Autoimmunity Reviews[JOURNAL]
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200 papers
Impact of GLP-1 analogues on immune-mediated inflammatory diseases: A systematic review.
Birda CL, Ibrahim F, Chatterjee A … +3 more , Jena A, Sharma V, Sebastian S
Autoimmun Rev · 2026 Jan · PMID 41077375 · Publisher ↗
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP1RA) are believed to have anti-inflammatory properties apart from antidiabetic and anti-obesity effects. METHODS: We performed a systematic review to evaluate the...
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP1RA) are believed to have anti-inflammatory properties apart from antidiabetic and anti-obesity effects. METHODS: 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. RESULTS: 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). CONCLUSION: GLP1RA use is associated with better disease activity and metabolic outcomes in patients with IMIDs and concomitant metabolic disorders. REGISTRATION: https://osf.io/jvmz6.
Rituximab in glomerular diseases: Indications, long-term use, complications and research gaps.
Gameiro J, Windpessl M, Domingues P … +1 more , Kronbichler A
Autoimmun Rev · 2026 Jan · PMID 41072885 · Publisher ↗
Rituximab (RTX) is a monoclonal antibody targeted against the B-cell surface antigen CD20 that plays a significant role in the treatment of glomerular diseases. It is approved for the induction and maintenance of remissi...
Rituximab (RTX) is a monoclonal antibody targeted against the B-cell surface antigen CD20 that plays a significant role in the treatment of glomerular diseases. It is approved for the induction and maintenance of remission of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and it is used as off-label treatment in several other diseases. Despite the increased use, there is a lack of high-quality evidence for some indications. More specifically, the optimal initial dosing and subsequent frequency of administration, if even indicated, remain to be established. There are short and long-term risks associated with its use, including serious infectious complications, late-onset neutropenia, sustained B-cell depletion, hypogammaglobulinemia, and impaired response to vaccines. In this review, we aimed to summarize the indications for RTX use in the management of glomerular diseases, addressed the potential risks of this treatment, and highlighted some knowledge gaps which are unlikely to be answered in future clinical trials. While newer B-cell targeting therapies, including CD20-depleting antibodies, are tested and might be more effective or approved based on randomized controlled trials, RTX will remain relevant due to the limited costs to healthcare providers, the good safety profile and the long-standing experience of glomerular disease physician to use it.
Adjusting fragility metrics for unequal trial randomizations.
Heston TF
Autoimmun Rev · 2025 Dec · PMID 40972801 · Publisher ↗
Abstract loading — click title to view on PubMed.
The effect of Sphingosine-1-phosphate receptor modulator treatment on leukocyte subsets across different clinical indications: A systematic review.
Nikolakis D, Teichert C, Grootjans J … +2 more , van de Sande MGH, D'Haens GR
Autoimmun Rev · 2025 Dec · PMID 40939814 · Publisher ↗
BACKGROUND: 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 leuko...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Exploring therapeutic potential of Cannabis based therapy in autoimmune and rheumatic disorders.
Michaeli I, Lassman S, Halpert G … +2 more , Jacob G, Amital H
Autoimmun Rev · 2025 Dec · PMID 40907777 · Publisher ↗
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. Despite this growing int...
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. 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. 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. 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.
Calcium signaling dysregulation in rheumatoid arthritis: a comparative perspective with osteoarthritis.
Nguyen TD, Abreu H, Tommasi N … +7 more , Azzarone L, Di Martino RMC, Riva B, Raineri D, Pirali T, Chiocchetti A, Cappellano G
Autoimmun Rev · 2025 Dec · PMID 40885506 · Publisher ↗
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, eme...
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.
Animal models for connective tissue disease-associated interstitial lung disease: Current status and future directions.
Tang Z, Yang H, Liang X … +4 more , Chen J, He Q, Zhu D, Liu Y
Autoimmun Rev · 2025 Dec · PMID 40865895 · Publisher ↗
Interstitial lung disease (ILD) significantly contributes to connective tissue disease (CTD) mortality. Although guidelines for managing CTD-associated ILD (CTD-ILD) exist, many patients respond poorly to treatment owing...
