Autoimmunity Reviews[JOURNAL]
Sun
200 papers
VEXAS syndrome in adults: A narrative review of genomic pathogenesis, multisystem phenotypes, diagnostic algorithms, and emerging therapeutic strategies.
Vitale A, Cifuentes-González C, Gentile M … +5 more , Cataldi G, Agrawal K, Agrawal R, Conforti A, Cantarini L
Autoimmun Rev · 2026 May · PMID 41871819 · Publisher ↗
AIM: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently defined adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene. This narrative review synthesizes c...
AIM: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently defined adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene. This narrative review synthesizes current insights into its epidemiology, pathogenesis, clinical spectrum, diagnostic strategies, and emerging therapeutic approaches, emphasizing data from the French and AIDA registries. METHOD: We conducted a comprehensive literature search of PubMed, Scopus, and Web of Science databases up to 15 June 2025, using keywords including "VEXAS", "UBA1", "autoinflammatory syndromes", "myelodysplastic syndromes", and "JAK inhibitors". Studies reporting epidemiological data, clinical phenotypes, pathophysiological mechanisms, diagnostic pathways, or therapeutic outcomes were included. Case reports and non-English articles without abstracts were excluded. DISCUSSION: Since its identification in 2020, more than 300 VEXAS cases have been reported, primarily affecting older males. The clinical phenotypes include relapsing polychondritis, cytopenias, neutrophilic dermatoses, and frequent overlap with myelodysplastic syndromes. Diagnosis is confirmed by detecting somatic mutation in UBA1, most commonly at codon 41. Treatment responses are heterogeneous: corticosteroids are often used initially,but longer-lasting benefits are observed with JAK inhibitors, hypomethylating agents, or hematopoietic stem-cell transplantation. However, therapeutic decision-making remains empirical mainly due to the lack of controlled trials. CONCLUSION: VEXAS syndrome exemplifies the interface between clonal hematopoiesis and systemic inflammation. Early molecular diagnosis and genotype-informed treatment strategies are critical. Collaborative, prospective studies are urgently needed to refine diagnostic algorithms and optimize therapeutic outcomes.
Autoimmunity, diet and autophagy.
Blaise S, Muller S
Autoimmun Rev · 2026 May · PMID 41865949 · Publisher ↗
Autophagy is a highly conserved lysosomal recycling pathway that couples nutrient availability to cellular quality control and immune regulation. Accumulating evidence identifies autophagy as a central mechanistic interf...
Autophagy is a highly conserved lysosomal recycling pathway that couples nutrient availability to cellular quality control and immune regulation. Accumulating evidence identifies autophagy as a central mechanistic interface through which dietary exposures influence metabolic inflammation and the maintenance or breakdown of immune tolerance in autoimmune diseases. This review synthesizes current molecular and cellular insights into how nutrition modulates autoimmune susceptibility and disease activity by shaping autophagic pathways across immune and metabolic tissues. Dietary signals exert bidirectional and context-dependent effects on immune homeostasis. Deficiencies in key micronutrients, including vitamin D, zinc, selenium, and omega-3 fatty acids, can impair regulatory immune circuits and promote pro-inflammatory cytokine profiles. Conversely, overnutrition, obesity, and Westernized dietary patterns drive chronic low-grade inflammation, compromise epithelial barrier integrity, and remodel the gut microbiota, thereby amplifying systemic immune activation and autoantibody-related pathways. The review describes major autophagy programs and highlights their roles in lymphocyte survival and memory, antigen presentation, and cytokine regulation. Genetic and experimental evidences indicate that defective autophagy and lysosomal dysfunction can alter antigen handling and perpetuate pathological immune activation. Nutritional regulation of autophagy is discussed through nutrient-sensing pathways, particularly mechanistic target of rapamycin complex 1, AMP-activated protein kinase, and sirtuin 1. Fasting-based strategies and time-restricted eating may enhance autophagic competence, whereas high-glycemic, obesogenic diets can suppress autophagy and intensify oxidative and endoplasmic reticulum stress. Finally, a precision immunonutrition framework is proposed that integrates genetic susceptibility, microbiota features, metabolic profiling, and autophagy biomarkers to guide individualized, adjunctive interventions in autoimmune diseases.
Chinese recommendations for the diagnosis and management of non-radiographic axial spondyloarthritis.
Dai SM, Xu H, Zhao Y … +1 more , Committee for “Guidelines for the Diagnosis and Treatment of Non-Radiographic Axial Spondyloarthritis”, Chinese Rheumatology Association, Committee for Rheumatologists and Immunologists of Chinese Primary Health Care Foundation
Autoimmun Rev · 2026 May · PMID 41865948 · Publisher ↗
BACKGROUND: The term of non-radiographic axial spondyloarthritis (nr-axSpA) has stimulated a number of practice-changing developments, but the meaning of nr-axSpA has not been well understood by clinicians, including rhe...
