Journal of Translational Autoimmunity最新文献

{"title":"Biopsy-proven myocarditis: peripheral immunophenotypes correlate with histology, etiology, immunosuppressive therapy","authors":"Cristina Vicenzetto ,&nbsp;Andrea Silvio Giordani ,&nbsp;Anna Baritussio ,&nbsp;Federico Scognamiglio ,&nbsp;Maria Grazia Peloso-Cattini ,&nbsp;Elena Pontara ,&nbsp;Elisa Bison ,&nbsp;Gloria Brigiari ,&nbsp;Giuseppe Tarantini ,&nbsp;Massimo Napodano ,&nbsp;Giuseppe Toscano ,&nbsp;Dario Gregori ,&nbsp;Elisa Carturan ,&nbsp;Monica De Gaspari ,&nbsp;Stefania Rizzo ,&nbsp;Cristina Basso ,&nbsp;Renzo Marcolongo ,&nbsp;Alida Linda Patrizia Caforio","doi":"10.1016/j.jtauto.2026.100355","DOIUrl":"10.1016/j.jtauto.2026.100355","url":null,"abstract":"<div><h3>Background</h3><div>Myocarditis is an inflammatory disease of the myocardium with infectious or immune-mediated/autoimmune etiology; etiology diagnosis relays on endomyocardial biopsy (EMB). High titre serum anti-heart autoantibodies (AHA) define severe autoimmune forms. In autoimmune myocarditis immunosuppression (IS) may be required to prevent progression to dilated cardiomyopathy, heart transplant or death, but it is not always effective. This study aimed to identify non-invasive cellular biomarkers of etiology and response to IS in biopsy-proven myocarditis peripheral blood.</div></div><div><h3>Methods</h3><div>Fifty-eight EMB-proven myocarditis patients out of IS were enrolled and compared with 9 healthy controls and 20 EMB-proven myocarditis on IS. Cells distribution was evaluated by flow cytometry; results were related to clinical, EMB and AHA findings.</div></div><div><h3>Results</h3><div>Compared to healthy controls, plasmacytoid dendritic cells percentage was reduced in autoimmune (p = 0.017), in lymphocytic (p = 0.012) myocarditis patients, in those without extra-cardiac autoimmune diseases (AD, p = 0.01), and in myocarditis not on IS (p = 0.003). Viral myocarditis had higher CD62L+/CD56+ NK cells percentage (p = 0.001) and CCR2 over-expression in intermediate monocytes when compared with autoimmune myocarditis (p = 0.013). Autoimmune myocarditis was characterized by higher Th1/Th2 (p = 0.004) and Th17/Treg ratio (p = 0.008), Th1 (p = 0.028) and Th17 lymphocytes (p = 0.017) percentage vs. healthy controls. A reduction of Treg cells percentage was specific for autoimmune lymphocytic (p = 0.047 vs healthy controls), for AHA-positive myocarditis (p = 0.03 vs healthy controls) and for myocarditis unresponsive to IS (p = 0.036).</div></div><div><h3>Conclusions</h3><div>Biopsy-proven myocarditis patients showed distinct peripheral immunophenotypes of either innate or adaptive immune cells according to different histology, etiology and response to IS, unveiling potential novel non-invasive etiological biomarkers for myocarditis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"12 ","pages":"Article 100355"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic dysregulation of immune-related alternative polyadenylation in systemic lupus erythematosus contributes to patient stratification","authors":"Ziyi Chen ,&nbsp;Jingjing Shi ,&nbsp;Yusuo Meng ,&nbsp;Sidong Xiong ,&nbsp;Hang Ruan","doi":"10.1016/j.jtauto.2026.100378","DOIUrl":"10.1016/j.jtauto.2026.100378","url":null,"abstract":"<div><h3>Background</h3><div>Alternative polyadenylation (APA) is a common post-transcriptional gene regulatory mechanism. Although dysregulated APA is associated with various human diseases, its role in Systemic Lupus Erythematosus (SLE) remains largely unexplored. We systematically characterized immune-related APA alterations in SLE and investigated their potential for clinically useful patient stratification.</div></div><div><h3>Methods</h3><div>We integrated RNA-seq data from multiple SLE cohorts involving peripheral blood samples and quantified APA using the DaPars2. We developed a scoring framework to identify key immune-related APA events (ImmAPA) and their utility for grouping SLE patients. And we used the Connectivity Map to explore potential differences in drug response across ImmAPA groups and examined these associations in an independent SLE cohort treated with an immunosuppressive drug.</div></div><div><h3>Results</h3><div>SLE patients exhibited a recurrent trend in lengthening of the 3′ untranslated region (3′UTR) across cohorts. Twenty key APA regulators showed enhanced associations with these changes in SLE patients. The ImmAPA score can group patients into ImmAPA-high and ImmAPA-low subtypes, reflects activation states, and correlates with disease severity. The ImmAPA score captured complementary transcriptomic variation compared with interferon signature. CMap analysis predicted drugs that could reverse these APA changes, and was supported by follow-up analysis.