Autoimmunity reviews最新文献

{"title":"Impact of GLP-1 analogues on immune-mediated inflammatory diseases: A systematic review","authors":"Chhagan L. Birda ,&nbsp;Fadwa Ibrahim ,&nbsp;Abhirup Chatterjee ,&nbsp;Anuraag Jena ,&nbsp;Vishal Sharma ,&nbsp;Shaji Sebastian","doi":"10.1016/j.autrev.2025.103936","DOIUrl":"10.1016/j.autrev.2025.103936","url":null,"abstract":"<div><h3>Objective</h3><div>Glucagon-like peptide-1 receptor agonists (GLP1RA) are believed to have anti-inflammatory properties apart from antidiabetic and anti-obesity effects.</div></div><div><h3>Methods</h3><div>We performed a systematic review to evaluate the efficacy and safety of GLP1RA in immune-mediated inflammatory disorders (IMIDs). A systematic search was done on 3rd April 2025 in PubMed, Scopus, and Embase for studies reporting the use of GLP1RA among patients with IMIDs. Because of significant heterogeneity and overlapping data originating from the same insurance databases, we decided against performing a data synthesis and meta-analysis. We summarised the data regarding clinical and metabolic outcomes in patients with IMIDs with/without the use of GLP1RA.</div></div><div><h3>Results</h3><div>Thirty-three studies (20 full text, 13 conference abstracts) were included, of which 20 studies focused on inflammatory bowel disease (IBD) and 13 on other IMIDs. Of the three studies reporting on new onset IBD/IMID in GLP1RA users, 2 showed a lower incidence. IBD therapy utilization was reported in 13 studies; steroid use was lower in 5 studies, but the data on the use of biologics were inconclusive. Other outcomes, like hospitalization, IBD complications, surgery, and mortality, seemed to be better in GLP1RA cohorts in a few of the studies. Similarly, psoriasis disease activity-related outcomes were better in the GLP1RA cohort, but the effect on other IMIDs was limited by sparse literature. A total of 12 studies reported metabolic outcomes, including weight loss, glycaemic control, waist circumference, and lipid parameters, all of which showed beneficial effects of GLP1RAs, and these results were comparable to non-IBD/IMID controls. Adverse events (AEs) were reported by 13 studies; gastrointestinal (GI) AEs were higher in the GLP1RA cohort (but the majority were non-severe).</div></div><div><h3>Conclusion</h3><div>GLP1RA use is associated with better disease activity and metabolic outcomes in patients with IMIDs and concomitant metabolic disorders.</div><div>Registration: <span><span>https://osf.io/jvmz6</span><svg><path></path></svg></span></div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103936"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278829","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":"Sex-specific mechanisms in the pathogenesis and progression of chronic kidney disease","authors":"Guangtao Li ,&nbsp;Zhiwei Xu ,&nbsp;Hongxia Yang ,&nbsp;Dan Zhang ,&nbsp;Bin Liu ,&nbsp;Yifan Song ,&nbsp;Qianhui Li ,&nbsp;Yanghe Zhang ,&nbsp;Honglan Zhou ,&nbsp;Yishu Wang","doi":"10.1016/j.autrev.2025.103938","DOIUrl":"10.1016/j.autrev.2025.103938","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is a growing global public health concern, marked by increasing prevalence and substantial economic burden. Notably, CKD demonstrates significant physiological sex differences. Epidemiological evidence indicates that men are more susceptible to developing CKD in early to middle adulthood due to accelerated declines in renal function, whereas postmenopausal women exhibit a sharp rise in CKD incidence and progression. These findings suggest that sex hormones may play a critical regulatory role in CKD pathogenesis. The “bidirectional effects” of sex hormones are considered a fundamental mechanism driving these sex-based disparities. Androgens exacerbate renal inflammation and fibrosis by activating the TGF-β/TNF-α axis and the renin–angiotensin–aldosterone system (RAAS)/20-HETE pathway, in concert with NLRP3 inflammasome activation, thereby worsening glomerular hypertension and metabolic dysfunction. In contrast, estrogens exert protective effects by inhibiting RAAS activity, upregulating the ACE2/Ang-(1–7) pathway, activating the