BACKGROUND: The term of non-radiographic axial spondyloarthritis (nr-axSpA) has stimulated a number of practice-changing developments, but the meaning of nr-axSpA has not been well understood by clinicians, including rheumatologists. The diagnosis of nr-axSpA remains clinically problematic, with substantial risks of overdiagnosis. OBJECTIVE: To generate a set of evidence-based recommendations for the diagnosis and management of patients with nr-axSpA for physicians, health professionals, and rheumatologists. METHODS: The recommendations were developed through a Delphi method prioritizing 37 key clinical questions. Evidence Synthesis Group performed systematic literature searches and evidence evaluation. In task force meetings, the evidence was presented and discussed, resulting in formulation and updating of overarching principles and recommendations that were subsequently voted on by an Expert Panel. RESULTS: Six overarching principles and 17 recommendations were agreed. The principles focus on differential diagnosis, treatment target, monitoring and re-assessment. The recommendations deal with: Definitions of axSpA and nr-axSpA (#1-2); The value of MRI and CT in diagnosis (#3-7); The specificity of the ASAS-axSpA classification criteria, the long-term outcome and risk factors of progressing to AS (#8-9); Non-pharmacological management and NSAIDs treatment (#10-11); The indication of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) for patients with or without specific comorbidities(#12-14); Switching to another bDMARD or JAKi in primary failure and secondary failure (#15-16); Tapering of a bDMARD in sustained remission (#17). CONCLUSIONS: The recommendations represent the first effort to establish a clear definition of axSpA, to critically evaluate the imaging clues in and performance of the classification criteria for diagnosing nr-axSpA, and to provide specific guidance for nr-axSpA management.
The effect of Nintedanib on KL-6 levels in patients with interstitial lung disease: A systematic review and meta-analysis.
Boutel M, Skouvaklidou E, Partalidou S … +5 more , Boutou A, Antoniou KM, Katsigianni I, Adamichou C, Dimitroulas T
Autoimmun Rev · 2026 Apr · PMID 41864310 · Publisher ↗
BACKGROUND: Interstitial Lung Diseases (ILDs) are pulmonary disorders with high levels of morbidity and mortality. Anti-fibrotic treatment halts ILD progression. Krebs von den Lungen-6 (KL-6) is a circulating glycoprotei...
BACKGROUND: Interstitial Lung Diseases (ILDs) are pulmonary disorders with high levels of morbidity and mortality. Anti-fibrotic treatment halts ILD progression. Krebs von den Lungen-6 (KL-6) is a circulating glycoprotein released from damaged alveolar epithelium and is considered a promising biomarker for disease activity and prognosis in ILDs. However, its role in monitoring response to anti-fibrotic therapy, particularly nintedanib, remains uncertain. METHODS: Following PRISMA (PROSPERO CRD420251030451), we searched PubMed, Cochrane CENTRAL, and Scopus to June 2025 for studies of ILD patients on nintedanib or pirfenidone ≥6 months reporting pre/post-KL-6. Standardized mean change (SMC) was pooled with random-effects models; heterogeneity (I, τ) and exploratory meta-regression were assessed. RESULTS: Thirteen studies (n = 732) met the inclusion criteria; five contributed to the meta-analysis. Nintedanib (4 studies) showed no significant change in KL-6 (SMC 0.30, 95% CI -0.12 to 0.71; p = 0.16), with high heterogeneity (I = 81.8%). Excluding one outlier attenuated the effect (SMC 0.08, 95% CI -0.13 to 0.28) and reduced heterogeneity (I = 25.9%). Across five antifibrotic studies, the results were likewise null (SMC 0.20, 95% CI -0.12 to 0.52; p = 0.21). Meta-regression analysis suggested a greater reduction in KL-6 with lower baseline FVC (β = -0.018; p = 0.096), accounting for ∼31% of the between-study variance. CONCLUSIONS: Anti-fibrotic therapy appears to stabilize KL-6 in ILD, supporting its prognostic utility. Baseline lung function may influence the KL-6 response. Larger, standardized prospective studies are needed to clarify KL-6's role as a dynamic biomarker of treatment response in ILD.
Angiogenic imbalance and endothelial dysfunction in the placenta in antiphospholipid syndrome.
Martirosyan A, Kriegova E, Manukyan G
Autoimmun Rev · 2026 Apr · PMID 41846027 · Publisher ↗
Placental vascular development depends on the tightly orchestrated interplay of vasculogenesis, angiogenesis, and vascular remodeling to sustain efficient maternal-fetal exchange across gestation. In obstetric antiphosph...