</div></div><div><h3>Conclusions</h3><div>Our study reveals a recurrent and widespread shift toward 3′UTR lengthening in SLE at peripheral blood transcriptome level. The ImmAPA framework provides a new perspective for SLE patient stratification and offers insights into precision therapeutic strategies in SLE.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"12 ","pages":"Article 100378"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Divergent trajectories of inflammatory bowel disease in East, South, South-East and Central Asia: A comprehensive GBD 2021 analysis’ [J. Transl. Autoimmun. 11 2025 100325]","authors":"Kui Wang,&nbsp;Yunqing Zeng,&nbsp;Shanshan Zhang,&nbsp;Yanqing Li","doi":"10.1016/j.jtauto.2025.100344","DOIUrl":"10.1016/j.jtauto.2025.100344","url":null,"abstract":"","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"12 ","pages":"Article 100344"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix remodeling-associated protein 5 as a novel biomarker for predicting disease activity and endoscopic response to infliximab in Crohn's disease","authors":"Daopo Lin ,&nbsp;Jiayue Xu ,&nbsp;Mengqian Ye ,&nbsp;Luyan Fang ,&nbsp;Tianhao Xia ,&nbsp;Wenyu Tong ,&nbsp;Gokuljayanth Jayaseelan Ranichandra ,&nbsp;Yifan Bao ,&nbsp;Bo Zheng ,&nbsp;Yi Jiang ,&nbsp;Lianpin Wu ,&nbsp;Dingyuan Hu","doi":"10.1016/j.jtauto.2025.100300","DOIUrl":"10.1016/j.jtauto.2025.100300","url":null,"abstract":"<div><div>The primary objective of treating Crohn's disease (CD) is to achieve and sustain endoscopic remission. However, repeated endoscopic examination leads to decreased patient compliance and procedural risks. Non-invasive biomarkers for endoscopic activity of CD are thus promising in clinical use. This study compared proteomic profiles between inflammatory and non-inflammatory intestinal tissues on 10 active CD patients through liquid chromatography–tandem mass spectrometry, and identified 384 differentially expressed proteins. Four candidate secretory proteins (MXRA5, AZU/HBP, CRYAB, DEFA3) were validated via ELISA in serum from 74 CD patients (43 active CD and 31 in remission). Serum MXRA5 levels were notably increased in CD patients in remission compared to active cases (<em>P</em> &lt; 0.001) and showed an inverse correlation with SES-CD scores (r = −0.33, <em>P</em> &lt; 0.05). ROC analysis demonstrated MXRA5's utility in distinguishing endoscopic activity of patients with CD (AUC = 0.80), which was improved when combined with CRP (AUC = 0.89). Besides, higher baseline serum MXRA5 levels predicted better endoscopic response to infliximab (IFX). In conclusion, our study indicates that MXRA5 might serve as a new potential serum biomarker for CD activity and IFX response prediction. Further prospective and muli-center studies are needed to validate its predictive performance.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100300"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of key oxidative phosphorylation-related genes in systemic lupus erythematosus based on transcriptomics and bioinformatics analysis","authors":"Shasha Wang,&nbsp;Hongmin Hu,&nbsp;Jingru Chen,&nbsp;Chengyin Li","doi":"10.1016/j.jtauto.2025.100327","DOIUrl":"10.1016/j.jtauto.2025.100327","url":null,"abstract":"<div><h3>Objective</h3><div>Oxidative phosphorylation (OXPHOS) dysfunction is increasingly recognized as a key factor in systemic lupus erythematosus (SLE) pathogenesis. This study aimed to identify OXPHOS-related core genes as potential SLE biomarkers and therapeutic targets.</div></div><div><h3>Methods</h3><div>mRNA sequencing and GSEA were performed on MRL/lpr mouse kidneys. Cross-species differentially expressed genes (DEGs) were identified by integrating mouse data with human SLE kidney datasets from the Gene Expression Omnibus (GEO). Overlapping DEGs with OXPHOS-related genes from GeneCards, a protein–protein interaction (PPI) network was constructed to screen core genes, followed by GO and KEGG enrichment analyses. Gene expression was validated in SLE whole blood, skin lesions, and immune cell subsets using independent GEO datasets. Diagnostic value was assessed by receiver operating characteristic (ROC) analysis; correlation with disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Drug-target interactions were analyzed via DrugBank and STRING. Key genes were validated by qPCR in MRL/lpr kidneys.