Journal of autoimmunity最新文献

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Post-translationally modified proteins bind and activate complement with implications for cellular uptake and autoantibody formation 翻译后修饰的蛋白质结合并激活补体,影响细胞摄取和自身抗体的形成
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-06-23 DOI: 10.1016/j.jaut.2025.103444
M.D. van den Beukel , L. Zhang , S. van der Meulen , N.V. Borggreven , S. Nugteren , M.C. Brouwer , R.B. Pouw , K.A. Gelderman , A.H. de Ru , G.M.C. Janssen , P.A. van Veelen , R. Knevel , P.W.H.I. Parren , L.A. Trouw
{"title":"Post-translationally modified proteins bind and activate complement with implications for cellular uptake and autoantibody formation","authors":"M.D. van den Beukel ,&nbsp;L. Zhang ,&nbsp;S. van der Meulen ,&nbsp;N.V. Borggreven ,&nbsp;S. Nugteren ,&nbsp;M.C. Brouwer ,&nbsp;R.B. Pouw ,&nbsp;K.A. Gelderman ,&nbsp;A.H. de Ru ,&nbsp;G.M.C. Janssen ,&nbsp;P.A. van Veelen ,&nbsp;R. Knevel ,&nbsp;P.W.H.I. Parren ,&nbsp;L.A. Trouw","doi":"10.1016/j.jaut.2025.103444","DOIUrl":"10.1016/j.jaut.2025.103444","url":null,"abstract":"<div><h3>Introduction</h3><div>Autoimmune diseases, such as rheumatoid arthritis (RA), are characterized by the presence of autoantibodies including those targeting self-proteins modified by post-translational modifications (PTMs). The complement system is known for its role in innate immune defense, but also in clearing debris and induction of antibody responses. We therefore hypothesized that complement could directly bind to PTMs and target PTM-modified proteins for clearance, or stimulate (chronic) inflammation and development of anti-PTM autoimmunity.</div></div><div><h3>Methods</h3><div>Six PTMs were investigated: nitration (Nt), citrullination (Cit), carbamylation (Ca), acetylation (Ac), malondialdehyde-acetaldehyde adducts (MAA) and advanced glycation end-products (AGE). We used mass spectrometry and plate-bound assays to analyze binding of serum proteins to PTM-modified proteins. The impact of complement activation on cellular uptake was studied in phagocytosis assays. The relationship between complement SNPs, and presence of anti-PTM autoantibodies was analyzed in 587 RA patients.</div></div><div><h3>Results</h3><div>Mass spectrometry analysis revealed a strong binding of complement to proteins modified with Ca, Ac, MAA and AGE but not to Nt and Cit. These observations were confirmed by plate-bound assays revealing that Ca-, MAA- and AGE-modified proteins activated the classical pathway, without involving antibodies. Ac activated the lectin pathway through ficolin-3. Complement activation on Ca-, Ac-, MAA- and AGE-coupled beads enhanced phagocytosis. SNPs in complement genes, associated with higher complement activity, were strongly associated with the presence of anti-PTM antibodies in RA patients.</div></div><div><h3>Conclusion</h3><div>Proteins containing the PTMs Ca, Ac, MAA or AGE activate complement. These complement opsonized PTMs increase phagocytosis and may lead to the development of anti-PTM antibodies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"155 ","pages":"Article 103444"},"PeriodicalIF":7.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365099","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}
引用次数: 0
Association between autoimmune diseases and glucagon-like peptide-1 receptor agonists: A real-world evidence study 自身免疫性疾病与胰高血糖素样肽-1受体激动剂之间的关系:一项真实世界的证据研究
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-06-21 DOI: 10.1016/j.jaut.2025.103453
Yun-Jui Lee , Yu-Wei Fang , Mon-Ting Chen , Hung-Hsiang Liou , Tzu-Hao Li , Ming-Hsien Tsai
{"title":"Association between autoimmune diseases and glucagon-like peptide-1 receptor agonists: A real-world evidence study","authors":"Yun-Jui Lee ,&nbsp;Yu-Wei Fang ,&nbsp;Mon-Ting Chen ,&nbsp;Hung-Hsiang Liou ,&nbsp;Tzu-Hao Li ,&nbsp;Ming-Hsien Tsai","doi":"10.1016/j.jaut.2025.103453","DOIUrl":"10.1016/j.jaut.2025.103453","url":null,"abstract":"<div><h3>Introduction</h3><div>The therapeutic advantages of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in diabetes management have been demonstrated. However, their potential association with autoimmune diseases remains unknown. Using a comprehensive real-world dataset, this study compared GLP-1 RAs against dipeptidyl peptidase-4 inhibitors (DPP-4is) with respect to the incidence of autoimmune diseases.