Placental vascular development depends on the tightly orchestrated interplay of vasculogenesis, angiogenesis, and vascular remodeling to sustain efficient maternal-fetal exchange across gestation. In obstetric antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) function as active pathogenic mediators that perturb this program by promoting endothelial activation, immune-driven injury, and a shift toward angiogenic imbalance. This review summarizes the fundamental mechanisms governing normal placental vascular development, emphasizing the coordinated roles of uterine immune cells and extravillous trophoblasts. Accumulating evidence indicates that aPL-β2GPI interactions promote NF-κB-dependent inflammatory and prothrombotic endothelial responses, accompanied by complement and inflammasome activation, oxidative stress, and NET-associated vascular injury. At the clinical level, pregnancies complicated by APS frequently display a preeclampsia-like anti-angiogenic profile, characterized by elevated sFlt-1, reduced PlGF, and increased sFlt-1/PlGF ratios, which often precede clinical manifestations and associate with placental insufficiency, fetal growth restriction, and pregnancy loss.
Targeting autoimmunity: Phosphodiesterase inhibitors as immunomodulators-a review of current insights and future direction.
Bazsó A, Szodoray P, Shoenfeld Y … +2 more , Nagy G, Kiss E
Autoimmun Rev · 2026 Apr · PMID 41839428 · Publisher ↗
Phosphodiesterase (PDE) inhibitors are a class of pharmacological agents that regulate immune and vascular function by controlling the intracellular concentration of key second messengers. By modulating cyclic nucleotide...
Phosphodiesterase (PDE) inhibitors are a class of pharmacological agents that regulate immune and vascular function by controlling the intracellular concentration of key second messengers. By modulating cyclic nucleotide signaling, particularly cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), PDE inhibitors exert pleiotropic effects on vascular tone, immune cell activation, and fibrotic remodeling. Dysregulation of cAMP- and cGMP-dependent pathways contributes to endothelial dysfunction, chronic inflammation, and tissue remodeling in autoimmune, fibrotic, and neurodegenerative diseases. In rheumatology, PDE3, PDE4, and PDE5 isoforms are of particular translational relevance. PDE3 inhibitors improve vasodilation and platelet regulation; PDE5 inhibitors enhance endothelial NO-cGMP signaling and are clinically established in pulmonary arterial hypertension and digital vasculopathy; while PDE4 inhibition suppresses cytokine-driven immune activation by reducing the production of pro-inflammatory mediators, contributing to therapeutic efficacy in conditions such as psoriasis, psoriatic arthritis, and connective tissue disease-associated interstitial lung disease (CTD-ILD). Emerging PDE-targeted agents, including ibudilast and the PDE4B-selective inhibitor nerandomilast, combine immunomodulatory and antifibrotic properties. These compounds have demonstrated clinical benefit and improved tolerability in patients with progressive fibrotic lung disease, highlighting the therapeutic potential of isoform-selective PDE inhibition. Collectively, targeting the NO-cGMP-cAMP signaling axis provides a unifying mechanistic framework for the treatment of vascular, immune, and fibrotic manifestations of rheumatic disease, positioning PDE inhibition as an emerging pillar of modern translational rheumatology.
Pathogenic mechanisms of action of autoantibody-mediated central nervous system disorders targeting neuroglial surface antigens.
Lerch M, Irani SR, Ramanathan S
Autoimmun Rev · 2026 Apr · PMID 41831629 · Publisher ↗
Autoantibody-mediated diseases targeting central nervous system antigens are increasingly recognised and may manifest as encephalitis or demyelination. A subset of these diseases can be associated with autoantibodies tar...
Autoantibody-mediated diseases targeting central nervous system antigens are increasingly recognised and may manifest as encephalitis or demyelination. A subset of these diseases can be associated with autoantibodies targeting neuronal or glial cell surface proteins (neuroglial surface antibodies or NGsAbs), including leucine-rich glioma inactivated 1, contactin-associated protein-like 2, the N-methyl-D-aspartate receptor, aquaporin-4, and myelin oligodendrocyte glycoprotein, among others. There is accumulating evidence that many NGsAbs may be directly pathogenic, and the associated diseases are responsive to immunotherapy. Underlying disease pathogenesis is still not fully determined and NGsAbs can demonstrate multiple effector mechanisms. In this review, we will briefly outline the clinical syndromes associated with NGsAbs, followed by a detailed breakdown of known in vitro, in vivo and ex vivo studies elucidating pathogenic mechanisms of these autoantibodies. Our understanding of the underlying immunobiology of these conditions will ultimately inform more refined therapeutic approaches.