GPER/Sirt1 signaling network, and enhancing antioxidant capacity, thereby preserving renal hemodynamic homeostasis. Furthermore, this review incorporates a range of additional factors—including hormone-like compounds, sex-specific gut microbiota–host metabolic interactions, sex chromosome inactivation or loss, ectopic lipid deposition, and unfavorable lifestyle behaviors—to construct a comprehensive pathological model of sex-specific CKD progression. Elucidating the mechanisms by which sex differences influence kidney disease, and identifying sex-dependent contributors to CKD onset and advancement, may provide critical insights for developing personalized therapeutic strategies.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103938"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312134","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":"Are the 2023 ACR/EULAR classification criteria a step forward in the management of antiphospholipid syndrome? A literature-based and clinical practice appraisal","authors":"Jaume Alijotas-Reig ,&nbsp;Joana Marques-Soares ,&nbsp;Enrique Esteve-Valverde ,&nbsp;Ariadna Anunciación-Llunell ,&nbsp;Catalina Andrada ,&nbsp;Monika Ockova ,&nbsp;Ariella Hoxha ,&nbsp;Munther A. Khamashta ,&nbsp;Yehuda Shoenfeld ,&nbsp;Francesc Miró-Mur","doi":"10.1016/j.autrev.2025.103956","DOIUrl":"10.1016/j.autrev.2025.103956","url":null,"abstract":"<div><div>Antiphospholipid syndrome (APS) is an autoimmune disease (AID) without defined diagnostic criteria, but having classification criteria, as happens in most AID. Until 2023, we were using 2006 Sydney classification criteria. Although they had a research purposes, in the real life they have been used as a diagnostic tool, equating classification with diagnostic. From July 2023, these criteria were revisited by American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) panel of experts. This recently reported set of classification criteria underlie that only should be used for research purposes. They prioritises specificity ̵ 99 % ̵ at the cost of sensitivity ̵ 84 % ̵ ACR/EULAR criteria consider 6 clinical and 2 laboratory domains. Although new clinical items have been included, improving overall the inclusion of patients and, indirectly diagnosis, i.e., thrombocytopenia, cardiac valvular involvement and microvascular thrombosis, a remarkable number of patients with putative aPL-related disorders could leave out of classification as having APS, and in the real life, losing the opportunity to manage them appropriately. Consequently, these patients will be prone to suffer new events, thrombotic or obstetric, as have been already demonstrated.</div><div>This manuscript focuses on the pros and cons of the clinical and laboratory domains of these new criteria and their impact not only on the clinical point of view, but also in the APS research field.</div><div>Using 6 clinical cases, we provide readers with a sense of diagnostic certainties and uncertainties, and their shortcomings in the context of the ACR/EULAR APS classification.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103956"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421149","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":"Environmental toxins and toxic metals in autoimmune diseases: Sex differences, hormonal influences, and immune dysregulation","authors":"Geir Bjørklund ,&nbsp;David R. Wallace ,&nbsp;Kimiya Kangarlou ,&nbsp;Fahimida Hossain ,&nbsp;Massimiliano Peana","doi":"10.1016/j.autrev.2025.103955","DOIUrl":"10.1016/j.autrev.2025.103955","url":null,"abstract":"<div><div>Environmental toxins, including toxic metal(<em>oid</em>)s such as mercury, lead, cadmium, and arsenic, as well as endocrine-disrupting chemicals like bisphenol A and phthalates, play a critical role in the onset and progression of autoimmune diseases. These substances accumulate in biological tissues and disrupt immune homeostasis through oxidative stress, molecular mimicry, and epigenetic modifications, mechanisms that contribute to autoantibody production and chronic inflammation, hallmarks of autoimmunity. Women are disproportionately affected by autoimmune diseases due to inherent