</div></div><div><h3>Methods</h3><div>This retrospective cohort study, with an active-comparator and new-user design, analyzed data from the TriNetX US Collaborative Network. We identified 4,841,560 patients aged over 18 years with type 2 diabetes from 1 January 2015 to 31 December 2022. Finally, 412,021 and 383,415 patients were included in the GLP-1 RAs and DPP-4is groups, respectively. Propensity score matching was used to balance baseline characteristics, and hazard ratios (HRs) were estimated with Cox regression models over an eight-year follow-up.</div></div><div><h3>Results</h3><div>After propensity score matching, each group included 290,770 patients. The analysis revealed that patients receiving GLP-1 RAs exhibited significantly higher risks of certain autoimmune conditions, including ulcerative colitis (HR, 1.11; 95 % CI, 1.04–1.19), rheumatoid arthritis (HR, 1.08; 95 % CI, 1.03–1.12), autoimmune thyroiditis (HR, 1.30; 95 % CI, 1.24–1.38), ankylosing spondylitis (HR, 1.30; 95 % CI, 1.13–1.51), and psoriasis (HR, 1.17; 95 % CI, 1.12–1.22), compared to those on DPP-4is. Moreover, sensitivity analyses consistently revealed a significant link between GLP-1 RAs use and autoimmune diseases.</div></div><div><h3>Conclusions</h3><div>This study suggests that compared with DPP-4is, the use of GLP-1 RAs is linked to increased risks of certain autoimmune diseases. Careful monitoring might be required among patients on GLP-1 RAs.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"155 ","pages":"Article 103453"},"PeriodicalIF":7.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335634","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}
引用次数: 0
Autoimmune associated HLAs and T cell autoantigens exhibit common patterns across several autoimmune diseases 自身免疫性相关hla和T细胞自身抗原在几种自身免疫性疾病中表现出共同的模式
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-06-13 DOI: 10.1016/j.jaut.2025.103443
Astrid Brix Saksager , Freja Dahl Hede , Carolina Barra
{"title":"Autoimmune associated HLAs and T cell autoantigens exhibit common patterns across several autoimmune diseases","authors":"Astrid Brix Saksager ,&nbsp;Freja Dahl Hede ,&nbsp;Carolina Barra","doi":"10.1016/j.jaut.2025.103443","DOIUrl":"10.1016/j.jaut.2025.103443","url":null,"abstract":"<div><div>Approximately 80 autoimmune diseases have been identified, with only a few proteins targeted by the immune system in each disease. The rest of the human proteome remains unaffected, indicating that the selection of these specific proteins is not random. Most autoimmune diseases show strong genetic associations with HLA alleles, suggesting a critical role for antigen presentation in autoimmunity.</div><div>In this study, we analyzed validated T cell epitopes and their associated HLAs from 21 autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus, using experimental data from the IEDB. We compared autoantigens to proteins not implicated in autoimmunity, investigated HLA binding motifs, and contrasted autoimmunogenic T cell epitopes with non-autoimmune T cell epitopes.</div><div>Autoantigens, compared to other non-autoimmunogenic proteins, exhibited higher mRNA expression, greater abundance in disease-specific tissues, and were frequently found in exposed subcellular locations such as membranes and extracellular spaces. Disease-associated HLAs showed distinct binding motifs compared to other HLAs, but the autoimmunogenic epitopes themselves did not differ markedly from other T cell epitopes. Autoantigens were enriched on MHC class II presented peptides, and the self-peptides differed from those seen in non-autoimmune contexts.</div><div>Our findings suggest that the interplay between specific HLA class II alleles and specific antigen features play a pivotal role in initiating autoimmune responses, while subsequent T cell activation likely follows typical immune mechanisms.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"155 ","pages":"Article 103443"},"PeriodicalIF":7.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279926","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}
引用次数: 0
Common Toll-like receptor 7 variants define disease risk and phenotypes in juvenile-onset systemic lupus erythematosus 常见的toll样受体7变异定义了青少年发病系统性红斑狼疮的疾病风险和表型