</div></div><div><h3>Results</h3><div>The OXPHOS pathway was significantly downregulated in MRL/lpr kidneys. Ten consistently upregulated core genes—CCNA2, KIF11, CDC20, TOP2A, TPX2, AURKB, DLGAP5, FOXM1, MKI67, and CEP55—were identified and enriched in cell cycle regulation and cellular senescence. All ten were upregulated in SLE blood; seven in skin lesions. They were broadly overexpressed in immune cells, especially plasmablasts and CD4⁺ T cells. CDC20, DLGAP5, and CEP55 showed high diagnostic accuracy (AUC &gt;0.8). CCNA2 (r = 0.50) and CDC20 (r = 0.56) correlated significantly with SLEDAI. Six genes interacted with known SLE drug targets. Integrating expression and interaction profiles, CCNA2, AURKB, FOXM1, and MKI67 were prioritized as top therapeutic candidates. Quantitative real-time polymerase chain reaction (qPCR) confirmed CCNA2 and FOXM1 upregulation in MRL/lpr kidneys.</div></div><div><h3>Conclusion</h3><div>This study identifies a systemic OXPHOS-related gene signature in SLE, highlighting promising candidates for diagnosis and targeted therapy.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100327"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A laboratory test to detect gliadin-specific CD4+ T-cells for difficult to diagnose celiac disease","authors":"Daan A.R. Castelijn ,&nbsp;Nicolette J. Wierdsma ,&nbsp;Kim de Buck ,&nbsp;Maaike A. van Bree ,&nbsp;Tracy-Jane T.H.D. Eisden ,&nbsp;Jolien C. Hollander ,&nbsp;Gerd Bouma ,&nbsp;Hetty J. Bontkes","doi":"10.1016/j.jtauto.2025.100301","DOIUrl":"10.1016/j.jtauto.2025.100301","url":null,"abstract":"<div><h3>Objectives</h3><div>Discrepancy between serology and small bowel histology, such as seronegative CD, poses a diagnostic challenge in celiac disease (CD) diagnosis. Recently described methods to detect gliadin-specific T-cells are too laborious even in a specialized diagnostic setting. We developed a method, which can be implemented in specialized diagnostic laboratories.</div></div><div><h3>Methods</h3><div>Gliadin-specific T-cells were analyzed by α1-and α2-gliadin peptide loaded Dextramers (Dm) in healthy controls (HC, n = 18), patients with non-celiac gluten sensitivity (NCGS, n = 9), active CD (aCD, n = 7) and CD on a gluten free diet (GFD, n = 14). Control peptide (CLIP)-loaded Dm were used as background controls. The α-gliadin-Dm:CLIP-Dm ratio was calculated. In CD patients ≥5 years on GFD (n = 8), a randomized two-dose gluten challenge was performed to increase gliadin-specific T-cell frequencies.</div></div><div><h3>Results</h3><div>Gliadin-specific CD4⁺ T-cell frequencies were significantly higher in aCD and GFD than in HC and NCGS (p ≤ 0.0001). In CD patients on a GFD ≥5 years, gliadin-specific T-cells were detectable in 6/8 patients after a week gluten challenge, and all tested positive within 4 weeks. Gliadin-specific T-cells significantly upregulated CD38 after 1 week of gluten ingestion (p &lt; 0.008). Real world data from sixteen patients demonstrated the applicability of this test in diagnostic challenging cases.</div></div><div><h3>Conclusions</h3><div>Gliadin-specific T-cells can be detected in peripheral blood of CD patients using commercially available dextramers. These cells persist in CD patients on a GFD but may decline over time. A short term low-dose gluten challenge increased sensitivity. This simplified detection method of gliadin-specific T-cells is suitable for diagnostic challenging CD cases.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100301"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative mass spectrometry-driven multi-omics and single cell technologies in ankylosing spondylitis: insights into pathogenesis, biomarker discovery, and precision medicine","authors":"Yan Gao ,&nbsp;Xinge Li ,&nbsp;Fengting Luo ,&nbsp;Ruibing Chen ,&nbsp;Xiangyang Zhang","doi":"10.1016/j.jtauto.2025.100319","DOIUrl":"10.1016/j.jtauto.2025.100319","url":null,"abstract":"<div><div>Ankylosing spondylitis (AS), a chronic inflammatory arthritis primarily affecting the axial skeleton, presents significant clinical challenges due to its complex pathogenesis, delayed diagnosis, and heterogeneous therapeutic responses. This review highlights the pivotal role of mass spectrometry (MS)-based multi-omics technologies in elucidating AS pathogenesis, identifying disease-specific biomarkers, and advancing precision medicine for AS. The fundamental principles of MS are outlined, encompassing ionization methods like electrospray and matrix-assisted laser desorption/ionization, mass analyzers such as orbitrap and time-of-flight, and separation systems including liquid and gas chromatography. These technologies