Autoimmunity最新文献

{"title":"Identification and validation of susceptibility modules and hub genes in polyarticular juvenile idiopathic arthritis using WGCNA and machine learning.","authors":"Junfeng Liu, Jianhui Fan, Hongxiang Duan, Guoming Chen, Weihua Zhang, Pingxi Wang","doi":"10.1080/08916934.2024.2437239","DOIUrl":"10.1080/08916934.2024.2437239","url":null,"abstract":"<p><strong>Background: </strong>Juvenile idiopathic arthritis (JIA), superseding juvenile rheumatoid arthritis (JRA), is a chronic autoimmune disease affecting children and characterized by various types of childhood arthritis. JIA manifests clinically with joint inflammation, swelling, pain, and limited mobility, potentially leading to long-term joint damage if untreated. This study aimed to identify genes associated with the progression and prognosis of JIA polyarticular to enhance clinical diagnosis and treatment.</p><p><strong>Methods: </strong>We analyzed the gene expression omnibus (GEO) dataset GSE1402 to screen for differentially expressed genes (DEGs) in peripheral blood single nucleated cells (PBMCs) of JIA polyarticular patients. Weighted gene co-expression network analysis (WGCNA) was applied to identify key gene modules, and protein-protein interaction networks (PPIs) were constructed to select hub genes. The random forest model was employed for biomarker gene screening. Functional enrichment analysis was conducted using David's online database, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to annotate and identify potential JIA pathways. Hub genes were validated using the receiver operating characteristic (ROC) curve.</p><p><strong>Results: </strong>PHLDA1, EGR3, CXCL2, and PF4V1 were identified as significantly associated with the progression and prognosis of JIA polyarticular phenotype, demonstrating high diagnostic and prognostic assessment value.</p><p><strong>Conclusion: </strong>These genes can be utilized as potential molecular biomarkers, offering valuable insights for the early diagnosis and personalized treatment of JIA polyarticular patients.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2437239"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine modification of THBS1 induced by affluent WTAP promotes Graves' ophthalmopathy progression through glycolysis to affect Th17/Treg balance.","authors":"Lin-Na Li, Jie-Man Wu, Zong-Ji Zheng, Shu-Xian Li, Meng-Yi Cai, Meng-Chen Zou","doi":"10.1080/08916934.2024.2433628","DOIUrl":"10.1080/08916934.2024.2433628","url":null,"abstract":"<p><p>Graves' ophthalmopathy (GO) obvious manifestation is the imbalance of Th17/Treg. N6-methyladenosine (m6A) methylation is an important regulator of Th17/Treg balance. However, few reports narrate how m6A regulators mediate the role of genes in GO progression. We explored the m6A modification of THBS1 mediated by WTAP, and the mechanism by which THBS1 regulated glycolysis and Th17/Treg balance. A total of 12 peripheral blood (4 GO samples, 4 GH samples, and 4 health samples) were collected to measure the percentage of Th17/Treg in monocytes by flow cytometry. RNA sequencing (RNA-seq) combined with MeRIP sequencing (MeRIP-seq) was used to screen differentially expressed and methylated genes. MeRIP-qPCR was performed to evaluate the m6A abundance of THBS1 after WTAP silencing. Glycolysis of CD4⁺ T cells was reflected by the lactate content and glucose uptake. The number of Th17 cells was increased in GO peripheral blood, whereas the Treg cells decreased. RNA-seq acquired 679 differentially expressed genes (308 up-regulated, and 371 down-regulated) in the CD4⁺ T cells of GO compared to healthy control. MeRIP-seq identified 3277 m6A peaks between the GO group and the healthy control group, corresponding with 2744 genes (1143 hypermethylated and 1601 hypomethylated). Combined analysis of RNA-seq and MeRIP-seq showed 81 hypermethylated and up-regulated genes. Among the six candidate genes in the PI3K-signaling pathway, THBS1 was the most significantly differentially expressed and hypermethylated. THBS1 silencing resulted in decreased lactate content and glucose uptake in CD4⁺ T cells. WTAP was significantly upregulated in CD4⁺ T cells of GO, and WTAP silencing significantly reduced m6A abundance and expression of THBS1. Upregulated and hypermethylated THBS1 mediated by WTAP promoted glycolysis of CD4⁺ T cells, affected Th17/Treg balance, and facilitated GO progression. We provided a novel potential target for GO treatment and revealed the molecular mechanism of WTAP and THBS1 in GO under the m6A perspective.