Interstitial lung disease (ILD) significantly contributes to connective tissue disease (CTD) mortality. Although guidelines for managing CTD-associated ILD (CTD-ILD) exist, many patients respond poorly to treatment owing to two key factors: (1) incomplete understanding of subtype-specific pathogenic mechanisms, and (2) reliance on therapies adapted from systemic sclerosis or nonpulmonary rheumatic diseases, which fail to address the unique pathophysiology of distinct CTD-ILD subtypes. This hinders personalized treatment and underscores the need for robust preclinical models that accurately replicate disease-specific mechanisms. However, challenges remain: (1) the lack of models that fully capture the heterogeneity of these disorders and (2) the absence of systematic structured reviews to guide model selection, despite recent advancements in experimental methodologies. These issues often result in mismatches between research goals and model utility. This review summarizes current CTD-ILD animal models, focusing on their construction, characteristics, and limitations, and highlighting differences between each model and the corresponding human disease. We summarize these disparities and propose emerging technologies, including CRISPR/Cas9-mediated genome editing, humanized mice, and lung organoids/lung-on-a-chip systems, that may facilitate the development of next-generation models. By integrating established and emerging strategies, we aim to provide guidance for model selection and development, promote precision modeling, accelerate targeted therapy discovery, and ultimately improve clinical outcomes. We emphasize the importance of developing subtype-specific models to avoid a "one-model-fits-all" approach.
Systemic lupus erythematosus and the gut microbiome: To look forward is to look within - A systematic review and narrative synthesis.
Guimarães de Oliveira D, Machado A, Lacerda PC … +2 more , Karakikla-Mitsakou Z, Vasconcelos C
Autoimmun Rev · 2025 Dec · PMID 40876561 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: SLE patients exhibit gut microbiome dysbiosis, with reduced microbial richness and altered bacterial taxa. A lower Firmicutes/Bacteroidetes ratio is frequently observed. Enrichment of specific taxa, such as Enterococcus, Lactobacillus, and Ruminococcus gnavus, 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. CONCLUSIONS: 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.
The roles of S100A8/A9 and S100A12 in autoimmune diseases: Mechanisms, biomarkers, and therapeutic potential.
Wang X, Luo Y, Zhou Q … +1 more , Ma J
Autoimmun Rev · 2025 Dec · PMID 40876560 · Publisher ↗
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...
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.
Hedgehog signaling pathway: A research review on a new therapeutic target for rheumatoid arthritis.
Yan Y, Sun C, Hoang MH … +2 more , Wang X, Gao Y
Autoimmun Rev · 2025 Dec · PMID 40876559 · Publisher ↗
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, abnorm...
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.
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.
Fassio A, Sebastiani M, Pollastri F … +10 more , Cozzini F, Crotti C, Ughi N, De Lorenzis E, Mancuso S, Radin M, Carrara G, Landolfi G, Rozza D, Manfredi A
Autoimmun Rev · 2025 Dec · PMID 40876558 · Publisher ↗
BACKGROUND: 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 sp...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
The fragility of randomized controlled trials in large vessel vasculitis.
Misra DP, Mukhtyar CB, Chandwar K … +2 more , Putman M, Walsh M
Autoimmun Rev · 2025 Dec · PMID 40865894 · Publisher ↗
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 comprehe...
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, n = 14; TAK, n = 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.
Artificial intelligence for biopsies and imaging modalities in systemic autoimmune rheumatic diseases: An instructive narrative review.
Panagiotopoulos KN, Tsiknakis N, Zaridis DI … +3 more , Tzioufas AG, Fotiadis DI, Goules AV
Autoimmun Rev · 2025 Dec · PMID 40865893 · Publisher ↗
PURPOSE: 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 re...
PURPOSE: 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. RESULTS: 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. CONCLUSIONS: 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.
In search of biomarkers for prediction of drug treatment responses in rheumatoid arthritis: Lessons learned and future perspectives.
Dara A, Vlachogiannis NI, Fragoulis GE … +2 more , Tektonidou MG, Sfikakis PP
Autoimmun Rev · 2025 Dec · PMID 40846294 · Publisher ↗
Prompt initiation of effective drug treatment is crucial for controlling inflammation and preventing disease progression in rheumatoid arthritis, the most prevalent systemic rheumatic disease. The growing range of drug t...
