regulatory factor in immunity, inflammation, metabolism, and cellular function in multiple organs and systems. The functionality of IL-6 is achieved through multiple signal transduction pathways, such as the JAK/STAT and the NF-κB signaling pathways. In this review, we highlighted the inflammatory and non-inflammatory functions of IL-6, as well as the associated signaling pathways. The involvement of IL-6 in neuroimmunological disorders suggests that the interleukin-6 receptor (IL-6R) monoclonal antibody, satralizumab, is a potential therapeutic strategy. Phase III clinical trials have already validated the safety and efficiency of satralizumab in treating neuromyelitis optica spectrum disorders (NMOSD) and acetylcholine receptor (AChR) seropositive generalized myasthenia gravis (gMG). This review aims to elucidate the pathophysiological role of IL-6, and explore the clinical implications of satralizumab in neuroimmunological diseases, providing insights into its potential therapeutic applications.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103826"},"PeriodicalIF":9.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905881","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":"Adipokines in multiple sclerosis: Immune dysregulation, neuroinflammation, and therapeutic opportunities","authors":"Elham Moases Ghaffary ,&nbsp;Geir Bjørklund ,&nbsp;Ramesa Shafi Bhat ,&nbsp;Omid Mirmosayyeb","doi":"10.1016/j.autrev.2025.103825","DOIUrl":"10.1016/j.autrev.2025.103825","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS), characterized by demyelination, neuroinflammation, and the progressive accumulation of neurologic deficits. Adipose tissue secretes predominantly the bioactive molecules, known as adipokines, which have drawn considerable attention for their roles in modulating immune and metabolic pathways in people with MS (PwMS). Dysregulated adipokines, such as resistin, leptin, and chemerin, induce pro-inflammatory T-cell polarization while deteriorating Blood-Brain Barrier (BBB) integrity. Adiponectin, by contrast, has both immunomodulatory and neuroprotective functions. The opposing functionality highlights the biomarker and the therapeutic potential of adipokines. Preclinical and translational findings have shed light on the role of adipokines in the pathophysiology of MS by influencing T-cell, glial, and BBB functions. In clinical settings, the assessment of adipokines can function as an indicator of prognosis and diagnosis via distinct patterns of expression. In addition, alterations to adipokine profiles through lifestyle changes and pharmaceutical treatment may complement established disease-modifying treatments (DMTs). This study has highlighted the multifaceted role of adipokines in MS management, while further studies exploring the role of adipokine-mediated immunometabolic regulation are suggested.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 8","pages":"Article 103825"},"PeriodicalIF":9.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948553","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 emerging concept of ANCA-associated vasculitis related to inborn errors of immunity","authors":"Clément Triaille ,&nbsp;Benjamin Terrier ,&nbsp;Alice Hadchouel ,&nbsp;Elie Haddad ,&nbsp;Augusto Vaglio ,&nbsp;Marie-Louise Frémond","doi":"10.1016/j.autrev.2025.103824","DOIUrl":"10.1016/j.autrev.2025.103824","url":null,"abstract":"<div><div>ANCA-associated vasculitis (AAV) is a group of rare small vessels vasculitis that preferentially affect the kidneys, lungs and upper airways. Although the detailed pathophysiology remains unclear, genetic background has been shown to play a role in sporadic forms of AAV. The discovery of these susceptibility genes (and associated biological pathways) involved in AAV have shaped the current understanding of AAV pathophysiology. In addition to common genetic polymorphisms, specific rare inborn errors of immunity (IEI) have been described with a high frequency of ANCA (antineutrophil cytoplasmic antibodies) positivity and vasculitis features in young individuals (in addition to other manifestations). A systematic literature search revealed that patients with pathogenic variants in <em>COPA, STING1, DNASE1L3,</em> and <em>PIK3CD</em> are at increased risk of developing ANCA and AAV features, including alveolar hemorrhage, interstitial lung disease, pauciimmune glomerulonephritis, and upper airways involvement (septum perforation, saddle-nose deformity, chronic nasal/sinuses ulceration). Some of these IEI may also present with a mixed phenotype and/or auto-antibodies profile associating features of AAV and other autoimmune diseases (in particular systemic lupus erythematosus). Notably, a proportion of reports and series lack serological (ANCA specificity and titers) and/or histopathological data, making challenging to assess the likelihood for ANCA pathogenicity in some patients with IEI (as opposed to unspecific signs of biologic autoimmunity). This point is nonetheless essential to make appropriate therapeutic decisions. In addition, since most of the genes mentioned above are involved in the type 1 interferon signaling, the role of this pathway in AAV etiopathogenesis deserves further investigation.