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-06-13 DOI: 10.1016/j.jaut.2025.103451
Yves Renaudineau , Francesca Sposito , Valentina Natoli , Amandine Charras , Jenny Hawkes , Joni Roachdown , Mathieu Fusaro , Eve MD. Smith , Michael W. Beresford , Christian M. Hedrich
{"title":"Common Toll-like receptor 7 variants define disease risk and phenotypes in juvenile-onset systemic lupus erythematosus","authors":"Yves Renaudineau ,&nbsp;Francesca Sposito ,&nbsp;Valentina Natoli ,&nbsp;Amandine Charras ,&nbsp;Jenny Hawkes ,&nbsp;Joni Roachdown ,&nbsp;Mathieu Fusaro ,&nbsp;Eve MD. Smith ,&nbsp;Michael W. Beresford ,&nbsp;Christian M. Hedrich","doi":"10.1016/j.jaut.2025.103451","DOIUrl":"10.1016/j.jaut.2025.103451","url":null,"abstract":"<div><div>Toll-like receptor <em>(TLR)7</em> contributes to type I interferon (IFN) expression in systemic lupus erythematosus (SLE). This study investigated genetic variability of <em>TLR7</em> in 319 juvenile-onset (j)SLE patients from the UK. New generation sequencing was used to associate “common” <em>TLR7</em> variants with demographic and clinical features. Three jSLE-associated variants with <em>in silico</em> predicted impact on gene function presented minor allele frequencies ≥5 %: rs2302267/n.-20T &gt; G (<em>TLR7</em> promoter); rs179008/p.Gln11Leu (missense variant with predicted loss-of-function); and rs3853839/c.∗881C &gt; G (<em>TLR7</em> 3′UTR). The risk to develop jSLE was increased in African/Caribbean girls carrying rs3853839 GC/GG (OR: 1.8; 95 %-CI: 1.2–2.9), while the risk associated with this variant was reduced in European girls (OR: 0.5; 95 %-CI: 0.4–0.7). At inclusion, rs3853839 minor G allele carrier status associated with activity in the mucocutaneous BILAG domain (p = 0.004), “older” age at diagnosis (p = 0.003, Asian), C3 consumption (p = 0.015, boys), and higher anti-dsDNA antibody levels (p = 0.015, African/Caribbean). The negative linkage disequilibrium between rs179008 (T-C/TT) and rs3853839 (CC) associated with increased global disease activity (pBILAG-2004), and activity in the constitutional and musculoskeletal pBILAG domains. Functionally, rs2302267/n.-20T &gt; G, may protect from leukopenia through reduced <em>TLR7</em> promoter activity, while rs3853839/c.∗881C &gt; G-3′UTR increases TLR7 mRNA stability contributing to increased gene expression. In conclusion, common <em>TLR7</em> variants may influence jSLE risk and organ involvement in an ancestry-specific manner. Observations argue for genetic risk stratification and future consideration of gene variants affecting <em>TLR7</em> to guide personalized treatment and care strategies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"155 ","pages":"Article 103451"},"PeriodicalIF":7.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280021","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}
引用次数: 0
The phenotypic and functional characteristics of intrahepatic CD69+CD103+ tissue-resident MAIT cells in primary biliary cholangitis 原发性胆管炎中肝内CD69+CD103+组织驻留MAIT细胞的表型和功能特征
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-06-01 DOI: 10.1016/j.jaut.2025.103442
Qiyun Xia , Zhuwan Lyu , Yudong Zhao , Xiting Pu , Jian Wang , Yuyang Liu , Yujie Zhou , Jun Qian , M.E. Gershwin , Min Lian , Xiong Ma
{"title":"The phenotypic and functional characteristics of intrahepatic CD69+CD103+ tissue-resident MAIT cells in primary biliary cholangitis","authors":"Qiyun Xia ,&nbsp;Zhuwan Lyu ,&nbsp;Yudong Zhao ,&nbsp;Xiting Pu ,&nbsp;Jian Wang ,&nbsp;Yuyang Liu ,&nbsp;Yujie Zhou ,&nbsp;Jun Qian ,&nbsp;M.E. Gershwin ,&nbsp;Min Lian ,&nbsp;Xiong Ma","doi":"10.1016/j.jaut.2025.103442","DOIUrl":"10.1016/j.jaut.2025.103442","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset that plays a significant role in the immunopathology of primary biliary cholangitis (PBC). However, our understanding of the subpopulations involved in hepatic residency have not been elucidated. Herein, our goal was to delineate the phenotypic and functional properties of intrahepatic tissue-resident MAIT cells in PBC.