Prompt initiation of effective drug treatment is crucial for controlling inflammation and preventing disease progression in rheumatoid arthritis, the most prevalent systemic rheumatic disease. The growing range of drug therapies over the past three decades and the fact that only a minority of patients achieve sustained long-term remission with any given therapy, make imperative the need for biomarkers predicting responses to specific drugs. Moreover, promising therapeutic approaches under development, namely cellular therapies, could be promptly applicable at earlier disease stages in about 10-15 % of RA patients who will be refractory to all approved drugs. In this scoping review of original articles published until 25th of July 2025, we present a critical overview of the literature pertaining to the prognostic value of blood immunophenotyping, circulating proteins and blood proteomics, transcriptomics, metabolomics and lipidomics, as well as of endogenous cortisol production and synovial histopathology. We also discuss the emerging use of artificial intelligence-based approaches for developing response prediction models that integrate clinical features with molecular profiling. We conclude that current knowledge does not allow to discern future responders to methotrexate and/or to different biologic agents from non-responders because established biomarkers to identify those patients who will benefit the most from each therapeutic option are lacking. We also emphasize the lack of standardized research approaches to discover biomarkers predicting drug treatment responses and try to identify the relevant pitfalls and describe the lessons learned over the years. Finally, we propose a roadmap and the application of advanced analytical and machine learning techniques for future research in this area.
Systemic sclerosis and AHR: Shedding light on a hidden connections.
Wajda A, Paradowska-Gorycka A, Esser C
Autoimmun Rev · 2025 Dec · PMID 40840815 · Publisher ↗
Systemic sclerosis (SSc) is a complex and debilitating autoimmune disease marked by fibrosis of the skin and inner organs, alongside chronic inflammation, and vascular abnormalities. SSc pathogenesis involves both geneti...
Systemic sclerosis (SSc) is a complex and debilitating autoimmune disease marked by fibrosis of the skin and inner organs, alongside chronic inflammation, and vascular abnormalities. SSc pathogenesis involves both genetic and environmental factors, such as silica dust or benzene exposure but the underlying molecular mechanisms regulating fibrogenesis and organ involvement are not fully understood. In part due to this knowledge gap, treatment options are limited. In this review we look at the possible role of the aryl hydrocarbon receptor (AHR), a transcription factor involved in immunomodulation, fibrosis and drug metabolism and inflammatory responses, especially in barrier organs. AHR activation by binding to one of its many small molecular weight ligands can result in gene-expression changes in the nucleus (its role as a transcription factor) but also lead to knock-on effects on other signaling pathways via direct binding (e.g., to NFkB) or via AHR's protein degradation capacity (E3 ligase). In some cell types transcription target genes include the fibrogenic cytokine TGF-β or metalloproteinases responsible for extracellular matrix remodeling. AHR has been shown to be highly expressed in all cutaneous cell populations, and to be critical for skin homeostasis. Given its context-dependent effects, AHR may act as both a pro- and anti-fibrotic regulator in SSc, depending on ligand availability and cellular environment. This dual role highlights AHR as a potential therapeutic target, where selective agonists or antagonists could help restore immune and fibrotic homeostasis. Here, we explore these mechanisms and discuss the potential of AHR as a therapeutic target for modulating disease progression and improving patient outcomes.
Rapid radiographic progression in rheumatoid arthritis: Definition, prediction and treatment.
Lv B, Li F, Hu F … +1 more , Xu L
Autoimmun Rev · 2025 Sep · PMID 40829710 · Publisher ↗
Rapid radiographic progression (RRP) in rheumatoid arthritis (RA) is strongly correlated with unfavorable long-term prognostic outcomes. Early identification of RRP is paramount, as prompt intervention and the implementa...