Immune rehabilitation after renal transplantation in autoimmune diseases: Balancing immunosuppression and risk of complications.
Alnaimat F, AbuHelal A, Elmusa R … +4 more , Naimat R, Yurikova O, Umbetzhanov R, Zimba O
Autoimmun Rev · 2026 Apr · PMID 41825680 · Publisher ↗
Autoimmune kidney diseases represent a major etiology of chronic kidney disease and often result in end-stage kidney disease (ESKD), in which renal transplantation offers better survival and quality of life as compared t...
Autoimmune kidney diseases represent a major etiology of chronic kidney disease and often result in end-stage kidney disease (ESKD), in which renal transplantation offers better survival and quality of life as compared to extended dialysis. However, patients with autoimmune kidney diseases face certain post-transplantation complications, such as the recurrence of the disease, infection, malignancy, and immune dysregulation, which can be explained by the fact that such patients are immunosuppressed for life. This review discusses the immunopathogenesis of the autoimmune kidney diseases: lupus nephritis, antineutrophil cytoplasmic antibody-associated vasculitis, systemic sclerosis-related renal disease, membranous nephropathy, and IgA nephropathy, and their effects on transplant outcomes. Disease recurrence, graft survival, and systemic complications in transplantation and disease-specific predictors and risk factors in relapse will be reviewed. A personalized, biomarker-directed intervention applied in the peri-transplant phase can potentially optimize the long-term graft performance, reduce the relapse, and improve overall outcomes in this high-risk group. Ultimately, priorities of future research, including the need to conduct multidisciplinary clinical trials to optimize the techniques of immune rehabilitation, are highlighted.
Clinical characteristics and cancer risk of anti-OJ antisynthetase syndrome: A cohort comparative study and a systematic literature review.
Pillot V, Toquet S, Charuel JL … +25 more , Tansley S, Boussouar S, Brillet PY, Lu H, Vellas D, Boulahfa ST, Louis SL, Uzunhan Y, Belle A, Cohen P, Ghillani-Dalbin P, Miyara M, Hie M, Foulon G, Gambier N, Boitiaux JF, Fuzibet P, Crestani B, Baudelet L, Ilzkovitz M, Nagant C, Bouvier AM, Jooste V, Benveniste O, Allenbach Y
Autoimmun Rev · 2026 Apr · PMID 41825679 · Publisher ↗
BACKGROUND: Antisynthetase syndrome (ASyS) is a systemic autoimmune disease that primarily affects the lungs, joints, and muscles, and is associated in over 90% of cases with anti-Jo-1, anti-PL7, or anti-PL12 antibodies....
BACKGROUND: Antisynthetase syndrome (ASyS) is a systemic autoimmune disease that primarily affects the lungs, joints, and muscles, and is associated in over 90% of cases with anti-Jo-1, anti-PL7, or anti-PL12 antibodies. ASyS is not associated with malignancy. Anti-OJ autoantibody-positive ASyS is poorly characterized, as it is a rare anti-synthetase antibody and commercial immunoassay kits lack reliability. METHODS: We conducted a retrospective comparative cohort study of anti-OJ patients. Anti-OJ was identified by immunoprecipitation. Clinical, biological, radiological, and myopathological data were collected. ASyS OJ-negative patients positive for anti-Jo-1, anti-PL7, or anti-PL12 antibodies were used as controls. Cancer incidences were compared to the aged and sex matched general population using standardized incidence ratios. A systematic literature review of anti-OJ patients was also conducted for descriptive comparison. RESULTS: Anti-OJ patients (n = 22) were older at diagnosis (69 years [51.5-75], p < 0.01) and exhibited lower frequencies of muscular (54.5%, p < 0.01) and articular involvement (26.7%, p < 0.01) compared OJ-negative ASyS patients (n = 158), while interstitial lung disease remained a prominent feature in both groups. Cancer incidence was markedly increased in the anti-OJ patients (SIR = 3.23 [95% CI: 1.21-8.62]) compared to general population, in contrast to anti-Jo-1 and anti-PL7/12 patients, where no significant difference was observed. The literature review of anti-OJ patients (n = 106) showed consistent results with our cohort. CONCLUSION: Anti-OJ ASyS define a distinct clinical subset within the ASyS spectrum, and a unique increased risk of malignancy. These findings advocate for enhanced malignancy screening and dedicate serological testing in this rare subgroup.
Precision immunotherapies for systemic lupus erythematosus: From pathogenic targets to translational horizons.
