Journal of autoimmunity最新文献

{"title":"Interferon signatures fuel B cell hyperactivity and plasmablast expansion in systemic lupus erythematosus","authors":"Hugo J. van Dooren ,&nbsp;Yemil Atisha-Fregoso ,&nbsp;Annemarie L. Dorjée ,&nbsp;Tom W.J. Huizinga ,&nbsp;Meggan Mackay ,&nbsp;Cynthia Aranow ,&nbsp;René E.M. Toes ,&nbsp;Betty Diamond ,&nbsp;Jolien Suurmond","doi":"10.1016/j.jaut.2025.103438","DOIUrl":"10.1016/j.jaut.2025.103438","url":null,"abstract":"<div><div>Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an array of autoantibodies, in particular anti-nuclear antibodies (ANA). The disease is also hallmarked by an expansion of plasmablasts (PB) and hypergammaglobulinemia. The mechanisms underlying this hyperactivity and its relation to autoantibody production is not clear. We aimed to characterize B cell hyperactivity in SLE to identify its underlying mechanisms.</div><div>Using deep phenotyping with spectral flow cytometry and scRNAseq, we demonstrate that a high frequency of PB relative to memory B cells marks a subgroup of SLE patients, particularly those with higher disease activity and positive for Sm/RNP autoantibodies. We identified the origin of this phenotype in a prominent IFN signature in PB and increased activation in the switched CD27⁺ memory B cell compartment. PB from this group of SLE patients displayed high levels of CD45RB and somatic hypermutation frequencies similar to memory B cells. Repertoire analysis revealed a highly polyclonal expansion of PB and skewing towards IgG1. B cell hyperactivity correlated with hypergammaglobulinemia, especially increased IgG serum levels.</div><div>In summary, we show for the first time a direct relationship between IFN and PB expansion in a subgroup of SLE patients. Increased activation and differentiation of class-switched B cells driven by IFN may directly underlie PB expansion and hypergammaglobulinemia. These results provide insight into the pathways leading to B cell hyperactivity and autoantibody production which may guide the tailoring of B cell- and IFN-targeted therapies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103438"},"PeriodicalIF":7.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134596","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":"Association between occupational and environmental dust exposure and autoimmune diseases: A systematic review and meta-analysis","authors":"Seunghyun Lee ,&nbsp;Ah-Reum Jo ,&nbsp;Youjin Kim ,&nbsp;Wanhyung Lee ,&nbsp;Xiaoxue Ma","doi":"10.1016/j.jaut.2025.103440","DOIUrl":"10.1016/j.jaut.2025.103440","url":null,"abstract":"<div><h3>Background</h3><div>Occupational and environmental dust exposure is often overlooked, presenting significant public health concerns. Recent studies suggest it may increase the risk of autoimmune diseases. However, previous research has primarily focused on specific diseases or dust types, leaving the broader relationship unclear. A comprehensive meta-analysis are needed to clarify this connection.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed and Google Scholar up to October 2023, following PRISMA guidelines. Study quality was assessed using standard tools, and a random-effects model was used to estimate pooled odds ratio (OR) and 95 % confidence interval (CI), with subgroup analyses by dust type and disease category.</div></div><div><h3>Results</h3><div>From 90 initial records, 19 studies were included. Dust exposure was significantly associated with increased autoimmune disease risk (OR 1.36, 95 % CI 1.13–1.59). Both occupational (OR 1.18, 95 % CI 1.11–1.26) and environmental dust exposure (OR 1.12, 95 % CI 1.04–1.20) were linked to higher risk. Subgroup analysis showed a strong association between silica exposure and connective tissue diseases, particularly granulomatosis with polyangiitis (OR 5.75, 95 % CI 2.79–8.71). Sensitivity analysis confirmed the findings, though publication bias was noted.