Rapid radiographic progression (RRP) in rheumatoid arthritis (RA) is strongly correlated with unfavorable long-term prognostic outcomes. Early identification of RRP is paramount, as prompt intervention and the implementation of intensified therapeutic regimens have the potential to substantially improve clinical outcomes. This review summarized the different definitions and current key predictors of RRP, such as genetic predispositions, body mass index and so on. Furthermore, the existing matrix-based predictive models for RRP were compared. In addition, the potential treatment options for patients with RRP were also outlined. The objective of this review is to improve the early detection of RRP, thereby facilitating timely intervention and the adoption of personalized treatment paradigms that optimize patient prognosis.
Systemic lupus erythematosus in critical care: A systematic review of ICU outcomes and management.
Ramírez-Lara E, Mendoza-Pinto C, Munguía-Realpozo P … +5 more , Saavedra-Salinas MÁ, Etchegaray-Morales I, Ayón-Aguilar J, Montiel-Jarquín ÁJ, Martínez-Méndez S
Autoimmun Rev · 2025 Dec · PMID 40829709 · Publisher ↗
BACKGROUND: Systemic lupus erythematosus (SLE) often progresses to critical illness requiring intensive care unit (ICU) admission, yet contemporary data on outcomes, prognostic factors, and therapeutic approaches are sca...
BACKGROUND: Systemic lupus erythematosus (SLE) often progresses to critical illness requiring intensive care unit (ICU) admission, yet contemporary data on outcomes, prognostic factors, and therapeutic approaches are scattered. OBJECTIVE: To synthesize recent evidence on causes of ICU admission, mortality predictors, and management strategies in adult SLE. METHODS: A PRISMA-compliant search of PubMed, Web of Science and Cochrane Library (inception-31 December 2024) retrieved studies enrolling adults (≥18 years) with confirmed SLE treated in ICUs. Two reviewers independently selected articles and extracted data; methodological heterogeneity precluded meta-analysis, so results were narratively synthesized. RESULTS: Thirty-nine studies met the criteria. Infection (40 %), pulmonary involvement (17 %) and renal flares (13 %) were the most common admission triggers. Reported ICU mortality ranged from 20 % to 82 % but rose sharply when baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) exceeded 16, approximating 80 % mortality (sensitivity 84 %, specificity 90 %) and outperforming Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) in discriminating survivors. Additional independent predictors were APACHE II > 16, need for mechanical ventilation, renal replacement therapy and vasopressor support. Mechanical ventilation (59 %) and vasoactive agents (39 %) were the predominant ICU interventions. Immunomodulatory management was heterogeneous: high-dose corticosteroids and cyclophosphamide were ubiquitous, whereas mycophenolate, antimalarials, intravenous immunoglobulin, plasmapheresis, and extracorporeal membrane oxygenation were reserved for selected scenarios. CONCLUSIONS: Early recognition of poor prognostic factors and prompt ICU admission are essential to improving outcomes in SLE.
Gut microbiota in rheumatoid arthritis: Mechanistic insights, clinical biomarkers, and translational perspectives.
Qi XY, Liu MX, Jiang XJ … +7 more , Gao T, Xu GQ, Zhang HY, Su QY, Du Y, Luo J, Zhang SX
Autoimmun Rev · 2025 Dec · PMID 40825448 · Publisher ↗
Rheumatoid arthritis (RA) is a systemic autoimmune disease shaped by complex interactions between genetics and environmental factors, among which gut microbiota has emerged as a critical modulator. Recent advances have i...
Rheumatoid arthritis (RA) is a systemic autoimmune disease shaped by complex interactions between genetics and environmental factors, among which gut microbiota has emerged as a critical modulator. Recent advances have implicated gut microbiota dysbiosis in RA pathophysiology, with evidence spanning mechanistic, diagnostic, and therapeutic dimensions. This review summarizes current knowledge of the gut-joint axis and outlines microbiota-based strategies for RA management. Numerous studies have demonstrated consistent alterations in gut microbial communities in patients with RA, with enrichment of Prevotella copri observed in 75% of patients with new-onset RA compared to 21.4% of healthy controls, suggesting a potential association with disease initiation. Mechanistically, we detail how microbial dysbiosis, including that of bacteria, fungi, and viruses, disrupts intestinal barrier integrity, skews T helper 17/T regulatory and T follicular helper/T follicular regulatory immune axes, induces molecular mimicry, and alters the profiles of microbial metabolites such as short-chain fatty acids. Diagnostically, microbial taxa and metabolites serve as promising biomarkers. Machine learning models based on microbiota profiles have achieved area under the curve (AUC) values exceeding 0.88, with discriminatory taxa such as Ruminococcus gnavus and Fusicatenibacter. Therapeutically, we reviewed microbiota-targeted interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, diet, and herbal medicines, highlighting the emerging field of pharmacomicrobiomics. Gut microbial signatures have shown promise in predicting treatment responses, including methotrexate efficacy via the enterotype-based gut microbial human index model (AUC = 0.945). This review proposes an integrated framework linking microbial alterations with RA onset and progression and presents gut microbiota as a promising frontier for biomarker discovery, personalized intervention, and precision medicine.