Guo C, Lei Z, Zhao L … +1 more , Wei P
Autoimmun Rev · 2026 Apr · PMID 41812738 · Publisher ↗
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder in which aberrant B-cell activation, persistent autoantibody production, and dysregulated cytokine and intracellular signaling networks converge t...
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder in which aberrant B-cell activation, persistent autoantibody production, and dysregulated cytokine and intracellular signaling networks converge to produce relapsing-remitting, multisystem inflammation and cumulative organ damage. Although conventional immunosuppressants remain the backbone of care and can attenuate disease activity, their insufficient specificity, dose-dependent toxicities, and inability to re-establish durable immunologic tolerance limit long-term disease control. Converging advances in human immunology, molecular medicine, and cell engineering are now enabling a paradigm shift toward mechanism-based precision therapies. In this review, we synthesize three interconnected therapeutic domains that collectively architect this transition: (i) selective targeting of immune-cell surface antigens and costimulatory pathways-for example, BAFF/APRIL antagonism and CD19-directed CAR-T strategies that deplete or recalibrate autoreactive B-cell compartments; (ii) modulation of proinflammatory cytokine networks and intracellular signaling cascades-including IFN-I pathway blockade and pharmacologic inhibition of JAK/STAT and mTOR axes-to dampen upstream drivers and nodal amplifiers of lupus immunopathology; and (iii) next-generation, autoantibody-focused approaches-such as mimetic peptides, CAAR-T cells, and antigen-specific Tregs-that aim to confine immune intervention to pathogenic antigenic circuits while minimizing systemic immunosuppression. We further construct a comprehensive clinical implementation roadmap to evaluate the realistic scalability, accessibility, and translational windows of these therapies over the next 5 to 10 years. Crucially, we highlight the emerging role of artificial intelligence (AI) and machine learning in addressing inter-patient heterogeneity-ranging from multi-omic molecular endotyping and predictive therapeutic modeling to the computational design of next-generation antibodies and CARs. Synergizing these mechanistic and strategic breakthroughs may accelerate progress toward mechanism-guided, individualized, and durable disease control and remission in SLE.
Epidemiology of eosinophilic granulomatosis with polyangiitis in northern Spain: A population-based study (2000-2024) and literature review.
Benavides-Villanueva F, Prieto-Peña D, Calvo-Río V … +7 more , Renuncio-García M, Martín-Gutiérrez A, Poo-Fernandez C, Ferraz-Amaro I, Garcia-Rivero JL, Beatriz AB, Blanco R
Autoimmun Rev · 2026 Apr · PMID 41806950 · Publisher ↗
OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis. Epidemiological data remain limited and vary considerably across regions and time periods, partly due to differences in st...
OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis. Epidemiological data remain limited and vary considerably across regions and time periods, partly due to differences in study designs and diagnostic criteria. This study aimed to describe the incidence and prevalence of EGPA in a defined population from northern Spain, according to newly established EGPA classification criteria. METHODS: We conducted an observational study including EGPA cases diagnosed between 2000 and 2024 at a single university hospital. Clinical data were extracted from medical records. EGPA cases were identified using 2022 ACR/EULAR classification criteria. Incidence and prevalence rates calculated using official population data, expressed per 1,000,000 inhabitants per year. RESULTS: Twenty-five patients were included (56% male; mean age at diagnosis: 66 ± 14 years). Pulmonary involvement was the most frequent (88%), followed by ear, nose, and throat (ENT) symptoms (68%). ANCA was positive in 48% of cases, all MPO-ANCA. Mean annual incidence was 2.2 (95% CI: 0.8-3.6) per 10 inhabitants, increasing across three periods: 0.5 (2000-2008), 1.7 (2009-2016), and 5.4 (2017-2024). Prevalence in 2024 reached 59.9 per 10. This rise coincided with the introduction of a multidisciplinary consultation involving rheumatologists and pulmonologists (2015) and the establishment of a dedicated vasculitis clinic (2020), likely improving diagnostic accuracy and centralizing cases otherwise undetected. CONCLUSION: EGPA incidence and prevalence have risen in our region. This may reflect both a true increase in disease burden and the impact of coordinated diagnostic strategies. Similar models could enhance disease recognition in other settings.
Unraveling the role of human endogenous retroviruses in rheumatoid arthritis.
Castaño-López S, Lopera TJ, Martínez-Gutierrez M … +2 more , Velilla PA, Castaño D
Autoimmun Rev · 2026 Apr · PMID 41802452 · Publisher ↗
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and painful joint inflammation that can lead to bone erosion and significant disability if not treated promptly. The etiology of this di...