</div></div><div><h3>Conclusion</h3><div>Our findings highlight a significant association between dust exposure and autoimmune disease risk, underscoring the need for stricter occupational safety measures and environmental regulations. Targeted interventions, such as improved ventilation systems and personal protective equipment (PPE), should be prioritized. Future research should focus on elucidating underlying mechanisms to inform prevention and treatment strategies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103440"},"PeriodicalIF":7.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131073","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":"Passive maternal immunity in children born to women with systemic autoimmune rheumatic disease – A case-control study","authors":"Antonia Mazzucato-Puchner ,&nbsp;Helene Ramspeck ,&nbsp;Valentin Ritschl ,&nbsp;Tanja Stamm ,&nbsp;Valerie Kuczwara ,&nbsp;Alexandra Szlatinay ,&nbsp;Peter Mandl ,&nbsp;Stephan Blüml ,&nbsp;Helmuth Haslacher ,&nbsp;Ulrike Baranyi ,&nbsp;Veronica Falcone ,&nbsp;Daniel Aletaha ,&nbsp;Klara Rosta","doi":"10.1016/j.jaut.2025.103439","DOIUrl":"10.1016/j.jaut.2025.103439","url":null,"abstract":"<div><h3>Introduction</h3><div>The transplacental transfer of maternal antibodies is essential for neonatal immunity but can be affected by maternal health conditions and pregnancy complications. In women with systemic autoimmune rheumatic diseases (SARD) this transfer may be influenced by the autoimmune condition itself and/or the immunosuppressive therapies administered during pregnancy.</div></div><div><h3>Objective</h3><div>This study aimed to assess the transplacental transfer and efficacy of vaccine-induced antibodies in pregnant women with SARD compared to healthy controls.</div></div><div><h3>Methods</h3><div>We enrolled pregnant women with and without SARD pregnancy. Venous blood samples were collected during the third trimester, and umbilical cord blood was obtained postpartum. Antibody titers were assessed using Roche SARS-CoV-2 RBD ECLIA for SARS-CoV-2 and DiaSorin kits for varicella-zoster virus and rubella.</div></div><div><h3>Results</h3><div>25 pregnant women with SARD and 30 healthy controls were analyzed. Of these, 25 women were vaccinated against SARS- CoV-2 during pregnancy. Transplacental antibody transfer was effective in the SARD and in the control groups. Rubella and SARS-CoV-2 antibody levels showed no significant differences in either maternal or cord blood samples. Varicella-zoster virus antibody levels were higher in SARD maternal and cord sera than in controls. In all cases maternal and neonatal antibody titers were highly correlated (p &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Our findings suggest effective maternal-to-fetal antibody transfer in women with SARD both for existing antibodies (varicella-zoster virus, rubella) as well as newly generated ones (anti-Covid Igs generated after vaccination during pregnancy), indicating robust passive immunity in their newborns.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103439"},"PeriodicalIF":7.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of age-associated B cells in systemic lupus erythematosus","authors":"Qin-Yi Su ,&nbsp;Xin-Xin Zheng ,&nbsp;Xin-Ting Han ,&nbsp;Qian Li ,&nbsp;Ya-Ru Gao ,&nbsp;Sheng-Xiao Zhang ,&nbsp;Xiao-Feng Li","doi":"10.1016/j.jaut.2025.103433","DOIUrl":"10.1016/j.jaut.2025.103433","url":null,"abstract":"<div><div>Age-associated B cells (ABCs) are a distinct subset of B cells. This B-cell population expands in the elderly but is also abnormally expanded in patients with autoimmune diseases like systemic lupus erythematosus (SLE). ABC differentiation requires unique signaling stimuli, including BCR stimulation, TLR7 and TLR9 signaling, and the action of cytokines. The role of ABCs in the pathogenesis and treatment strategies of SLE has been a research hotspot in recent years. Possible pathogenic mechanisms include the production of autoantibodies and cytokines, as well as stimulation of spontaneous germinal center. Specifically targeting ABCs is a promising strategy for treating SLE. This article reviews the role of ABCs in SLE. Understanding the origin and differentiation of ABCs and their role in SLE will facilitate the discovery of novel drug targets for the treatment of SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103433"},"PeriodicalIF":7.