differences in immune function, hormonal regulation, and genetic susceptibility. Estrogen, a key immunomodulatory hormone, can amplify immune responses and promote autoantibody generation. Its interaction with environmental toxins further exacerbates immune dysregulation, increasing female vulnerability to conditions such as systemic lupus erythematosus, rheumatoid arthritis, and autoimmune thyroid disorders. Hormonal fluctuations during puberty, pregnancy, and menopause additionally influence toxin metabolism and detoxification efficiency, compounding the risk of immune imbalance and disease onset in women. This review synthesizes current evidence on the mechanisms through which environmental toxicants contribute to autoimmune pathogenesis, with particular focus on sex-specific vulnerabilities. It explores the role of hormonal-immune-environment interactions across the female lifespan and highlights emerging research on epigenetic inheritance, gut dysbiosis, and biomarker development. By integrating mechanistic, epidemiological, and clinical findings, this review aims to inform targeted strategies for prevention, early detection, and risk reduction of environmentally driven autoimmune diseases.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103955"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421205","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":"Immune checkpoint inhibitor-induced inflammatory arthritis vs rheumatoid arthritis: A comparative review","authors":"Iliopoulos Georgios ,&nbsp;Sideridou Fani ,&nbsp;Bogdanos Dmitrios ,&nbsp;Liew David ,&nbsp;Daoussis Dimitrios","doi":"10.1016/j.autrev.2025.103943","DOIUrl":"10.1016/j.autrev.2025.103943","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of oncology but are frequently accompanied by immune-related adverse events (irAEs). Among these, ICI-induced inflammatory arthritis (ICI-IA) has emerged as the most common musculoskeletal toxicity, often mimicking rheumatoid arthritis (RA) in its clinical and imaging features. This narrative review synthesizes current evidence comparing ICI-IA with RA across epidemiology, pathophysiology, clinical presentation, imaging, treatment, and prognosis. While both entities share overlapping manifestations such as polyarthritis, synovitis, and joint erosions, ICI-IA is typically seronegative, arises subacutely after ICI initiation, and exhibits distinct immunopathologic signatures, including cytotoxic CD8+ T-cell predominance and unique B-cell alterations. ICI-IA may persist after ICI cessation, with chronic disease linked to improved oncologic outcomes. Therapeutic strategies require balancing arthritis control and preservation of anti-tumor immunity. Glucocorticoids and conventional disease modifying anti-rheumatic drugs (cDMARDs) are key players with proven safety and efficacy, whereas biologic therapies remain reserved for severe or refractory cases mainly due to cancer progression concerns. Furthermore, early rheumatology referral improves patient outcomes and reduces glucocorticoid exposure. Understanding the differences between ICI-IA and RA is essential for optimizing diagnosis, guiding individualized approach and applying precision medicine at the crossroads of oncology and rheumatology.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103943"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336269","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":"VE/VCO2 at ventilatory threshold and peak VO2 in CPET studies of patients with scleroderma-associated PAH: A systematic review and meta-analyses","authors":"Julie Better ,&nbsp;Sylvie Leroy ,&nbsp;Maarten K. Ninaber ,&nbsp;Georgia Trakada ,&nbsp;Bilge Kesikburun ,&nbsp;Stephan Rosenkranz ,&nbsp;Ralph Ewert ,&nbsp;Dirk Habedank ,&nbsp;Daniel Dumitrescu ,&nbsp;Yanis Kouchit ,&nbsp;Nihal Martis","doi":"10.1016/j.autrev.2025.103942","DOIUrl":"10.1016/j.autrev.2025.103942","url":null,"abstract":"<div><h3>Context</h3><div>Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in patients with systemic sclerosis (SSc). Cardiopulmonary exercise testing (CPET) has been studied to detect SSc-associated PAH.