The role of mTOR signaling pathway in systemic lupus erythematosus and systemic vasculitis.
Michailidou D, Gartshteyn Y, Askanase AD … +1 more , Perl A
Autoimmun Rev · 2025 Nov · PMID 40812528 · Publisher ↗
The mechanistic target of rapamycin (mTOR) is a central regulator of cellular proliferation, metabolism, survival and growth. The mTOR pathway consists of two protein complexes, mTORC1 and mTORC2, which have different se...
The mechanistic target of rapamycin (mTOR) is a central regulator of cellular proliferation, metabolism, survival and growth. The mTOR pathway consists of two protein complexes, mTORC1 and mTORC2, which have different sensitivities to rapamycin and cellular functions. mTOR regulates autophagy as well as the function and/or differentiation of many immune cells, including T cells, dendritic cells, natural killer cells, macrophages, neutrophils, and B cells. mTOR signaling is implicated in the pathogenesis of cancer, diabetes and several autoimmune diseases. In this review, we summarize how mTOR pathway may contribute to the pathogenesis of systemic lupus erythematosus (SLE) and systemic vasculitis. In SLE, mTOR activation induces activation of CD4 + T cells, skews differentiation towards Th17 cells resulting in Th17/Treg imbalance, increases production of IL-4 in CD4 - CD8- double-negative (DN) T cells, reduces the number of circulating CD8 memory T cells, promotes B-cell proliferation, increases production of plasmacytes and secretion of autoantibodies, as well as activation of myeloid dendritic cells. In large vessel vasculitis, mTOR overactivity promotes endothelial cell growth, T cell differentiation towards Th1 and Th17 polarization, impairment of Tregs and activation of smooth muscle cell-derived myofibroblasts that contribute to arterial stenosis and ischemia, whereas in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, reduced activity of the mTOR signaling pathway is observed in neutrophils isolated during the active phase of the disease. Targeting mTOR pathway with rapamycin, rapalogues, or other mTOR inhibitors could be efficacious in the treatment of these complex autoimmune diseases.
The role of sleep in multiple sclerosis.
Cordone S, Alfonsi V, De Gennaro L
Autoimmun Rev · 2025 Nov · PMID 40774353 · Publisher ↗
Multiple Sclerosis (MS) is an autoimmunity-related disorder that mainly affects young adults. The high prevalence of the disease and its impact on patients' quality of life led researchers to investigate the etiopathogen...
Multiple Sclerosis (MS) is an autoimmunity-related disorder that mainly affects young adults. The high prevalence of the disease and its impact on patients' quality of life led researchers to investigate the etiopathogenesis of the disease to identify possible modifiable factors and consequent effective intervention strategies. Recent hypotheses suggest that the etiopathogenesis of MS is multifactorial and includes factors related to the immune system, neuroinflammation and neurodegeneration. In this scenario, sleep seems to have a close indirect relationship with MS, through its relationship with each of those factors and given the high incidence of sleep disorders in the MS population. Furthermore, given the growing interest of research in the mechanisms underlying MS and therapies able to alleviate MS-related symptoms at all stages of the disease, a more in-depth study of the role of sleep and its loss and disturbances and the factors intrinsically related to sleep and MS could be useful both to investigate the etiopathogenetic factors of MS and to develop non-invasive intervention strategies for MS treatment.
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