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912688","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":"Long-term outcomes of idiopathic inflammatory myopathies: a large-scale longitudinal cohort study","authors":"Yiran Chen ,&nbsp;Longyang Zhu ,&nbsp;Chen Zong ,&nbsp;Shiyu Wu ,&nbsp;Xinxin Zhang ,&nbsp;Lingling Huo ,&nbsp;Yongpeng Ge ,&nbsp;Xiaolan Tian ,&nbsp;Fang Chen ,&nbsp;Wei Jiang ,&nbsp;Sizhao Li ,&nbsp;Yu Zuo ,&nbsp;Shanshan Li ,&nbsp;Linrong He ,&nbsp;Chunjia Li ,&nbsp;Hanbo Yang ,&nbsp;Xinyue Xiao ,&nbsp;Lin Liang ,&nbsp;Xia Liu ,&nbsp;Lu Zhang ,&nbsp;Qinglin Peng","doi":"10.1016/j.jaut.2025.103435","DOIUrl":"10.1016/j.jaut.2025.103435","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate mortality, patient-reported outcomes (PROs), and drug-free remission (DFR) in a large well-characterised cohort of idiopathic inflammatory myopathies (IIMs).</div></div><div><h3>Methods</h3><div>This study retrospectively enrolled 1854 patients with IIMs. Follow-up lasted up to 20 years. Mortality was analysed using the standardised mortality ratio (SMR) and Kaplan-Meier survival analysis. PROs and DFR rates were examined in the survivors at the end of follow-up.</div></div><div><h3>Results</h3><div>Of 1854 patients, 348 (18.8 %) died during follow-up, with an overall SMR of 6.82 (95 % confidence interval [CI] 6.11–7.54). Subgroup analysis revealed the highest SMRs in dermatomyositis (DM), followed by antisynthetase syndrome (ASS), and immune-mediated necrotising myopathy, while SMRs in patients with polymyositis indicated no significant mortality difference from general population. Patients with anti-MDA5-positive DM exhibited higher SMRs than those with other IIM serotypes. Respiratory failure was the leading cause of death among patients with IIMs. Patients with DM had the lowest survival rates within the initial nine years of disease duration, whereas patients with ASS exhibited significantly reduced survival after nine years. At the end of follow-up, 17.1 % of patients achieved DFR (cumulative 3-, 5-, and 10-year DFR rates of 6.1 %, 14.9 %, and 29.3 %, respectively). Patients with DM presented with better PROs and higher DFR rates than those with other IIM subtypes.</div></div><div><h3>Conclusions</h3><div>Our data indicated increased mortality in patients with IIM compared with the general population and provided an important foundational understanding of IIMs. These findings emphasise the heterogeneity in the long-term outcomes across IIM subtypes, DM's acute nature, and ASS's progressive course.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103435"},"PeriodicalIF":7.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906442","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":"HLA alleles predisposing to autoimmunity are linked to impaired immunoregulation in patients with juvenile autoimmune liver disease and in their first-degree relatives","authors":"Pengyun Wang ,&nbsp;Muhammed Yuksel ,&nbsp;Stella Gabeta ,&nbsp;Jonathon Graham ,&nbsp;Munther Hussain ,&nbsp;Laura Jayne Blackmore ,&nbsp;Xiaohong Huang ,&nbsp;Dino Hadzic ,&nbsp;Marianne Samyn ,&nbsp;Tassos Grammatikopoulos ,&nbsp;Michael Heneghan ,&nbsp;Rodrigo Liberal ,&nbsp;Maria Serena Longhi ,&nbsp;Giorgina Mieli-Vergani ,&nbsp;Diego Vergani ,&nbsp;Yun Ma","doi":"10.1016/j.jaut.2025.103436","DOIUrl":"10.1016/j.jaut.2025.103436","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Juvenile autoimmune liver disease (JAILD) comprises autoimmune hepatitis and autoimmune sclerosing cholangitis. JAILD-predisposing genes include HLA-DR3,DR7, DR13 and haplotype A1-B8-DR3. Mechanisms leading to liver autoimmunity remain elusive, though JAILD patients have aberrated immunoregulation. We investigated the influence of HLA genes on immune cells, focusing on T-cells and frequency and function of T regulatory cells (Tregs) in JAILD patients, their first-degree-relatives (FDRs) and healthy controls (HCs).