</div></div><div><h3>Methods</h3><div>Liver tissue and intrahepatic mononuclear cells were collected and analyzed by immunohistochemistry, immunofluorescence and flow cytometry. The transcriptome was determined using in vitro generated tissue-resident MAIT cells. FOXM1's immunoregulatory role was evaluated with inhibitor treatment and regulatory features of BHLHE40 were confirmed by CUT&amp;Tag-seq and luciferase assays.</div></div><div><h3>Results</h3><div>In PBC, the frequency of intrahepatic MAIT cell decreased, but tissue-resident (CD69<sup>+</sup>CD103<sup>+</sup>) MAIT cells significantly expanded and expressed a notably pro-inflammatory phenotype, with substantial elevated expression of CXCR3, CXCR6; IL-17A, IFN-γ and T-bet. FOXM1, a transcriptional factor governing cell proliferation cycle, exhibited notably higher expression in tissue-resident MAIT cells than in non-resident MAIT cells. Inhibition of FOXM1 compromised the in vitro expansion of MAIT cells, and impaired the expression of CXCR3, IL-17A, IFN-γ and GM-SCF by tissue-resident MAIT cells. CUT&amp;Tag-seq and luciferase assay revealed a direct regulation of FOXM1 of BHLHE40 expression.</div></div><div><h3>Conclusion</h3><div>Our data reveals a pro-inflammatory role of expanded tissue-resident MAIT cells in PBC mediated via higher expression of effector cytokines, chemokine receptors and a related transcriptional factor. FOXM1 critically regulates MAIT cell proliferation and tissue-resident pro-inflammatory function, via interaction with BHLHE40, and establishes a transcriptional axis linking proliferation to effector responses.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103442"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195607","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}
引用次数: 0
Integrated analysis of polygenic and environmental risk scores for late-onset systemic lupus erythematosus 迟发性系统性红斑狼疮多基因与环境风险评分的综合分析
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-05-28 DOI: 10.1016/j.jaut.2025.103441
Mehmet Hocaoǧlu , Amr H. Sawalha
{"title":"Integrated analysis of polygenic and environmental risk scores for late-onset systemic lupus erythematosus","authors":"Mehmet Hocaoǧlu ,&nbsp;Amr H. Sawalha","doi":"10.1016/j.jaut.2025.103441","DOIUrl":"10.1016/j.jaut.2025.103441","url":null,"abstract":"<div><h3>Objective</h3><div>Polygenic risk scores (PRS) have been constructed to summarize genetic risk but there is limited research on environment-wide analysis of risk factors for systemic lupus erythematosus (SLE). In this study, we performed an environment-wide association study to construct an environmental risk score (ERS) for SLE and compare the risk conferred by ERS and PRS.</div></div><div><h3>Methods</h3><div>A total of 335 incident SLE cases were identified in the UK Biobank and matched 1:10 with age, sex, and ethnic background 3350 healthy controls. We examined the association between 37 environmental factors and SLE, using a univariate followed by a multivariate analysis. We summed the natural logarithm of the odds ratios (OR) of statistically significant environmental variables in the multivariable model to derive an ERS for SLE. Model discrimination was compared by De-Long′s test. PRS was calculated using the ORs of previously reported SLE genetic risk loci.</div></div><div><h3>Results</h3><div>The multivariate analysis revealed the association between daily sunlight exposure, depression, sleeplessness, sex hormone binding globulin levels, and air pollution with increased risk of SLE, while moderate physical activity was a protective factor. Increasing quartiles of the newly developed ERS were associated with similar degree of risk for SLE as the PRS. Integrating PRS with environmental factors significantly improved model performance.</div></div><div><h3>Conclusions</h3><div>We devised an ERS for SLE that summarizes the environmental component of the disease risk. We show that ERS confers a comparable degree of SLE risk as the PRS. Combining genetic and environmental factors could improve risk prediction models in SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103441"},"PeriodicalIF":7.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147273","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}
引用次数: 0
Characterizing local antibody responses in the muscle of inclusion body myositis patients 包涵体肌炎患者肌肉局部抗体反应的表征
