Journal of Translational Autoimmunity最新文献

{"title":"Mendelian randomization study of the causal relationship between autoimmune diseases and anemia using proteomic and genetic data","authors":"Xin Zhuang ,&nbsp;Tianen Pan","doi":"10.1016/j.jtauto.2025.100333","DOIUrl":"10.1016/j.jtauto.2025.100333","url":null,"abstract":"<div><h3>Background</h3><div>Observational studies have suggested a potential association between autoimmune diseases and anemia, but the direction of causality remains unclear. To investigate the potential causal relationship between autoimmune diseases and anemia using Mendelian randomization (MR).</div></div><div><h3>Methods</h3><div>We conducted a bidirectional two-sample MR study using summary-level genetic data from the EBI and FinnGen databases. We examined 21 autoimmune diseases as exposures and anemia as the outcome, and vice versa. Multivariable MR, meta-analysis, and two-step mediation analysis involving 43 candidate mediators were also performed. Proteomic MR and colocalization analyses were used to validate causal relationships involving proteins. Functional annotations including KEGG pathway, GO enrichment, protein–protein interaction networks, and drug enrichment analyses were performed to identify potential therapeutic targets.</div></div><div><h3>Results</h3><div>Genetically determined type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), and primary biliary cholangitis (PBC) were associated with an increased risk of anemia (<em>P</em> &lt; 0.05 in meta-analysis). Reverse MR analyses suggested potential bidirectional causality between anemia and mixed connective tissue disease, hypothyroidism, and asthma. Mediation analysis indicated that hypothyroidism may contribute to anemia by elevating IgG levels. Proteomic and colocalization analyses identified several proteins associated with anemia (e.g., MCCD1, TMEM106B), T1DM (e.g., CTRB1, CTRB2, IL7RA), RA (e.g., TGFBI, IL1RN), and PBC (e.g., ALDH2, CXCL16).</div></div><div><h3>Conclusion</h3><div>This MR study supports a causal effect of certain autoimmune diseases on anemia risk and highlights potential protein targets for intervention, offering new insights for anemia prevention and treatment.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100333"},"PeriodicalIF":3.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518964","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":"Epidemiological assessment of six major immune-mediated inflammatory diseases based on the Global Burden of Disease Study 2021: analyses of age-standardized incidence, prevalence, mortality, and disability-adjusted life years","authors":"Mengyu Huang ,&nbsp;Zhaoli Ma ,&nbsp;Xiu Luo ,&nbsp;Qian Ren","doi":"10.1016/j.jtauto.2025.100330","DOIUrl":"10.1016/j.jtauto.2025.100330","url":null,"abstract":"<div><h3>Objective</h3><div>Immune-mediated inflammatory diseases (IMIDs) are a group of chronic conditions characterized by dysregulated immune responses and tissue inflammation, posing a significant challenge to global health. However, comprehensive epidemiological analysis of the burden of these diseases remains limited. This study aimed to assess the trends in disease burden of six major IMIDs from 1990 to 2021 using the Global Burden of Disease (GBD) 2021 data, providing evidence for targeted prevention and control strategies.</div></div><div><h3>Methods</h3><div>Utilizing GBD 2021 data, we analyzed the epidemiological trends in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized death rate (ASDR), and disability-adjusted life years (DALYs) for six IMIDs across global, 21 regions, 5 Socio-demographic Index (SDI) quintiles, and 204 countries and territories. Joinpoint regression analysis was employed to evaluate temporal trends and calculated the average annual percentage change (AAPC) and its 95% confidence interval (CI).</div></div><div><h3>Results</h3><div>From 1990 to 2021, global ASIR, ASPR, ASDR, and DALYs for asthma, atopic dermatitis (AD), and multiple sclerosis (MS) exhibited declining trends. In contrast, ASIR, ASPR, and DALYs for psoriasis (PsO) showed a comprehensive increasing trend. For inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), ASIR increased significantly, while ASDR and DALYs decreased. Furthermore, significant regional heterogeneity in disease burden was observed: high-SDI regions typically demonstrated higher ASIR and ASPR but lower ASDR; conversely, low-SDI regions exhibited lower ASIR and ASPR alongside higher ASDR.</div></div><div><h3>Conclusion</h3><div>Despite significant spatiotemporal heterogeneity in the burden of the six IMIDs at global and regional levels, they collectively impose a substantial health burden worldwide. Consequently, future efforts require region-specific, differentiated public health interventions to address the ongoing challenge posed by IMIDs to global health systems.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100330"},"PeriodicalIF":3.