</div></div><div><h3>Methods</h3><div>HLA class I and II genotypes were defined by PCR and peripheral blood mononuclear cells were immunophenotyped by FACS in 82 patients, 72 FDRs, 50 HCs. Treg function was tested by inhibition of CD4^posCD25^neg T-cell proliferation. Links between HLA genes, Treg frequency/function, pro-inflammatory/immunoregulatory cytokines, soluble and membrane-bound programmed cell death-1 (PD-1) were investigated.</div></div><div><h3>Results</h3><div>Proportion of subjects carrying HLA DR3/DR7/DR13 was 88 %, 92 %, 64 % in patients, FDRs and HCs. Circulating Treg frequency was lower in patients and FDRs than HCs. Inhibitory capacity of Tregs was lower in patients but similar in FDRs compared to HCs. FDRs possessing HLA DR3/DR7/DR13 genes had Treg frequencies lower than those without. PD-1 ^posCD4^pos T-cells were fewer in patients than HCs; PD-1^posCD8^pos T-cells were fewer in patients and FDRs than HCs. Patient plasma levels of IFN-γ were higher, and ratios of IFN-γ/IL-10 and IFN-γ/IL-2 lower than in HCs. All nine FDRs with autoimmune disorders had HLA DR3/DR7/DR13 genes and lower Treg frequency than those without autoimmune disorders and HCs.</div></div><div><h3>Conclusion</h3><div>We show a link between HLA disease-predisposing genes and defective immunoregulation not only in JAILD patients, but also in their FDRs, who are prone to autoimmune disorders.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103436"},"PeriodicalIF":7.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912689","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":"Microbial dysbiosis fuels STING-driven autoinflammation through cyclic dinucleotides","authors":"Takayuki Shibahara ,&nbsp;Burcu Temizoz ,&nbsp;Shiori Egashira ,&nbsp;Koji Hosomi ,&nbsp;Jonguk Park ,&nbsp;Naz Surucu ,&nbsp;Albin Björk ,&nbsp;Erdal Sag ,&nbsp;Takehiko Doi ,&nbsp;Rabia Miray Kisla Ekinci ,&nbsp;Sibel Balci ,&nbsp;Marjan A. Versnel ,&nbsp;Jun Kunisawa ,&nbsp;Masahiro Yamamoto ,&nbsp;Tomoya Hayashi ,&nbsp;Shuichi Ito ,&nbsp;Yuji Kamiyama ,&nbsp;Kouji Kobiyama ,&nbsp;Peter D. Katsikis ,&nbsp;Cevayir Coban ,&nbsp;Ken J. Ishii","doi":"10.1016/j.jaut.2025.103434","DOIUrl":"10.1016/j.jaut.2025.103434","url":null,"abstract":"<div><div>Aberrant activation of the stimulator of interferon genes (STING) pathway is a hallmark of autoinflammatory disorders such as STING-associated vasculopathy with onset in infancy (SAVI), characterized by systemic inflammation affecting blood vessels, skin, and lungs. Despite its clinical significance, the mechanisms linking STING activation to disease pathology remain poorly defined. In this study, we demonstrated that SAVI mice harboring the N153S STING mutation exhibit diverse disease phenotypes, with a subset developing severe colitis and diarrhea alongside exacerbated systemic inflammation. These diarrheal SAVI mice showed pronounced dysbiosis, marked by reduced short-chain fatty acid-producing bacteria and an enrichment of segmented filamentous bacteria. This microbial imbalance was accompanied by elevated levels of both microbial and host-derived cyclic dinucleotides (CDNs), potent activators of the STING pathway. Notably, antibiotic treatment ameliorated inflammation, underscoring the role of dysbiosis in driving STING-mediated autoinflammation. Furthermore, in SAVI patients, elevated systemic microbial and host-derived CDNs were observed. In conditions such as systemic lupus erythematosus (SLE)—a heterogeneous autoimmune disease with potential STING involvement—systemic microbial CDNs were significantly correlated with disease biomarkers, including type I interferon scores and anti-dsDNA antibodies. In contrast, no such correlations were observed in STING-independent conditions like rheumatoid arthritis (RA). Importantly, this study highlights that both microbial and host-derived CDNs are key drivers of STING activation, suggesting that personalized treatment strategies could target cGAS or the microbiome based on a patient's specific CDN profile. These findings position systemic CDNs as valuable biomarkers and therapeutic targets for STING-driven diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103434"},"PeriodicalIF":7.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906441","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":"Machine learning approach to single cell transcriptomic analysis of Sjogren's disease reveals altered activation states of B and T lymphocytes","authors":"Maxwell McDermott ,&nbsp;Wenyi Li ,&nbsp;Yin-Hu Wang ,&nbsp;Allen Y. Chen ,&nbsp;Rodrigo Lacruz ,&nbsp;Bettina Nadorp ,&nbsp;Stefan Feske","doi":"10.1016/j.jaut.2025.103419","DOIUrl":"10.1016/j.jaut.2025.103419","url":null,"abstract":"<div><div>Sjogren's Disease (SjD) is an autoimmune disorder characterized by salivary and lacrimal gland dysfunction and immune cell infiltration leading to gland inflammation and destruction. Although SjD is a common disease, its pathogenesis is not fully understood. In this study, we conducted a single-cell transcriptome analysis of peripheral blood mononuclear cells (PBMC) from patients with SjD and symptomatic non-SjD controls to identify cell types and functional changes involved in SjD pathogenesis. All PBMCs populations showed marked differences in gene expression between SjD patients and controls, particularly an increase in interferon (IFN) signaling gene signatures. T and B cells of SjD patients displayed a depletion of ribosomal gene expression and pathways linked to protein translation. SjD patients had increased frequencies of naive B cells, which featured a unique gene expression profile (GEP) distinct from controls and had hallmarks of B cell hyperactivation. Non-negative matrix factorization (NMF) also identified several non-overlapping GEPs in CD4⁺ and CD8⁺ T cells with differential usage in SjD patients and controls. Of these, only the Th1 activation GEP was enriched in T cells of SjD patients whereas the other two GEPs were depleted in T cells, emphasizing the important role of Th1 cells in SjD. Our study provides evidence for aberrant and unique gene expression patterns in both B and T lymphocytes of SjD patients that point to their altered activation states and may provide new insights into the pathogenesis of SjD.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103419"},"PeriodicalIF":7.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898606","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":"VEXAS syndrome: A newly identified X-Linked hematoinflammatory disorder – A comprehensive overview of its genetic, molecular, inflammatory, and clinical landscape","authors":"Alpana Singh,&nbsp;Rishabh Chaudhary","doi":"10.1016/j.jaut.2025.103425","DOIUrl":"10.1016/j.jaut.2025.103425","url":null,"abstract":"<div><div>VEXAS (Vacuoles, E1 Enzyme, X-linked, Auto-inflammatory, Somatic) syndrome is a recently identified auto-inflammatory disorder predominantly affecting males over the age of 50. It arises due to somatic mutations in the <em>UBA1</em> gene, an X-linked gene essential for initiating the ubiquitin-proteasome system, leading to dysregulated protein degradation and immune dysfunction. Clinically, VEXAS presents with a diverse array of inflammatory manifestations, including persistent fever, neutrophilic dermatosis, auricular and nasal chondritis, pulmonary infiltrates, ocular inflammation, and venous