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and painful joint inflammation that can lead to bone erosion and significant disability if not treated promptly. The etiology of this disease is not fully defined. Multiple genetic, epigenetic, environmental, and immunological factors have been associated with the development and perpetuation of this autoimmune and inflammatory phenomenon. Human endogenous retroviruses (HERVs), retroelements that comprise approximately 8% of the human genome, have been proposed as potential contributors to the loss of immune tolerance and may contribute to the development of RA. Exposure to certain environmental risk factors, cellular activation processes, and inflammation promotes HERV gene expression. Compared with healthy individuals, RA patients exhibit increased transcripts of particular HERVs in blood and synovium, mainly of the HERV-K family. In addition, autoantibodies targeting distinct HERV epitopes have been identified in patients with RA. A better understanding of the role of HERVs in RA, including their epigenetic dysregulation and their activation of the immune system, could be a relevant basis for developing new tools for the detection, diagnosis, and follow-up of patients, as well as for identifying alternative therapeutic targets in those individuals who are refractory to conventional treatments. This review examines the general features of HERVs and their potential role in the immune dysregulation of patients with RA.
Exploring the metabolic mysteries: Mechanistic insights into lactylation-mediated regulation of autoimmune diseases.
Kang N, Wang B, Li Y … +1 more , Zhu R
Autoimmun Rev · 2026 Apr · PMID 41802451 · Publisher ↗
Autoimmune diseases are chronic disorders caused by the immune system's aberrant recognition and attack of self-tissues. Accumulating evidence has revealed that these diseases are closely related to metabolic reprogrammi...
Autoimmune diseases are chronic disorders caused by the immune system's aberrant recognition and attack of self-tissues. Accumulating evidence has revealed that these diseases are closely related to metabolic reprogramming and epigenetic regulation. Lactylation, a recently identified post-translational modification driven by lactate, has emerged as a critical link connecting cellular metabolism to immune regulation. In this review, we provide a comprehensive overview of the regulatory mechanisms and functional roles of lactylation in autoimmune pathogenesis. Lactate, by regulating both histone and non-histone lactylation, affects immune responses in both innate immunity (e.g., macrophages and dendritic cells) and adaptive immunity (e.g., T cells and B cells). The article focuses on exploring the specific regulatory mechanisms of lactate metabolism and lactylation in various autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and Sjögren's syndrome (SS). We describe how lactylation drives disease initiation and progression by modulating inflammatory responses, immune cell infiltration, and tissue damage, offering fresh perspectives on the pathophysiology of autoimmunity. Furthermore, lactylation-associated genes and modification levels demonstrate potential as disease biomarkers, suggesting that targeting lactate metabolic pathways or the involved enzymes can provide new therapeutic strategies and targets for autoimmune diseases.
Vagus nerve stimulation in autoimmune diseases: Mechanisms, therapeutic potential, and clinical applications.
Ye J, Lan Y, Li W … +3 more , Lv H, Wen C, Xu Z
Autoimmun Rev · 2026 Apr · PMID 41796720 · Publisher ↗
Autoimmune diseases characterized by dysregulated immune responses against self-antigens. Current pharmacotherapies are limited by like resistance, side effects, and high costs, highlighting the need for novel interventi...
Autoimmune diseases characterized by dysregulated immune responses against self-antigens. Current pharmacotherapies are limited by like resistance, side effects, and high costs, highlighting the need for novel interventions. Vagus nerve stimulation (VNS) offers a promising alternative through three forms, including implantable, transcutaneous cervical, and transcutaneous auricular. Increasing clinical evidence demonstrates VNS benefits patients with autoimmune disorders, such as treatment-refractory rheumatoid arthritis, Crohn's disease, and systemic lupus erythematosus. Preclinical studies support that VNS attenuates inflammation primarily via the cholinergic anti-inflammatory pathway (CAP) through α7 nicotinic acetylcholine receptor (α7nAChR) activation. Emerging insights implicate β-adrenergic signaling, hypothalamic-pituitary-adrenal (HPA) axis modulation, and gut microbiome regulation. This review summarizes current clinical and preclinical evidence, synthesizes current mechanistic understanding, and addresses key gaps in clinical validation. Future research priorities include conducting large-scale randomized controlled trials to extend VNS applications to broader autoimmune diseases and advancing the neurostimulation efficacy of non-invasive vagus nerve stimulation devices.
Ethics in publishing: From plagiarism to artificial intelligence.
Alnaimat F, AlSamhori ARF, Seiil B … +2 more , Qumar A, Zimba O
Autoimmun Rev · 2026 Apr · PMID 41796719 · Publisher ↗
The digitization of research has transformed how evidence is gathered, hypotheses are generated, and manuscripts are written, introducing ethical challenges related to plagiarism, authorship, and artificial intelligence...