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568200","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":"Emerging cell-based and cell-free therapeutic strategies for vitiligo","authors":"Nasser Gholijani ,&nbsp;Effat Noori ,&nbsp;Zeinab Zarei-Behjani ,&nbsp;Delsuz Rezaee ,&nbsp;Maryam Khodaei ,&nbsp;Gholamhossien Darya ,&nbsp;Kobra Mehdinejadiani ,&nbsp;Zeinab Dehghan","doi":"10.1016/j.jtauto.2025.100331","DOIUrl":"10.1016/j.jtauto.2025.100331","url":null,"abstract":"<div><div>Vitiligo is a chronic, acquired skin disorder characterized by the loss of pigmentation due to the destruction or dysfunction of melanocytes. Conventional treatments such as corticosteroids and phototherapy often produce limited and unpredictable outcomes. In recent years, novel therapeutic strategies—including both cell-based and cell-free approaches such as melanocyte transplantation, mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), stem cell secretome, and exosomes—have emerged as promising alternatives. These therapies aim to restore pigmentation by replenishing melanocytes, modulating immune responses, and mitigating oxidative stress. This review explores the mechanisms of action, clinical efficacy, and translational challenges associated with each approach. While melanocyte transplantation demonstrates the highest repigmentation success in stable cases, stem cell- and exosome-based therapies offer significant potential for personalized and long-term treatment of vitiligo.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100331"},"PeriodicalIF":3.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519047","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":"Discovery of a PDE4B and PDE4D selective bifunctional degrader for management of chronic inflammatory disorders","authors":"Arvind Shakya ,&nbsp;Qiao Liu ,&nbsp;Chon Lai ,&nbsp;Sherry Baker ,&nbsp;Steven Greene ,&nbsp;Paul Erdman ,&nbsp;Athri Rathnayake ,&nbsp;Angela Schoolmeesters ,&nbsp;Connor M. Blair ,&nbsp;Elka Kyurkchieva ,&nbsp;Navin Rajapakse ,&nbsp;Imelda Lam ,&nbsp;Yuan Yan Sin ,&nbsp;George S. Baillie ,&nbsp;Shenlin Huang ,&nbsp;Aparajita H. Chourasia ,&nbsp;Leah Fung","doi":"10.1016/j.jtauto.2025.100329","DOIUrl":"10.1016/j.jtauto.2025.100329","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by redness and itching, impacting over 15 million individuals in the US. The pathogenesis of AD involves T helper 2 (T_H2) and 17 (T_H17) cytokines, which contribute to increased inflammation, a compromised skin barrier, and heightened susceptibility to infections and allergen sensitization. PDE4, a specific enzyme that degrades cyclic 3′,5′-adenosine monophosphate (cAMP), shows elevated expression in AD patients, maintaining a highly inflammatory environment. Inhibiting PDE4 effectively reduces pro-inflammatory cytokines in several chronic inflammatory diseases. However, current PDE4 inhibitors are often associated with significant adverse effects due to off-target activities. Recent developments in targeted protein degradation techniques have prompted interest in alternative strategies to modulate PDE4 activity with improved selectivity. Consequently, we have developed potent and selective bifunctional degraders for PDE4B/D. These degraders significantly reduce pro-inflammatory cytokine release from activated T cells <em>in vitro</em>, demonstrating a potency which is a thousand times greater than traditional PDE4 inhibitors. In addition, the PDE4B/D degrader (BTX-AP02) efficiently degrades PDE4D in the spleens of treated mice in a dose-dependent manner, with no significant adverse effects at dose levels used in the study. We also demonstrate the efficacy of our lead oral PDE4B/D degrader (BTX-AP04) in a mouse model of graft-versus-host disease (GvHD). Notably, our PDE4D degraders exhibit minimal degradation of known neo-substrates of cereblon (CRBN), indicating high specificity. Taken together, we propose the introduction of a more potent, specific, and safe PDE4B/D degrader as a novel treatment for inflammatory skin conditions such as AD.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100329"},"PeriodicalIF":3.6,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465142","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":"The clinical characteristics and treatment response of myasthenia gravis with positive thyroid peroxidase antibody or thyroid globulin antibody","authors":"Hanyu Xin,&nbsp;Mingou Lu","doi":"10.1016/j.jtauto.2025.100328","DOIUrl":"10.1016/j.jtauto.2025.100328","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Myasthenia gravis (MG) frequently associates with thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), indicating shared autoimmunity. This study investigated the impact of TPOAb/TgAb on MG severity and pathogenesis, to inform improved management.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 144 MG patients (Jan 2022–Dec 2024), stratified into four groups by TPOAb/TgAb status. We compared demographic and clinical profiles, analyzed the effects of disease duration, stage, and onset age on TPOAb/TgAb titers, and evaluated treatment responses across groups.