thrombosis, along with significant haematological abnormalities such as macrocytic anemia, thrombocytopenia, myeloid and erythroid precursor vacuolization, and bone marrow dysplasia. These systemic complications contribute to high morbidity and mortality. Currently, therapeutic strategies remain largely undefined, with treatment focusing on two primary approaches, which are modulating inflammation through corticosteroids, JAK inhibitors, or IL-6 blockade and targeting the mutant hematopoietic clone or allogeneic hematopoietic stem cell transplantation (AHSCT) therapies. Supportive interventions, including red blood cell and platelet transfusions, erythropoiesis-stimulating agents, thromboprophylaxis, and antimicrobial prophylaxis, are crucial in managing disease-associated complications. This review aims to present a comprehensive analysis of VEXAS syndrome, focusing on its genetic underpinnings, pathophysiology, clinical manifestations, diagnostic criteria, and evolving therapeutic strategies. By integrating current findings from the literature and identifying gaps in ongoing research, this review seeks to equip clinicians and researchers with a comprehensive understanding of VEXAS syndrome. Additionally, it aims to guide future investigations toward refining diagnostic strategies, optimizing therapeutic approaches, and ultimately improving patient care and clinical outcomes.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103425"},"PeriodicalIF":7.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886662","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":"PD1+ innate lymphoid cells 3 predict JAK-dependent inflammation in rheumatoid arthritis","authors":"Aditya Arra ,&nbsp;Katrin Vogel ,&nbsp;Irina Han ,&nbsp;Christine Behrendt ,&nbsp;Ildiko Rita Dunay ,&nbsp;Thomas Häupl ,&nbsp;Eugen Feist ,&nbsp;Monika C. Brunner-Weinzierl","doi":"10.1016/j.jaut.2025.103424","DOIUrl":"10.1016/j.jaut.2025.103424","url":null,"abstract":"<div><div>Innate lymphoid cells (ILCs) play a key role in maintaining immune homeostasis and are linked to inflammation and autoimmunity. This study investigates the role of ILCs in the pathogenesis of rheumatoid arthritis (RA) and their response to two targeted therapies - JAK inhibitors (JAKi), which block critical signaling pathways required for their activation, and TNF inhibitors (TNFi), which target a key inflammatory mediator - offering insights into how these interventions shape ILC-driven inflammation.</div><div>ILC distribution correlated with RA activity, as indicated by the DAS28 score, and this imbalance was improved significantly within four weeks of JAKi, underscoring its early therapeutic impact on ILC-mediated inflammation. While levels of ILC3-activating cytokines such as IL-1β and IL-23 declined under JAKi therapy, they remained unchanged with TNFi. Although JAKi and TNFi showed similar treatment efficacy, multivariate regression analysis showed that improvement in DAS28 score was strongly associated with increase in CTLA-4⁺ILC3 and reduction in both PD1⁺ILC3 frequency and systemic IL12p40/IL-23 levels only with JAKi. Notably, this two ILC3 subtypes determined the DAS28 score after 50 d of JAKi. In contrast, patients showing limited response to JAKi (ΔDAS28 &lt; 1.2) maintained high systemic IL-18 levels, a cytokine that induces signaling independent of the JAK pathway, suggesting a potential resistance mechanism. These findings highlight that monitoring PD1⁺ILC3s or IL-12p40/IL-23 may serve as an indicator of JAKi responsiveness, while elevated IL-18 may identify patients benefiting from alternative therapies. These results also emphasize the clinical relevance of targeting innate immunity for more personalized, pathway-focused RA therapies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103424"},"PeriodicalIF":7.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882046","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}