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2433628"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical correlations of serum anti-dsDNA immunoglobulin subfamilies in patients with systemic lupus erythematosus (SLE).","authors":"Jing Jing Wang, Ming Wei Lin, Dan Suan, Dimitra Beroukas, Tom P Gordon, Adrian Y S Lee","doi":"10.1080/08916934.2024.2441992","DOIUrl":"10.1080/08916934.2024.2441992","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an extremely heterogenous autoimmune disorder. A key biomarker, the double stranded (ds) DNA autoantibody, provides diagnostic specificity for SLE. We analyzed anti-dsDNA by mass spectrometry (MS) to determine if ascertaining the autoantibody's heavy chain variable region (IGHV) may hold any clinical relevance. A cross-sectional study of 32 SLE patients (75% female) in a single center was performed. Serum anti-dsDNA was subjected to MS analyses. Obtained IGHV subfamilies were correlated with active clinical features of SLE, as determined by medical record reviews. We established significant associations with the presence of IGHV3-15 and active neuropsychiatric lupus (relative risk [RR] 5.71); IGHV3-21, IGHV3-23 and IGHV4-34 and leukopenia (RR 13.70, 2.14 and 10.29 respectively); and IGHV3-23 and serositis (RR 2.41) and cutaneous lesions (RR 2.82). This study provides the first evidence for the clinical benefits of deep anti-dsDNA profiling through MS, and provides an avenue for improving predictive medicine for SLE patients. Future studies with a greater number of patients, and to determine if these subfamilies have direct pathogenic properties are required.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2441992"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of celiac disease, type 1 diabetes, and thyroid disease autoimmunity during the SARS-CoV-2 pandemic in South of Sweden: insights from the TRIAD study.","authors":"Alexander Lind, Maria Naredi Scherman, Samia Hamdan, Daniel Agardh","doi":"10.1080/08916934.2025.2490491","DOIUrl":"10.1080/08916934.2025.2490491","url":null,"abstract":"<p><p>Recent studies have implied an increased incidence of autoimmune diseases following the SARS-CoV-2 pandemic. The objective was to determine if SARS-CoV-2 infections were associated with celiac disease (CD), type 1 diabetes (T1D), and autoimmune thyroid disease (AITD) autoantibodies in a population-based screening when the pandemic hit the South of Sweden during 2021 and 2022. Between August 2021 and June 2022 self-obtained capillary plasma samples were collected from 1088 children at 6-9 years of age and 1185 adolescents at 13-16 years of age, who were randomly invited from the general population to a screening for CD, T1D, AITD, and SARS-CoV-2 antibodies. Among children and adolescents screened for autoantibodies associated with CD, T1D and AITD, the SARS-CoV-2 infection rate was increased in tissue transglutaminase autoantibody (tTGA) positive (13/17; 76.5%) compared with tTGA negative (492/1168; 42.1%) 13-16-year-old individuals (<i>p</i> = 0.0057). There was no association between SARS-CoV-2 infection rate and AITD- or T1D autoantibodies. Our findings indicate a potential association between prior SARS-CoV-2 infection and screening-detected CD autoimmunity in adolescents aged 13-16 years. Further research is needed to elucidate whether ongoing CD autoimmunity increases susceptibility to infection or if SARS-CoV-2 may act as a trigger for CD autoimmunity in genetically and environmentally predisposed individuals.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2490491"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YTHDF1 activates FBW7 transcription by regulating m⁶A-dependent FOXO1 to facilitate inflammatory response in ulcerative colitis-like model.","authors":"Hui Zhang, Meili Xu","doi":"10.1080/08916934.2025.2491717","DOIUrl":"10.1080/08916934.2025.2491717","url":null,"abstract":"<p><p>The prevalence of inflammatory bowel disease (IBD) has increased recently and lacks curative treatments. The involvement of the N6-methyladenosine (m⁶A) reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in ulcerative colitis (UC)-like model was studied in this study. DSS was employed to induce the UC-like condition both <i>in vitro</i> and <i>in vivo</i>. TNF-α, IL-1β, IL-6, and IL-8 secretion levels were analyzed by ELISA assay. Cell vitality was determined by CCK8 assay. FOXO1 mRNA m⁶A level was examined using methylated RNA binding protein immunoprecipitation (Me-RIP) assay. The interactions between YTHDF1 and FOXO1 were analyzed by RIP assay. ChIP and dual luciferase reporter assays were used to explore the relationship between FOXO1 and FBW7. YTHDF1, FOXO1, and FBW7 