The digitization of research has transformed how evidence is gathered, hypotheses are generated, and manuscripts are written, introducing ethical challenges related to plagiarism, authorship, and artificial intelligence (AI) in medical writing. This structured narrative review, informed by a comprehensive database search (PubMed/MEDLINE, EMBASE, Scopus, and Web of Science; January 2005-March 2026), examines contemporary approaches to prevent plagiarism and ensure the ethical use of AI in medical publishing. While a systematic search of PubMed, EMBASE, Scopus, and Web of Science was applied, the objective was conceptual synthesis rather than quantitative meta-analysis. AI can enhance efficiency and quality, its misuse, through unacknowledged use, over-reliance, or biased outputs, poses a threat to scholarly integrity. Safeguarding trust in medical literature requires a proactive framework that combines plagiarism detection, mandatory AI disclosure, ethical training, and strict editorial oversight. Ultimately, technology may support, but cannot replace, the accountability and ethical responsibility of human authors.
Enthesitis in Spondyloarthritis. From pathogenesis to clinical presentation and imaging: Similarities and differences between PsA and axSpA.
Xynogalas I, Karamanakos A, Galani A … +4 more , Kougkas N, Vassilakis KD, Baraliakos X, Fragoulis GE
Autoimmun Rev · 2026 Apr · PMID 41791558 · Publisher ↗
Radiographic axial spondyloarthritis (r-axSpA), non-radiographic axial spondyloarthritis (nr-axSpA), and psoriatic arthritis (PsA) represent distinct yet overlapping entities within the spondyloarthritis (SpA) spectrum....
Radiographic axial spondyloarthritis (r-axSpA), non-radiographic axial spondyloarthritis (nr-axSpA), and psoriatic arthritis (PsA) represent distinct yet overlapping entities within the spondyloarthritis (SpA) spectrum. Enthesitis has emerged as a unifying hallmark of these diseases, linking mechanical stress, immune dysregulation, and structural remodeling. Understanding similarities and differences in entheseal pathology among these entities may elucidate shared and divergent mechanisms driving disease pathogenesis and progression. Mechanical stress at entheses activates mechanosensitive pathways leading to inflammatory changes and eventually new bone formation. In both research and clinical practice, enthesitis is assessed though the use of clinical indices and imaging modalities, particularly ultrasound and Magnetic Resonance Imaging (MRI), while modern modalities emerge on. Despite shared inflammatory mechanisms, variations in cytokine profiles, soft tissue and underlying bone involvement drive disease-specific patterns of damage and repair in axial and peripheral sites. Combining standardized multimodal imaging with molecular biomarkers holds promise for refining classification, improving early diagnosis, and guiding targeted therapeutic strategies across the SpA spectrum. In this review we explore enthesitis from various standpoints, including pathophysiology, clinical and imaging approaches under the prism of the similarities and differences between PsA and AxSpA.
Mechanisms of environmental risk factors for autoimmune diseases.
Maruvada S, Miller FW
Autoimmun Rev · 2026 Apr · PMID 41780625 · Full text
Over the past few decades, autoimmune diseases have seen a steady upsurge in global prevalence and associated costs. While the exact reasons for these increases are unknown, this trend has been attributed to increased ex...
Over the past few decades, autoimmune diseases have seen a steady upsurge in global prevalence and associated costs. While the exact reasons for these increases are unknown, this trend has been attributed to increased exposure to environmental agents that are also risk factors for autoimmune disease, including xenobiotic chemicals, infections, lifestyle changes, stressful life events, and altered microbiomes, with subsequent biochemical modifications that influence immune tolerance. This review explores current understanding of mechanisms relating to environmental agents contributing to autoimmune diseases. Here we focus on the key initial mechanistic pathways that include environmentally-induced DNA damage, epigenetic alterations, protein post-translational modifications - such as hapten formation, altered autoantigen structure and cellular locations - tissue barrier disruptions, molecular mimicry, and neuroendocrine dysregulation. The processes by which these initial effects result in secondary changes to influence immunological mechanisms, which can then contribute to the development of autoimmunity and autoimmune disorders, are also discussed. While understanding of the mechanisms of environmental triggers in autoimmune diseases has expanded in recent years, and they are considered fundamental architects of autoimmune phenotypes that imprint specific molecular signatures with prognostic and therapeutic value, many important issues remain unaddressed. These include conducting longitudinal exposome studies, defining the necessary and sufficient gene-environment interactions, understanding the synergistic effects of exposure mixtures, of exposure timing and susceptibility, and impacts of chronic psychosocial stress on immune function. Addressing these knowledge gaps and advancing our understanding of the underlying causal pathways are vital for developing preventive strategies and creating safer and more effective therapies for autoimmune conditions.