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-05-26 DOI: 10.1016/j.jaut.2025.103437
Sahana Jayaraman , Andrew Wilson , Xuwen Alice Zheng , Janelle M. Montagne , Iago Pinal-Fernandez , Andrew L. Mammen , Thomas E. Lloyd , H. Benjamin Larman
{"title":"Characterizing local antibody responses in the muscle of inclusion body myositis patients","authors":"Sahana Jayaraman ,&nbsp;Andrew Wilson ,&nbsp;Xuwen Alice Zheng ,&nbsp;Janelle M. Montagne ,&nbsp;Iago Pinal-Fernandez ,&nbsp;Andrew L. Mammen ,&nbsp;Thomas E. Lloyd ,&nbsp;H. Benjamin Larman","doi":"10.1016/j.jaut.2025.103437","DOIUrl":"10.1016/j.jaut.2025.103437","url":null,"abstract":"<div><h3>Objective</h3><div>Sporadic inclusion body myositis (IBM) is the most common adult idiopathic inflammatory myopathy. IBM etiology has been elusive, due to both degenerative and autoimmune disease features found on muscle biopsy, and significant disease heterogeneity. Investigating the role of antibodies in the muscle of IBM patients may improve our understanding of disease pathogenesis.</div></div><div><h3>Methods</h3><div>We used an IBM xenograft mouse model in which muscle biopsy tissue from IBM patients (n = 98) and controls (n = 131; including 54 from other types of myopathy) were implanted into immunodeficient mice (NOD-Rag1<sup>null</sup>-IL2rγ<sup>null</sup>). We quantified the amount of human IgG, IgA, and IgM in xenografted mouse sera using MesoScale Diagnostics (MSD) assay. We detected donor-derived antibody reactivities targeting autoantigens and infectious agents using Phage ImmunoPrecipitation Sequencing (PhIP-Seq). Finally, we used FR3 AmplifiKation Sequencing (FR3AK-Seq) to sequence the antibody mRNAs from a separate cohort of 146 patient biopsies (14 IBM, 22 healthy controls, 110 other myositis subtypes).</div></div><div><h3>Results</h3><div>With the MSD assay we found human IgG, IgA, and IgM in a larger percentage of IBM xenografted mice versus controls. Using PhIP-Seq, we found anti-microbial reactivities secreted from IBM muscle are prevalent amongst a healthy control population but autoantigen reactivities in IBM are more unique at the peptide and protein level. Additionally, NT5C1A (IgG/IgA and IgM) and TIF1γ (IgG/A) autoantibodies are secreted from muscle tissues of 4/18 and 10/18 IBM xenograft donors, respectively.</div></div><div><h3>Conclusion</h3><div>Our characterization of antibody responses within the muscle of IBM patients reveals that muscle-infiltrating B cells produce both disease-associated autoantibodies and a broad spectrum of antibodies targeting non-self antigens.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103437"},"PeriodicalIF":7.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134595","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}
引用次数: 0
Interferon signatures fuel B cell hyperactivity and plasmablast expansion in systemic lupus erythematosus 干扰素信号促进系统性红斑狼疮患者B细胞过度活跃和浆母细胞扩张
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-05-26 DOI: 10.1016/j.jaut.2025.103438
Hugo J. van Dooren , Yemil Atisha-Fregoso , Annemarie L. Dorjée , Tom W.J. Huizinga , Meggan Mackay , Cynthia Aranow , René E.M. Toes , Betty Diamond , Jolien Suurmond
{"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<sup>+</sup> 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}
引用次数: 0
Association between occupational and environmental dust exposure and autoimmune diseases: A systematic review and meta-analysis 职业和环境粉尘暴露与自身免疫性疾病之间的关系:系统回顾和荟萃分析
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-05-25 DOI: 10.1016/j.jaut.2025.103440
Seunghyun Lee , Ah-Reum Jo , Youjin Kim , Wanhyung Lee , Xiaoxue Ma
{"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}
引用次数: 0
Passive maternal immunity in children born to women with systemic autoimmune rheumatic disease – A case-control study 患有系统性自身免疫性风湿病妇女所生儿童的被动母体免疫-一项病例对照研究
IF 7.9 1区 医学
Journal of autoimmunity Pub Date : 2025-05-22 DOI: 10.1016/j.jaut.2025.103439
Antonia Mazzucato-Puchner , Helene Ramspeck , Valentin Ritschl , Tanja Stamm , Valerie Kuczwara , Alexandra Szlatinay , Peter Mandl , Stephan Blüml , Helmuth Haslacher , Ulrike Baranyi , Veronica Falcone , Daniel Aletaha , Klara Rosta
{"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}
引用次数: 0
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