were overexpressed in DSS-induced colon epithelial cells. YTHDF1 downregulation alleviated DSS-induced inflammation and NF-κB signal activation in colon epithelial cells. Mechanically, YTHDF1 increased FOXO1 mRNA stability in an m⁶A manner. YTHDF1 overexpression prevented the inhibition of FOXO1 knockdown on DSS-induced inflammation in colon epithelial cells. In addition, FOXO1 transcriptionally activated FBW7. Moreover, FOXO1 upregulation abolished the inhibitory effect of FBW7 knockdown on DSS-induced inflammation in colon epithelial cells. Animal experiments also showed that YTHDF1 deletion alleviated inflammatory response in UC-like mice. YTHDF1 promoted inflammatory response in the UC-like model by transcriptionally activating FBW7 through regulating m⁶A-dependent FOXO1.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2491717"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor interacting protein kinase 1 activation and triggering mesangial cells necroptosis in MRL/lpr mice model of lupus nephritis.","authors":"Lin Peng, Xiaodong Xu, Pengcheng Wang, Fan Yang, Xiaodong Zhu, Shuying Yang, Hongguang Xia, Zhihong Liu, Weisong Qin","doi":"10.1080/08916934.2025.2515825","DOIUrl":"10.1080/08916934.2025.2515825","url":null,"abstract":"<p><p>Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE) affecting the kidneys. Receptor-interacting protein kinase 1 (RIPK1) is involved in necroptosis and inflammatory signaling. Here, we investigate the role of RIPK1 kinase activity in the pathogenesis of LN. Immunofluorescent colocalization of necroptosis with podocyte, endothelial cells, and mesangial cells was detected in the kidney of MRL/lpr mice. <i>In vivo</i> studies used ZJU37 (a RIPK1 inhibitor) to treat MRL/lpr mice to evaluate LN pathological alterations. <i>In vitro</i>, mouse mesangial cells were stimulated with DMSO, serum from MRL/lpr mice, and serum + ZJU37 to detect cell viability, cell death status, expression of necroptosis-related molecular proteins, and significant pathway alterations accompanied by necroptosis. We also conducted functional assay to validate the biological significance of the pathway changed. Firstly, the involvement of RIPK1/RIPK3/MLKL-dependent necroptosis was shown in the mesangial cells of MRL/lpr mice. Secondly, we found that ZJU37 inhibited glomerulonephritis, tubulointerstitial lesions, and vasculitis by reducing the necroptosis of mesangial cells in MRL/lpr mice. Moreover, we discovered that mesangial cells are susceptible to necroptosis when stimulated with serum from MRL/lpr animals and identified the primary altered pathways, including cytokine-cytokine receptor interaction and the PI3K-Akt signaling pathway, which could be abolished by ZJU37. Functional assay showed ZJU37 could significantly increase the migration and cell proliferation ability of mesangial cells. RIPK1 activation triggered mesangial cell necroptosis was identified in the kidneys of MRL/lpr mice and Inhibition of RIPK1 could alleviate LN by reducing the necroptosis of mesangial cells.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2515825"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide analysis of abnormal splicing regulators and alternative splicing involved in immune regulation in systemic lupus erythematosus.","authors":"Bing Xu, Yuan Liu, Guangfeng Chen, Ping Jiang, Yuan Qu, Mengjie Wang, Xiliang Kao","doi":"10.1080/08916934.2024.2448463","DOIUrl":"10.1080/08916934.2024.2448463","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disease with complex clinical manifestations and no current cure. Alternative splicing (AS) plays a key role in SLE by regulating immune-related genes, but its genome-wide regulatory mechanisms remain unclear. To investigate the involvement of abnormal splicing regulators and AS events in the immune regulation of SLE. Transcriptome data from the SLE dataset GSE162828 were analyzed for differential gene expression and AS events using bioinformatics tools. Immune infiltration analysis was conducted with CIBERSORT, and co-expression of key splicing factors (SFs) and AS events was assessed using SUVA software. A total of 5144 differentially expressed genes and 73 SFs were identified. Significant immune cell differences were observed between SLE and controls, highlighting SFs such as HNRNPDL, RBM47, TIA1, SSB, and DHX15. Eighty-three AS events were identified, with IRF9 and PTPRC emerging as key regulatory events linked to SLE. Dysregulated SFs influence AS in immune-related genes, affecting immune cell composition and SLE progression. These findings offer potential new therapeutic targets for modulating the immune microenvironment in SLE.