</div><div>In this review, we will describe these IEI, their overlap with sporadic AAV, and their evocative features. Next, we will discuss how these monogenic conditions might inform our general understanding of AAV pathophysiology. We also propose some directions for future research in order to better define the link between ANCA and IEI. Finally, we will consider how making the diagnosis of an IEI in a patient with AAV features might impact individual management.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103824"},"PeriodicalIF":9.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894301","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":"Coffee consumption and risk of multiple sclerosis: A systematic review and meta-analysis","authors":"Mehrad Amirnia ,&nbsp;Khazar Raeisnia ,&nbsp;Hamidreza Ashayeri ,&nbsp;Zahra Hakimzadeh ,&nbsp;Ehsan Nasiri ,&nbsp;Mahnaz Talebi ,&nbsp;Sarvin Sanaie ,&nbsp;Amirreza Naseri","doi":"10.1016/j.autrev.2025.103822","DOIUrl":"10.1016/j.autrev.2025.103822","url":null,"abstract":"<div><h3>Background</h3><div>Multiple Sclerosis (MS) is an immune-mediated disease with miscellaneous etiological origins. Given caffeine's neuroprotective and anti-inflammatory attributes and its potential influence on MS risk, and to address the conflict in the clinical evidence, this study aims to comprehensively review the existing literature on the association between coffee consumption and the risk of MS.</div></div><div><h3>Methods</h3><div>Following the PRISMA 2020 guidelines, a systematic search in PubMed, Scopus, Web of Science, and Embase for the studies published up to January 2024 was conducted. Studies that assessed the relationship between coffee intake and the risk of MS were included, and reviews, case reports, non-English papers, in vitro and animal studies, and conference abstracts were excluded. The risk of bias was assessed using the JBI checklists, and meta-analyses were conducted based on odds ratio (OR) using the fourth version of CMA software.</div></div><div><h3>Results</h3><div>Out of 604 initial records, 10 observational studies with 19,430 participants met the inclusion criteria. The included case-control studies showed an overall high quality. Meta-analysis revealed a reduction in MS development in coffee consumers both before (OR: 0.66; 95 % CI: 0.49–0.90; <em>p</em>-value: 0.008; I²: 89.65 %; p-value for heterogeneity&lt;0.001) and after adjustment for possible confounders (adjusted OR: 0.42; 95 % CI: 0.20–0.90; p-value: 0.025; I²: 89.65 l; p-value for heterogeneity&lt;0.001).</div></div><div><h3>Conclusion</h3><div>Coffee consumption, may decrease the risk of MS; however, further well-designed prospective studies are required to ascertain this association.</div><div>PROSPERO registration number: CRD42023484298.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 7","pages":"Article 103822"},"PeriodicalIF":9.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887886","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":"Rebalancing redox homeostasis: A pivotal regulator of the cGAS-STING pathway in autoimmune diseases","authors":"Yuchen Zhao ,&nbsp;Tianhao Xu ,&nbsp;Zhaoshun Wu ,&nbsp;Ning Li ,&nbsp;Qianqian Liang","doi":"10.1016/j.autrev.2025.103823","DOIUrl":"10.1016/j.autrev.2025.103823","url":null,"abstract":"<div><div>Autoimmune diseases (ADs) arise from the breakdown of immune tolerance to self-antigens, leading to pathological tissue damage. Proinflammatory cytokine overproduction disrupts redox homeostasis across diverse cell populations, generating oxidative stress that induces DNA damage through multiple mechanisms. Oxidative stress-induced alterations in membrane permeability and DNA damage can lead to the recognition of double-stranded DNA (dsDNA), mitochondrial DNA (mtDNA) and micronuclei-DNA (MN-DNA) by DNA sensors, thereby initiating activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. While previous reviews have characterized cGAS-STING activation in autoimmunity, the reciprocal regulation between redox homeostasis and cGAS-STING activation remains insufficiently defined. This narrative review examines oxidative stress-mediated DNA damage as a critical driver of pathological cGAS-STING signaling and delineates molecular mechanisms linking redox homeostasis to autoimmune pathogenesis. Furthermore, we propose therapeutic strategies that combine redox restoration with the attenuation of aberrant cGAS-STING activation, thereby establishing a mechanistic foundation for precision interventions in autoimmune disorders.</div></div><div><h3>Methods</h3><div>The manuscript is formatted as a narrative review. We conducted a comprehensive search strategy using electronic databases such as PubMed, Google Scholar and Web of Science. Various keywords were used, such as \"cGAS-STING,\" \"Redox homeostasis,\" \"Oxidative stress,\" \"pentose phosphate pathway,\" \"Ferroptosis,\" \"mtDNA,\" \"dsDNA,\" \"DNA damage,\" \"Micronuclei,\" \"Reactive oxygen species,\" \"Reactive nitrogen species,\" \"Nanomaterial,\" \"Autoimmune disease,\" \"Systemic lupus erythematosus,\" \"Type 1 diabetes,\" \"Rheumatoid arthritis,\" \"Multiple sclerosis,\" \"Experimental autoimmune encephalomyelitis,\" \"Psoriasis,\" etc. The titles and abstracts were reviewed for inclusion into this review. After removing duplicates and irrelevant studies, 174 articles met inclusion criteria (original research, English language).</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 6","pages":"Article 103823"},"PeriodicalIF":9.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902534","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}