</div></div><div><h3>Objectives</h3><div>To evaluate the diagnostic value of the ventilatory equivalent for CO₂ at anaerobic or ventilatory threshold [VE/VCO₂(VeT)] and peak oxygen uptake (peak VO₂) for SSc-associated PAH obtained by CPET.</div></div><div><h3>Methods</h3><div>A systematic database search from 1993 to 2024 and meta-analyses were performed according to PRISMA guidelines to include original studies relating to SSc and CPET reporting VE/VCO₂(VeT) and peak VO₂. The random-effects model was chosen for the meta-analyses studying VE/VCO₂(VeT), indexed and predicted percentage (%pred.) peak VO₂, respectively. Meta-regression was only performed for VE/VCO₂(VeT) with covariates defined as the percentage of limited cutaneous disease, percentage of interstitial lung disease, and %pred. of peak VO₂.</div></div><div><h3>Results</h3><div>Out of 206 studies, 941 SSc patients from 15 studies were included. VE/VCO₂(VeT) (11 studies, <em>n</em> = 850) was statistically lower in patients without PAH (32.68 ± 5.42 vs. 39.81 ± 9.32) with a mean effect size of −1.182 (95 %CI, −1.691 to −0.672; <em>p</em> &lt; 0.001) (I² = 86 %). The mean effect size for weight-indexed peak VO₂ (11 studies, <em>n</em> = 848) was 0.713 (95 %CI, 0.371 to 1.054; <em>p</em> &lt; 0.001) with higher values in patients without PAH (16.47 ± 4.62 vs. 13.61 ± 4.16 mL/kg/mn) (I² = 70 %). Similarly, the mean effect size for %pred. Peak VO₂ (12 studies, <em>n</em> = 850) was 0.659 (95 %CI, 0.425 to 0.894; p &lt; 0.001) reflecting higher values in patients without PAH (74.00 ± 17.50 vs. 54.84 ± 18.14 %pred.) (I² = 37 %). Meta-regression analysis of data from 7 studies did not yield significant <em>p</em> values for the covariates.</div></div><div><h3>Conclusions</h3><div>The effect size of each meta-analysis indicates that higher VE/VCO₂(VeT) and lower peak VO₂ may be considered as independent CPET markers of PAH in patients with SSc. CPET is a non-invasive and safe procedure for exploring dyspnoea in patients with SSc and, in association with conventional imaging techniques, may provide a reliable assessment of the presence of PAH.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103942"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353381","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":"MTHFR polymorphisms in autoimmune diseases: Mechanistic and clinical perspectives","authors":"Ting Sun ,&nbsp;Yuxian Wu ,&nbsp;Lingyun Kong ,&nbsp;Jingtong Wang ,&nbsp;Feng Zhang ,&nbsp;Yang Liu ,&nbsp;Jie Gao ,&nbsp;Yaoyang Liu","doi":"10.1016/j.autrev.2025.103939","DOIUrl":"10.1016/j.autrev.2025.103939","url":null,"abstract":"<div><div>The methylenetetrahydrofolate reductase (<em>MTHFR</em>) gene encodes a crucial enzyme in folate metabolism, serving as a central regulator of homocysteine homeostasis and one‑carbon metabolic pathways. This review synthesizes current evidence on the mechanistic and clinical implications of two common <em>MTHFR</em> polymorphisms, C677T and A1298C, in autoimmune pathogenesis. We critically examine their contributions to inflammatory responses, endothelial dysfunction, immune imbalance, and epigenetic modifications. Furthermore, we analyze population-specific associations between these variants and susceptibility to eight autoimmune disorders, genotype-phenotype correlations related to clinical manifestations and comorbidities, as well as pharmacogenomic interactions influencing response to methotrexate therapy. By integrating genetic, molecular, and clinical insights, this review highlights the translational potential of <em>MTHFR</em> genotyping for improving risk stratification and personalized treatment strategies in autoimmune and immune-mediated inflammatory conditions.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"25 1","pages":"Article 103939"},"PeriodicalIF":8.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285537","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":"2025-12-18","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":"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":"2025-12-18","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":"2025-12-18","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}