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2448463"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CPN2 alleviates cryptorchidism by inhibiting the NF-κB pathway and regulating immune responses.","authors":"Lei Wang, Lu Lu, Xia Guo, Feng Shao, Hai-Jun Ma, Yun Zhou","doi":"10.1080/08916934.2025.2538860","DOIUrl":"10.1080/08916934.2025.2538860","url":null,"abstract":"<p><p>Cryptorchidism, a common male reproductive disorder characterized by undescended testes, is associated with infertility and increased cancer risk. While its etiology remains incompletely understood, accumulating evidence suggests that immune-inflammatory responses contribute to disease progression. This study investigated the role of carboxypeptidase N subunit 2 (CPN2) in modulating immune activation and testicular pathology via the NF-κB signaling pathway. Key regulatory genes were identified through transcriptomic analysis, weighted gene co-expression network analysis (WGCNA), and machine learning approaches. A di-n-butyl phthalate (DBP)-induced rat model of cryptorchidism and CRISPR/Cas9-mediated CPN2 knockout rats were employed, alongside histological, immunohistochemical, Western blotting, and co-culture assays to explore immune activation and spermatogonial cell fate. CPN2 was identified as a pivotal factor that suppresses NF-κB activation and plasma cell infiltration. Its overexpression alleviated inflammatory cytokine production, preserved spermatogonial stem cell proliferation, and reduced apoptosis in both in vivo and in vitro models. These effects were reversed upon NF-κB activation, confirming the regulatory role of the CPN2/NF-κB axis. Our findings reveal that CPN2 mitigates cryptorchidism progression by modulating immune-inflammatory responses, highlighting it as a promising molecular target for non-surgical intervention in this condition.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2538860"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal models of autoimmunity: a relentless pursuit of accurate pre-clinical models.","authors":"Laurence Morel","doi":"10.1080/08916934.2025.2461072","DOIUrl":"10.1080/08916934.2025.2461072","url":null,"abstract":"","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2461072"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration of telomere length and mtDNA copy number in interstitial lung disease associated with rheumatoid arthritis.","authors":"Giada De Benedittis, Andrea Latini, Chiara Morgante, Chiara Bonini, Eneida Cela, Barbara Kroegler, Alessandra Luciano, Marcello Chiocchi, Francesco Cavalli, Josuel Ora, Paola Rogliani, Giuseppe Novelli, Cinzia Ciccacci, Maria Sole Chimenti, Paola Conigliaro, Paola Borgiani","doi":"10.1080/08916934.2025.2473741","DOIUrl":"10.1080/08916934.2025.2473741","url":null,"abstract":"<p><p>Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). The inflammatory response in lung disease is characterized by severe oxidative stress, which enhances cellular senescence. Telomeric shortening and mitochondria dysregulation represent two hallmarks of cellular senescence. The maintenance of telomere length (TL) and mitochondrial DNA (mtDNA) copy number is preserved by many proteins, such as TERF1 and TFAM, respectively. Our aim was to evaluate the TL, the mtDNA copy number and the expression of two regulator gene factors in RA patients with (RA-ILD) and without lung involvement (RA-NILD). Eighty-five RA patients and 21 healthy subjects were enrolled. Relative TL, mtDNA copy number, and expression analysis of <i>TERF1</i> and <i>TFAM</i> genes were measured using qPCR assay. All RA patients present a statistically significant telomere shortening; in particular, RA-ILD patients show shorter TL compared to both controls and RA-NILD. Patients with Usual Interstitial Pneumonia pattern show a more evident shortening of TL. Lastly, both RA-ILD and RA-NILD patients present a significant decrease in mtDNA copy number compared to controls. The analysis of regulatory genes showed an increase in <i>TERF1</i> expression in RA patients compared to controls, also after stratification in the two subgroups, and a decrease in <i>TFAM</i> expression in RA patients compared to controls. These results show that the alteration of TL and mtDNA copy number in RA patients is more evident in the presence of ILD. The hypothesis is that, in these patients, oxidative stress could accelerate the shortening of telomeres and the decrease of mtDNA copy number.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"58 1","pages":"2473741"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}