enable highly sensitive and comprehensive profiling of proteomes, metabolomes, and lipidomes. Proteomics analyses have revealed dysregulated pathways and identified key biomarkers, including complement components, matrix metalloproteinases and the panel “C-reactive protein + serum amyloid A1”, for distinguishing active AS from healthy controls and stable AS. Metabolomics studies emphasize disturbances in tryptophan-kynurenine metabolism and gut microbiome-derived metabolites, including short-chain fatty acids, thereby linking microbial imbalance to inflammatory responses. A combination of three metabolites (3-amino-2-piperidone, hypoxanthine, and octadecylamine) has shown promise as serum biomarkers for AS diagnosis. Lipidomics profiling reveals significant changes in phospholipid composition. Furthermore, emerging single cell technologies (e.g., mass cytometry) have dissected immune heterogeneity in AS, revealing chemokine signaling dysregulation in monocyte and T-cell subclusters. Persistent challenges and future advancements, such as data heterogeneity, cohort limitations, and the interpretability of artificial intelligence models for multi-omics integration were discussed. By integrating technological innovation with clinical insights, this review systematically summarizes multiple potential biomarker panels for AS, in which multi-omics-driven strategies facilitate early diagnosis, mechanistic subtyping, and personalized therapies, ultimately improving patient outcomes in AS.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100319"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum test for secretory component-containing anti-citrullinated protein antibodies as a novel prognostic tool in rheumatoid arthritis at-risk subjects","authors":"Klara Martinsson ,&nbsp;Simon Åhammar ,&nbsp;Alexandra Cîrciumaru ,&nbsp;Bence Réthi ,&nbsp;Michael Ziegelasch ,&nbsp;Aase Hensvold ,&nbsp;Alf Kastbom","doi":"10.1016/j.jtauto.2025.100317","DOIUrl":"10.1016/j.jtauto.2025.100317","url":null,"abstract":"<div><div>Individuals with autoantibodies against citrullinated proteins (ACPA) and musculoskeletal symptoms face increased risk of developing rheumatoid arthritis (RA). There are knowledge gaps concerning who will develop disease, and predictors of RA onset are highly warranted. A mucosal origin hypothesis in RA is gaining increasing support, for instance by a previous study showing that secretory component-containing ACPA (SC ACPA) in the circulation are prognostic for RA onset. This study aimed to confirm the prognostic value of serum SC ACPA in a large cohort of symptomatic at-risk subjects and to establish a cutoff level for the prognostic use of SC ACPA testing.</div><div>Baseline sera from an observational prospective cohort of IgG ACPA positive individuals with musculoskeletal complaints (Karolinska cohort, n = 266) were tested for SC ACPA by ELISA. SC ACPA levels were increased among subjects subsequently developing arthritis (n = 100, median 62 arbitrary units (AU)/mL) compared to those who did not (n = 166, median 40 AU/mL; p &lt; 0.001). A cutoff level for the optimal discrimination concerning future arthritis onset was established by Youden's index, resulting in 81 subjects (30 %) testing positive for SC ACPA, whereof 45 (56 %) progressed to arthritis. Among those testing negative (n = 185), significantly fewer progressed (n = 55, 30 %; p &lt; 0.001). This cutoff was then tested in the previously studied at-risk cohort (n = 82), revealing similar prognostic performance in both cohorts (sensitivity 45 % and 41 %; specificity 78 % and 81 %). We conclude that serum SC ACPA testing is of potential clinical value in symptomatic at-risk subjects and strengthens the mucosal association in RA development.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100317"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent trajectories of inflammatory bowel disease in East, South, South-East and Central Asia: A comprehensive GBD 2021 analysis","authors":"Kui Wang ,&nbsp;Yunqing Zeng ,&nbsp;Shanshan Zhang ,&nbsp;Yanqing Li","doi":"10.1016/j.jtauto.2025.100325","DOIUrl":"10.1016/j.jtauto.2025.100325","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory bowel disease (IBD) is no longer confined to Western populations; its burden is rising across Asia, a region with marked demographic, economic, and health-system heterogeneity. Quantifying contemporary trends and their drivers is essential for region-tailored policy. We aimed to provide the first continent-wide, methodologically harmonized assessment of temporal trends, demographic–epidemiologic determinants, and projections of IBD burden in Asia.