Journal of autoimmunity最新文献

{"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}

{"title":"The role of gut flora-driven Th cell responses in preclinical rheumatoid arthritis","authors":"Shuanglan Chen ,&nbsp;Lijuan Dan ,&nbsp;Li Xiang ,&nbsp;Qingman He ,&nbsp;Dongsen Hu ,&nbsp;Yongxiang Gao","doi":"10.1016/j.jaut.2025.103426","DOIUrl":"10.1016/j.jaut.2025.103426","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with an immune pathogenesis that evolves over decades. Preclinical RA (PreRA) represents a dynamic immune phase preceding clinical RA, marked by the loss of autoimmune tolerance, the appearance of tissue-invasive effector T cells, and the production of autoantibodies (such as antibodies against citrullinated proteins and rheumatoid factors). Extensive research has demonstrated that gut microbiota influence mucosal T-cell responses, driving the progression of PreRA through multiple mechanisms, including altered intestinal permeability, gene-environment interactions, bacterial antigenic specificity, molecular mimicry, and metabolite production. Environmental risk factors such as smoking, hormonal changes, and high-sodium (Na) diets, may contribute to RA pathogenesis <em>via</em> the gut microbiome. The next challenge in RA research lies in developing therapeutic strategies to intervene during the asymptomatic autoimmune phase, where dietary adjustments, natural compounds, probiotics, and other approaches could effectively modulate gut flora to prevent or delay RA onset.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103426"},"PeriodicalIF":7.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878519","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":"miR-143-3p boosts extracellular vesicles to improve the dermal fibrosis of localized scleroderma","authors":"Jiahui Jin ,&nbsp;Zhe Wang ,&nbsp;Yifan Liu ,&nbsp;Jie Chen ,&nbsp;Miao Jiang ,&nbsp;Lixia Lu ,&nbsp;Jingying Xu ,&nbsp;Furong Gao ,&nbsp;Juan Wang ,&nbsp;Jieping Zhang ,&nbsp;Guo-Tong Xu ,&nbsp;Caixia Jin ,&nbsp;Haibin Tian ,&nbsp;Jingjun Zhao ,&nbsp;Qingjian Ou","doi":"10.1016/j.jaut.2025.103422","DOIUrl":"10.1016/j.jaut.2025.103422","url":null,"abstract":"<div><div>Localized scleroderma (LoSc) is an autoimmune disease that features extensive fibrosis of the skin. Due to its severity and limited understanding, no effective treatments have been developed to date. Bone marrow mesenchymal stem cells (BMSCs) derived extracellular vesicles (EVs) have been demonstrated promising therapeutic effects on the LoSc mouse model in our previous study. However, identifying the targets and underlying mechanisms of EVs remains a significant challenge for therapeutic applications. miR-143-3p, a critical and abundant factor in BMSC-EVs identified through miRNA sequencing, mediates antifibrotic effects in a LoSc mouse model and is significantly lacking in the dermis of LoSc patients. This microRNA inhibits myofibroblast formation and collagen synthesis, contributing to the therapeutic effects of BMSC-EVs in the LoSc mouse model. Moreover, miR-143-3p-reinforced BMSC-EVs demonstrated enhanced therapeutic efficacy compared to normal BMSC-EVs, reducing dermal thickening, collagen deposition, fibroblast differentiation into myofibroblasts, and promoting skin tissue remodeling. IGF1R, highly expressed in the skin of LoSc, was identified as a potential target of miR-143-3p and was inhibited by miR-143-3p-reinforced EVs, thereby modulating the IGF1/IGF1R-AKT/MAPK pathway. In conclusion, miR-143-3p-enriched EVs could be a more efficient candidate for treating dermal fibrosis in LoSc.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103422"},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860272","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":"Systemic immune characteristics predicting toxicity to immune checkpoint inhibitors in patients with advanced breast cancer","authors":"Yalong Qi ,&nbsp;Hewei Ge ,&nbsp;Xiaoying Sun ,&nbsp;Yuhan Wei ,&nbsp;Jingtong Zhai ,&nbsp;Haili Qian ,&nbsp;Hongnan Mo ,&nbsp;Fei Ma","doi":"10.1016/j.jaut.2025.103423","DOIUrl":"10.1016/j.jaut.2025.103423","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for cancer. However, frequent and sometimes life-threatening immune-related adverse events (irAEs) are associated with ICI treatment. Therefore, it is imperative to establish a model for predicting the risk of irAEs to identify high-risk groups, enable more accurate clinical risk‒benefit analysis for ICI treatment and decrease the incidence of irAEs. However, no ideal model for predicting irAEs has been applied in clinical practice. The aim of this study was to analyze the systemic immune characteristics of patients with irAEs and establish a model for predicting the risk of irAEs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a study to monitor irAEs in patients with advanced breast cancer undergoing immunotherapy during and following the treatment course. Peripheral blood mononuclear cells (PBMCs) were collected before and after two cycles of therapy. Mass cytometry time-of-flight (CyTOF) was employed to identify baseline and posttreatment immune cell subpopulations, and the relationships between the proportions of cells in these subpopulations and the occurrence of irAEs were explored. Additionally, we conducted subgroup analyses stratified by the anatomic location and time of onset of irAEs. Furthermore, we developed a logistic regression model to predict the risk of irAEs and validated this model using two independent validation cohorts from the Gene Expression Omnibus (GEO) database (accession numbers GSE189125 and GSE186143).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;By analyzing 106 blood samples and samples from two independent validation cohorts (n = 16 and 60 patients), we found that high proportions of CXCR3&lt;sup&gt;+&lt;/sup&gt;CCR6&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt; T cells and CD38&lt;sup&gt;+&lt;/sup&gt;CD86&lt;sup&gt;+&lt;/sup&gt;CXCR3&lt;sup&gt;+&lt;/sup&gt;CCR6&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells and a low proportion of CXCR3&lt;sup&gt;low&lt;/sup&gt;CD56&lt;sup&gt;dim&lt;/sup&gt; natural killer (NK) cells at baseline were significantly correlated with the incidence of irAEs (&lt;em&gt;P&lt;/em&gt; = 0.0029, &lt;em&gt;P&lt;/em&gt; &lt; 0.001, and &lt;em&gt;P&lt;/em&gt; = 0.0017, respectively). In the subgroup analysis, we observed consistent results in patients with immune-related pneumonitis (ir-pneumonitis) and immune-related thyroiditis (ir-thyroiditis). In the early irAE group, the baseline proportion of CXCR3&lt;sup&gt;+&lt;/sup&gt;CCR6&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt; T cells was greater than that in the late irAE group (&lt;em&gt;P&lt;/em&gt; = 0.011). An analysis of PBMCs before and after ICI treatment revealed thatthe dynamic changes in the proportions of naïve CD4&lt;sup&gt;+&lt;/sup&gt; T cells and CXCR3&lt;sup&gt;low&lt;/sup&gt;CD56&lt;sup&gt;dim&lt;/sup&gt; NK cells were closely related to irAE occurrence. Finally, we ultimately developed a model for predicting the risk of irAEs, which yielded an area under the receiver operating characteristic curve (AUROC) of 0.79 in the training cohort and an AUROC of 0.75 in the single-cell validation cohort (GSE189125).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Concl","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103423"},"PeriodicalIF":7.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860273","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":"Evaluation of minor labial salivary gland focus score in Sjögren's disease using deep learning: a tool for more efficient diagnosis and future tissue biomarker discovery","authors":"Konstantinos N. Panagiotopoulos ,&nbsp;Nikos Tsiknakis ,&nbsp;Dimitrios I. Zaridis ,&nbsp;Clio P. Mavragani ,&nbsp;Athanasios G. Tzioufas ,&nbsp;Dimitrios I. Fotiadis ,&nbsp;Andreas V. Goules","doi":"10.1016/j.jaut.2025.103418","DOIUrl":"10.1016/j.jaut.2025.103418","url":null,"abstract":"<div><h3>Background</h3><div>Sjögren's Disease (SjD) is histopathologically characterized by focal sialadenitis in minor labial salivary gland biopsies (mLSGB), which is evaluated by utilizing the focus score (FS). Focus score ≥1 identification is a critical step of the diagnostic approach and SjD classification. Nonetheless, during mLSGB analysis, FS reporting is neglected in a staggering 17 %, and a degree of inter-observer variability is introduced, even among specialized university centers. As the unmet need for reliable FS reporting is displayed, leveraging artificial intelligence in mLSGB evaluation shows encouraging potential and mandates to be investigated.