Mitochondrial transfer and transplantation in the immune cells: Mechanistic foundations, medical applications, and future prospects.
Liu X, Feng X, Zhan D … +1 more , Yin H
Autoimmun Rev · 2026 Mar · PMID 41765357 · Publisher ↗
Mitochondria exhibit tissue-specific physiological functions and are central to the maintenance of cellular homeostasis. Emerging evidence indicates that intercellular mitochondrial transfer is regulated by multiple dete...
Mitochondria exhibit tissue-specific physiological functions and are central to the maintenance of cellular homeostasis. Emerging evidence indicates that intercellular mitochondrial transfer is regulated by multiple determinants and exerts a profound influence on the function of both innate and adaptive immune cells. The underlying mechanisms are highly heterogeneous, involving distinct cellular contexts, microenvironmental cues, and modes of intercellular communication. This review summarizes the major triggers and mechanistic pathways governing mitochondrial transfer in immune cells and immune-related diseases, and discusses the therapeutic potential of this process while highlighting key challenges that currently limit its clinical translation. By integrating recent mechanistic insights and translational perspectives, this review aims to provide a conceptual framework for the development of mitochondrial transfer-based strategies in the treatment of immune-mediated disorders.
Obstetric antiphospholipid syndrome: Advances in pathogenesis.
Wang S, Liu H, Huang W … +3 more , Zeng X, Qin L, Gao R
Autoimmun Rev · 2026 Mar · PMID 41763377 · Publisher ↗
The publication of the 2023 ACR-EULAR classification criteria for antiphospholipid syndrome (APS) has shifted the understanding of APS from a "one-size-fits-all" approach to a more nuanced, subphenotype-based research an...
The publication of the 2023 ACR-EULAR classification criteria for antiphospholipid syndrome (APS) has shifted the understanding of APS from a "one-size-fits-all" approach to a more nuanced, subphenotype-based research and management paradigm. Obstetric APS (OAPS), characterized by obstetric clinical manifestations, represents a distinct subtype with unique underlying pathophysiology. OAPS is now recognized as a multifactorial autoimmune disorder, extending beyond the previously held view that it is solely caused by placental vascular thrombosis or micro-thrombosis. Recent evidence has confirmed that trophoblast dysfunction, inflammation and decidual microenvironmental dysfunction are also critical in the pathogenesis of OAPS. Looking forward, a comprehensive summary of the pathogenesis of OAPS will facilitate progress in both research and clinical management of this condition.
Points to consider for reporting digital ulcers in systemic sclerosis interventional studies: An initiative from the world Scleroderma Foundation digital ulcer ad hoc committee.
Campochiaro C, Maltez N, Suliman Y … +18 more , Alunno A, Alcacer-Pitarch B, Allanore Y, Baron M, Chung L, Del Galdo F, Denton CP, Distler O, Furst D, Galetti I, Giuggioli D, Khanna D, Krieg T, Moinzadeh P, Kuwana M, Matucci-Cerinic M, Pope J, Hughes M
Autoimmun Rev · 2026 Mar · PMID 41740914 · Publisher ↗
BACKGROUND: Digital ulcers (DUs) are among the most painful and functionally disabling complications of systemic sclerosis (SSc), affecting up to 50% of patients. Despite their clinical relevance, interventional studies...
BACKGROUND: Digital ulcers (DUs) are among the most painful and functionally disabling complications of systemic sclerosis (SSc), affecting up to 50% of patients. Despite their clinical relevance, interventional studies on DUs are limited and vary widely in design, definitions, and outcome reporting, hindering comparability and the development of standardized treatment approaches. OBJECTIVES: This initiative, led by an international expert group under the World Scleroderma Foundation (WSF), aims to establish points to consider for the standardized reporting of DUs in interventional studies, improving study quality, interpretability, and clinical relevance. METHODS: A steering committee of SSc experts developed these recommendations based on three systematic literature reviews on local, surgical, and systemic treatments for SSc-DUs. Consensus was achieved through iterative discussion among committee members, without external funding or third-party influence. RESULTS: Seven domains were identified as essential for standardization: (1) a uniform definition and classification of DUs; (2) consistent inclusion and exclusion criteria; (3) standardized primary and secondary outcome measures, including clinical and patient-reported outcomes; (4) detailed reporting of background and concomitant therapies; (5) harmonized local wound care protocols; (6) predefined timing and frequency of assessments; and (7) consideration of seasonal and environmental influences. CONCLUSION: Adopting these standardized reporting principles in future DU trials will enhance the quality and comparability of data, support more robust meta-analyses, and facilitate the development of effective, patient-centered treatment strategies for SSc-related DUs.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe