Journal of autoimmunity最新文献

{"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}

{"title":"Preventing the antigen-presenting function of retinal microglia blocks autoimmune neuroinflammation by dendritic cell-primed CD4+ T cells","authors":"Shintaro Shirahama ,&nbsp;Yoko Okunuki ,&nbsp;May Y. Lee ,&nbsp;Margarete M. Karg ,&nbsp;Nasrin Refaian ,&nbsp;Drenushe Krasniqi ,&nbsp;Kip M. Connor ,&nbsp;Meredith S. Gregory-Ksander ,&nbsp;Bruce R. Ksander","doi":"10.1016/j.jaut.2025.103417","DOIUrl":"10.1016/j.jaut.2025.103417","url":null,"abstract":"<div><div>Autoimmune uveitis is a major cause of blindness and experimental autoimmune uveitis (EAU) is mediated by interphotoreceptor retinoid-binding protein specific effector CD4⁺ T cells that infiltrate the retina. At least two MHC Class II (MHC II) antigen-presenting cell (APC) events are required for uveitis to develop. The first occurs in the secondary lymphoid organs when dendritic cells (DCs) activate and expand effector CD4⁺ T cells that enter the circulation and migrate systemically. The second APC event occurs when DC-primed effector CD4⁺ T cells infiltrate the retina and are restimulated by the relevant autoantigen. Importantly, if this second restimulation does not occur, then uveitis does not develop. However, it is still unclear which cell type(s) function as APCs within the retina. There are two candidate MHC II⁺ cell types-resident microglia and infiltrating DCs. We used the inducible Cre-lox approach to develop mouse strains in which MHC II was knocked out specifically on microglia using either the <em>P2ry12</em> or <em>Tmem119</em> gene to drive recombination. We also used <em>Itgax</em> (CD11c encoding gene) to drive recombination in DCs. Using this approach, we uncovered that the second APC event was mediated by MHC II⁺ microglia and not infiltrating MHC II⁺ DCs. Therefore, microglia are an important therapeutic target that can prevent and/or diminish uveitis even in the presence of circulating retinal autoantigen-specific effector CD4⁺ T cells.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103417"},"PeriodicalIF":7.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834429","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":"Clinical targeted treatment in Sjogren's disease: A systematic literature review for an evidence-based medicine approach","authors":"Annalisa Marino ,&nbsp;Irene Genovali ,&nbsp;Luca Navarini ,&nbsp;Elena Pontarini ,&nbsp;Marta Vomero ,&nbsp;Damiano Currado ,&nbsp;Andrea Pilato ,&nbsp;Letizia Pia Di Corcia ,&nbsp;Michele Bombardieri ,&nbsp;Roberto Giacomelli ,&nbsp;Onorina Berardicurti","doi":"10.1016/j.jaut.2025.103416","DOIUrl":"10.1016/j.jaut.2025.103416","url":null,"abstract":"<div><div>Sjögren's disease is a systemic autoimmune disease that primarily affects the exocrine glands, causing the main symptoms of xerostomia and xerophthalmia. In about half of the patients, it also causes systemic symptoms, which can potentially involve any organ or system. To date, the management of these patients is particularly complex due to the lack of recognized and approved therapies for the disease, except for medications used as symptomatic treatment for dryness. Due to the limited evidence available, therapeutic decisions in daily practice are frequently based on a combination of expert opinions and personal experience, which can vary significantly between clinicians. On these bases, we performed as systematic literature review critically analyzing the results of the previous trials, unpacking the single domains of ESSDAI, to evaluate if there are treatments significantly effective in some manifestations of the disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103416"},"PeriodicalIF":7.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792079","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":"Neutrophil extracellular traps induce trophoblasts pyroptosis via enhancing NLRP3 lactylation in SLE pregnancies","authors":"Haoyue Hu ,&nbsp;You Peng ,&nbsp;Chi Chiu Wang ,&nbsp;Jun Chen ,&nbsp;Xiao Yu ,&nbsp;Xiaoyan Chen ,&nbsp;Haotong Ouyang ,&nbsp;Qin Huang ,&nbsp;Jing Ma ,&nbsp;Qian Yin ,&nbsp;Lien Ma ,&nbsp;Ziling Ding ,&nbsp;Minyi Zhang ,&nbsp;Hao Ren ,&nbsp;Jiaman Zheng ,&nbsp;Wenqian Chen ,&nbsp;Zixin Tao ,&nbsp;Ruiyan Liu ,&nbsp;Lu Chen ,&nbsp;Xuefei Wang ,&nbsp;Mei Zhong","doi":"10.1016/j.jaut.2025.103411","DOIUrl":"10.1016/j.jaut.2025.103411","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder primarily affecting women during the reproductive years, often complicating pregnancy outcomes with elevated levels of neutrophil extracellular traps (NETs) infiltration. However, potential impacts of NETs on placental trophoblasts in SLE and the underlying molecular mechanisms remain unclear. To address this, transcriptome sequencing was conducted on placentas collected from seven pregnant women with SLE and six healthy pregnant controls to identify SLE-specific placental features. The effects of NETs were further assessed in MRL/lpr lupus-prone mice and pristane-induced lupus (PIL) mice, focusing on pregnancy outcomes and placental pathology. <em>In vitro,</em> trophoblasts were stimulated with NETs derived from patients with SLE, followed by molecular analyses such as transcriptomic, cellular energy metabolism assays and liquid chromatography-tandem mass spectrometry to explore the effects and mechanisms of NETs. Results showed elevated NETs were observed in the placentas of both patients with SLE and lupus mouse models, accompanied by activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. Treatment with DNase I significantly improved pregnancy outcomes in MRL/lpr mice, while the use of peptidyl arginine deiminase 4 (PAD4)-deficient mice was beneficial on the pregnancy outcomes of PIL mice. Furthermore, SLE-derived NETs activated pyroptosis in trophoblasts by promoting glycolysis and subsequent lactylation of NLRP3. These findings highlight that NETs contribute to placental damage in SLE by inducing the lactylation of the NLRP3 inflammasome in trophoblasts, demonstrating the therapeutic potential of inhibiting NETs to improve placental function.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103411"},"PeriodicalIF":7.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759447","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":"Integrated stress response inhibition restores hsa-miR-145-5p levels after IFN-β stimulation in salivary gland epithelial cells. Association between cellular stress and miRNA biogenesis in Sjögren's disease","authors":"Isabel Castro ,&nbsp;Patricia Carvajal ,&nbsp;Sergio Aguilera ,&nbsp;María-José Barrera ,&nbsp;Soledad Matus ,&nbsp;Sergio González ,&nbsp;Claudio Molina ,&nbsp;María-Julieta González","doi":"10.1016/j.jaut.2025.103412","DOIUrl":"10.1016/j.jaut.2025.103412","url":null,"abstract":"<div><div>Labial salivary glands (LSG) from Sjögren's disease (SjD) patients are characterized by increased levels of pro-inflammatory cytokines, such as type I interferons (IFN-I). These LSG also show activation of the integrated stress response (ISR) with overexpression of protein kinase R (PKR), a known IFN-stimulated gene. <em>In vitro</em>, IFN-I stimulation reproduces the downregulation of hsa-miR-145-5p, which is associated with TLR4 overexpression observed in LSG of SjD patients. MicroRNA levels depend on its biogenesis, which is a multi-step process involving several protein complexes. It is not known whether altered miRNA biogenesis is associated with the activation of the ISR induced by IFN-I in LSG from SjD. The aim of this study was to characterize the expression and localization of components of the miRNA biogenesis machinery in LSG of SjD patients, to assess the effect of pro-inflammatory cytokines on these components, and to test whether inhibition of the IFN-β-induced ISR restores the levels of hsa-miR-145-5p. In LSG from 12 SjD patients and 11 non-SjD sicca controls, we determined mRNA fold changes, relative protein levels, and the localization of the ISR and miRNA biogenesis machinery components by RT-qPCR, Western blot, and immunofluorescence, respectively. Pro-inflammatory cytokines, the ISR inhibitor ISRIB, and the PKR inhibitor C16 were used for <em>in vitro</em> assays. In LSG from SjD patients, PKR and its activator PACT colocalized in the cytoplasm, whereas the PKR inhibitor TRBP was observed in the nuclei. IFN-β activates PKR, increases p-eIF2α and ATF4 levels, and increases PACT and AGO2 detection in stress granules. C16 inhibits PKR phosphorylation but increases ATF4 by activating GCN2. ISRIB restores levels of hsa-miR-145-5p and its target TLR4 mRNA upon IFN-β stimulation. These findings suggest an association between inflammation, cellular stress, and miRNA biogenesis, where modulation of the ISR emerges as a potential strategy to restore cellular homeostasis in LSG from SjD patients.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103412"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748148","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}