</div></div><div><h3>Methods</h3><div>Minor LSGBs stained only with hematoxylin and eosin (H&amp;E) during evaluation of individuals with a clinical suspicion of SjD, were randomly chosen from our archive. All mLSGBs were scanned digitally as whole slide images (WSI) and the final dataset was partitioned into a training (70 %) and a test set (30 %). An attention-based deep learning binary classification model was employed for evaluation of mLSGBs positivity (FS ≥ 1 or FS &lt; 1).</div></div><div><h3>Results</h3><div>The final dataset consisted of 271 mLSGBs, with 153 (56 %) having FS &lt; 1 and 118 (44 %) FS ≥ 1. In the FS ≥ 1 subset, 74 (63 %) were in the FS = 1–2 range, and the remaining biopsies had FS &gt; 2, following the expected FS distribution among the typical SjD population. Our model resulted in: AUC = 0.932 (0.881–0.984), sensitivity 87 % (0.733–0.944), specificity 84 % (0.71–0.915) and accuracy 85.2 % (0.763–0.912), achieving better performance from previous works.</div></div><div><h3>Conclusion</h3><div>Artificial intelligence models may overcome the intra-observer biases and inter-observer variability in FS evaluation, reinforcing the diagnosis and biomarker discovery in SjD.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103418"},"PeriodicalIF":7.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855064","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 efficacy and safety of colchicine and anti-IL-1 blockers in FMF: results from the Eurofever multicenter observational study","authors":"Marta Bustaffa ,&nbsp;Saverio La Bella ,&nbsp;Yagmur Bayindir ,&nbsp;Gayane Amaryan ,&nbsp;Romina Gallizzi ,&nbsp;Efimia Papadopoulou-Alataki ,&nbsp;Giovanna Fabio ,&nbsp;Naiera Assalia ,&nbsp;Gil Amarilyo ,&nbsp;Sevcan Bakkaloglu ,&nbsp;Milos Jesenak ,&nbsp;Luciana Breda ,&nbsp;Jordi Anton ,&nbsp;Elizabeth Legger ,&nbsp;Maria Alessio ,&nbsp;Gabriele Simonini ,&nbsp;Donato Rigante ,&nbsp;Laura Obici ,&nbsp;Jasmin Kuemmerle-Deschner ,&nbsp;Ozgur Kasapcopur ,&nbsp;Seza Ozen","doi":"10.1016/j.jaut.2025.103421","DOIUrl":"10.1016/j.jaut.2025.103421","url":null,"abstract":"<div><h3>Introduction</h3><div>The majority of currently available data on familial Mediterranean fever (FMF) come from retrospective national or international studies.</div></div><div><h3>Methods</h3><div>An observational study collected data on the Eurofever international FMF cohort. Patients fulfilling genetic and clinical Eurofever criteria were considered as FMF+. Patients not fulfilling clinical and/or genetic (one VUS or benign variants or negative for <em>MEFV</em> variants) criteria were considered as FMF-. Data on compliance to treatment and quality of life were also recorded.</div></div><div><h3>Results</h3><div>Since November 2024, 876 FMF patients (466 M, 410 F) were enrolled, with a mean follow-up of 2.9 ± 3.1 years. 730 (84 %) patients were classified as FMF+, 146 (16 %) as FMF-, with significant differences in the prevalence of clinical manifestations and treatment response between the two groups. At the last follow-up, 433 patients (50.6 %) still had some disease activity. At the last follow-up 749 (85.5 %) patients received colchicine with a relative under dosage of the drug. Anti-IL-1 treatment was reported in 133 patients (15.2 %), mostly canakinumab (117, 13.4 %). Treatment compliance was generally satisfactory, and adverse events were generally mild.</div></div><div><h3>Conclusions</h3><div>Patients with an FMF-like phenotype who lack genetic confirmation display significant differences in clinical features and duration of attacks and show a less response to treatment during their disease course in respect, and thus, should be considered as FMF-mimics and investigated for other causes. Longitudinal data provides a more detailed comprehension of the long-term burden of FMF and the impact of treatment on disease activity and patients' quality of life.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103421"},"PeriodicalIF":7.