</div></div><div><h3>Methods</h3><div>We extracted country-specific incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for 1990–2021 from the Global Burden of Disease 2021 for 43 Asian countries/territories. Age-standardized rates (ASRs) were summarized using estimated annual percentage change (EAPC). An additive Das-Gupta decomposition apportioned absolute changes in cases and DALYs to population growth, population ageing, and epidemiologic change. Bayesian age–period–cohort models projected burden to 2040.</div></div><div><h3>Results</h3><div>From 1990 to 2021, prevalent IBD cases more than doubled (0.54 million→1.34 million) and incident cases nearly tripled. Age-standardized prevalence (ASPR) and incidence (ASIR) rose by 25 % (EAPC 0.98 %) and 34 % (EAPC 1.17 %), respectively. In contrast, the age-standardized death rate declined from 0.50 to 0.30 per 100 000 (EAPC –1.97 %), and the DALY rate fell by 32 % (16.1 → 11.0 per 100 000; EAPC –1.30 %). Decomposition attributed 56 % of additional prevalent cases to population growth, 20 % to ageing, and 24 % to rising age-specific rates. East Asia showed the fastest proportional rise in ASIR yet the steepest DALY decline; Central Asia maintained the highest per-capita disability load; and Southeast Asia remained a low-burden plateau. Projections indicate continued prevalence growth in South and Central Asia, epidemiologic stabilization in East Asia, and sustained low burden in Southeast Asia by 2040.</div></div><div><h3>Conclusions</h3><div>Asia is experiencing a dual dynamic of expanding IBD caseload alongside improving survival and disability outcomes, with pronounced sub-regional heterogeneity. Demography remains the principal driver of case growth, but genuine increases in age-specific incidence signal ongoing propagation of risk. Strengthening surveillance, expanding equitable access to advanced therapies, and implementing region-specific, longitudinal care pathways are imperative to avert disproportionate future disability and economic loss.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100325"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β1 promotes collagen synthesis in systemic sclerosis via upregulating P4HA3","authors":"Zhaopeng Chen ,&nbsp;Yinru Lin ,&nbsp;Yayi Huang ,&nbsp;Zhixian Chen ,&nbsp;Yao Gong ,&nbsp;Zhiduo Hou ,&nbsp;Ling Lin","doi":"10.1016/j.jtauto.2025.100323","DOIUrl":"10.1016/j.jtauto.2025.100323","url":null,"abstract":"<div><h3>Objective</h3><div>Systemic sclerosis (SSc) is a complex autoimmune disease resulting in fibrosis of skin and internal organs. Despite progress in treatment, SSc carries high mortality due to organ fibrosis. This study aimed to identify a potential antifibrotic therapeutic for the treatment of SSc.</div></div><div><h3>Methods</h3><div>SSc bioinformatics data (GSE181549 and GSE138669) were obtained from the public Gene Expression Omnibus (GEO) database. Subsequently, we conducted differential analysis, Protein–protein interaction (PPI) network construction, gene enrichment analysis to identify a key fibrotic gene, followed by verification.</div></div><div><h3>Results</h3><div>A total of 107 differentially expressed genes were identified through analysis between SSc patients and healthy controls. P4HA3 (α subunit of Collagen prolyl 4-hydroxylases, C-P4Hs) was identified by PPI network analysis. P4HA3 was the sole upregulated gene and positively correlated with the modified Rodnan skin score. PI3K/AKT signaling pathway was enriched by GSEA for single-gene to obtain P4HA3-related pathways. Single-cell analysis detected predominant TGF-β1 upregulation in immune cells, particularly in <em>CD14</em>⁺<em>CD16</em>⁻ monocytes, and P4HA3 showed elevated expression in <em>SFRP2</em>^high fibroblasts. Immunohistochemistry indicated that P4HA3- and TGF-β1-positive cell numbers were elevated in the dermal layers of SSc patients. P4HA3 was also elevated in bleomycin-treated mice and TGF-β1-induced human fibroblasts. Inhibition of C-P4Hs ameliorated experimental fibrosis in bleomycin-treated mice and TGF-β1-induced human fibroblasts. Hydroxyproline levels were reduced following P4HA3 knockdown in human fibroblasts.</div></div><div><h3>Conclusion</h3><div>Our results suggest that P4HA3 is upregulated by TGF-β1 secreted from immune cells to promote collagen synthesis in SSc. Inhibition of C-P4Hs is a potential therapeutic approach for SSc fibrosis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100323"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}