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844553","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":"Human regulatory B cells suppress autoimmune disease primarily via interleukin-37","authors":"Luman Wang ,&nbsp;Maria-Ioanna Christodoulou ,&nbsp;Zheng Jin ,&nbsp;Yanmei Ma ,&nbsp;Munnaf Hossen ,&nbsp;Yuan Ji ,&nbsp;Wenjun Wang ,&nbsp;Xueqi Wang ,&nbsp;Eryi Wang ,&nbsp;Rongfei Wei ,&nbsp;Xiaojun Xiao ,&nbsp;Xiaoyu Liu ,&nbsp;Ping-Chang Yang ,&nbsp;Shaojun Xing ,&nbsp;Bingni Chen ,&nbsp;Kaifan Wang ,&nbsp;Jim Yi Huang ,&nbsp;Aysin Tulunay-Virlan ,&nbsp;Iain B. McInnes ,&nbsp;Jing Li ,&nbsp;Damo Xu","doi":"10.1016/j.jaut.2025.103415","DOIUrl":"10.1016/j.jaut.2025.103415","url":null,"abstract":"<div><div>Regulatory B cells (Bregs) are crucial for maintaining homeostasis and controlling inflammation. Although interleukin (IL)-10 has been traditionally suggested as the primary suppressive mechanism of Bregs in both mice and humans, the key functional differences between Bregs in these two species, particularly in the context of disease, is still largely unresolved. IL-37, the latest described immunosuppressive cytokine, is produced in humans but not in mice. Herein we identified the characteristics and functions of IL-37-producing Bregs, that naturally exist in human and can be induced by recombinant IL-37 (rIL-37) and/or Toll-like receptor 9 agonist CpG via different mechanisms. rIL-37 alone is sufficient to prompt IL-37, but not IL-10, production and proliferation of Bregs, whereas CpG elicits IL-37 expression in Bregs independently of IL-10, but dependent on HIF-1α which binds on the enhancer/promoter of the IL-37 gene. Functionally, IL-37⁺ Bregs exhibit superior anti-inflammatory efficacy than IL-37^- Bregs in vitro, as well as in psoriasis and colitis models. However, the frequency of IL-37⁺ Bregs is reduced in patients with psoriasis. Thus, IL-37⁺ Bregs hold significant therapeutic potential for treating various inflammatory disorders, including psoriasis and colitis.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103415"},"PeriodicalIF":7.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838557","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":"Treatment of mixed connective tissue disease: A multicenter retrospective study","authors":"Kevin Chevalier ,&nbsp;Benjamin Thoreau ,&nbsp;Marc Michel ,&nbsp;Bertrand Godeau ,&nbsp;Christian Agard ,&nbsp;Thomas Papo ,&nbsp;Karim Sacre ,&nbsp;Raphaèle Seror ,&nbsp;Xavier Mariette ,&nbsp;Patrice Cacoub ,&nbsp;Ygal Benhamou ,&nbsp;Hervé Levesque ,&nbsp;Cécile Goujard ,&nbsp;Olivier Lambotte ,&nbsp;Bernard Bonnotte ,&nbsp;Maxime Samson ,&nbsp;Félix Ackermann ,&nbsp;Jean Schmidt ,&nbsp;Pierre Duhaut ,&nbsp;Kahn Jean-Emmanuel ,&nbsp;Luc Mouthon","doi":"10.1016/j.jaut.2025.103420","DOIUrl":"10.1016/j.jaut.2025.103420","url":null,"abstract":"<div><h3>Introduction</h3><div>Mixed connective tissue disease (MCTD) is a rare systemic disorder that belongs to connective tissue diseases (CTD). Few studies are available on MCTD treatment.</div></div><div><h3>Methods</h3><div>We conducted an observational study within the French MCTD cohort. Data were collected at diagnosis, during follow-up, and at the last follow-up (LFU). We studied three treatment groups i) no treatment, ii) hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and iii) disease-modifying antirheumatic drugs (DMARDs)/immunosuppressant (IS).</div></div><div><h3>Results</h3><div>Three hundred and fifteen patients were included and followed for 96 [40–156] months. At MCTD diagnosis, 52 (16.5 %) patients were treatment-free, while 224 (71.1 %) received GC and/or HCQ and 39 (12.4 %) received DMARDs and/or IS. During follow-up, 10 (3.2 %) patients remained treatment-free, and 77 (24.4 %) were GC-free. Most patients (n = 271; 85.8 %) received HCQ, and 161 (51.1 %) were treated with DMARDs and/or IS. DMARDs and/or IS, including anti-B cell therapeutics, were more frequently prescribed in patients with musculoskeletal involvement (p &lt; 0.0001), interstitial lung disease (ILD, p &lt; 0.0001) and/or pulmonary arterial hypertension (PAH, p &lt; 0.01). Patients in clinical remission and those who did not evolve to a differentiated CTD (MCTD-dCTD) received significantly less frequently DMARDs and/or IS (including anti-B cell therapeutics; p &lt; 0.0001 for both). Patients who received HCQ at MCTD diagnosis appeared to develop less frequently ILD or PAH (p &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>HCQ and GC were the cornerstones of MCTD treatment and were sufficient to control disease manifestations in nearly half of the patients, reflecting the good prognosis of this disease. DMARDs and IS were used for musculoskeletal involvement, PAH/ILD, and in MCTD-dCTD patients.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103420"},"PeriodicalIF":7.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834430","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}