</div></div><div><h3>Results</h3><div>Among 144 included patients, 55.6 % were thyroid antibody (TAb) - positive (TPOAb + TgAb-: 18.8 %; TgAb + TPOAb-: 9.7 %; TPOAb + TgAb+: 27.1 %). Median onset age was 61 years, 67.5 % were female. TPOAb + TgAb- MG primarily presented as MGFA I (70.4 %), initial onset (63.0 %), with low thymoma (3.7 %) and no TitinAb/RyRAb. TPOAb + TgAb + MG exhibited a severe phenotype: higher MGFA III (30.8 %), relapsed (71.8 % vs 50.0 % in TPOAb-TgAb-, P = 0.030), thymoma (43.6 %), and TitinAb/RyRAb positivity (43.6 %/25.6 %). TgAb titers were significantly higher in relapsed MG (P = 0.001). Both TPOAb + TgAb+ and TPOAb-TgAb- MG responded better to pyridostigmine 90 mg/day, TPOAb + TgAb + MG showed superior response to high-dose glucocorticoids (40–60 mg/day) compared to TPOAb-TgAb- (P = 0.006). However, multivariate analysis indicated TPOAb + TgAb + status itself was not an independent predictor (OR = 0.077, 95 % CI: 0.000–23.487; P = 0.380).</div></div><div><h3>Conclusions</h3><div>This study demonstrates the clinical significance of TPOAb/TgAb in MG. TPOAb + TgAb + status identifies a clinical subgroup with a \"triple-high\" profile. TgAb may show potential as a disease activity biomarker. These findings inform precision treatment strategies, pending validation in large prospective studies.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100328"},"PeriodicalIF":3.6,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415241","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":"2025-10-25","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":"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":"2025-10-19","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":"The significance of m6A-circFOXK2 in CD4+T cells from patients with rheumatoid arthritis and circFOXK2 correlates with Th17 % and autophagy","authors":"Qing Luo ,&nbsp;Zhiwei Wu ,&nbsp;Qiuyun Xiao ,&nbsp;Mengfan Lan ,&nbsp;Shiqian Wang ,&nbsp;Peng Fu ,&nbsp;Biqi Fu ,&nbsp;Zikun Huang ,&nbsp;Junming Li","doi":"10.1016/j.jtauto.2025.100326","DOIUrl":"10.1016/j.jtauto.2025.100326","url":null,"abstract":"<div><h3>Objective</h3><div>CD4⁺T cells are significant compositions of immune cells in rheumatoid arthritis (RA) and the aberrant function of CD4⁺T cells have been demonstrated to promote RA's progression. N6-methyladenosine (m6A) is a highly enriched modification found in CircRNAs. However, the role of m6A-methylated circRNA in regulation of CD4⁺T cells function in RA and its association with RA disease activity are presently unclear.</div></div><div><h3>Methods</h3><div>We used m6A-circRNA epitranscriptomic microarray analysis and m6A RNA immunocoprecipitation-quantitative polymerase chain reaction (MeRIP-qPCR) to screen and verify the differentially expressed m6A-methylated circRNAs in CD4⁺T cells from RA and HC.</div></div><div><h3>Results</h3><div>Many m6A-methylated circRNAs were differentially expressed in patients with new-onset RA. M6A-methylated circFOXK2 in the CD4⁺T cells of patients with new-onset RA was significantly decreased, the expression level of circFOXK2 in the CD4⁺T cells of patients with new-onset RA was significantly increased and correlated with treatment, Th17 %, autophagy. CircFOXK2 could function as competing endogenous RNAs to regulate miR-486-3p expression. In many m6A regulators, only a-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) was significantly increased in the CD4⁺T cells of patients with new-onset RA, and its level positively correlated with rheumatoid factor, the expression of circFOXK2. Moreover, the change of ALKBH5 could affect the level of m6A and circFOXK2 in Jurkat cell line.</div></div><div><h3>Conclusion</h3><div>We indicated a notable decrease in the m6A-methylated level of circFOXK2 in CD4⁺T cells from human RA, indicating a potential role of hypomethylated circFOXK2 in CD4⁺T cells function and RA pathogenesis. This may show valuable insight into the ALKBH5/m6A-circFOXK2/miRNA interaction network and the mechanism of RA.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100326"},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319466","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":"Novel variants in ARID1B, SPSB1, and RAET1-AS shape genetic susceptibility and protection in systemic lupus erythematosus and lupus nephritis","authors":"Hung-Yi Chen ,&nbsp;Feng-Cheng Liu ,&nbsp;Hsian-Cheng Chen ,&nbsp;Tan-Mei Liu ,&nbsp;Fu-Chiang Yeh ,&nbsp;Yu-Tien Chang","doi":"10.1016/j.jtauto.2025.100322","DOIUrl":"10.1016/j.jtauto.2025.100322","url":null,"abstract":"<div><h3>Background</h3><div>Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation affecting multiple organs, most notably lupus nephritis (LN). Genetic susceptibility significantly contributes to disease severity and prognosis. However, genomic studies specific to Taiwanese SLE patients, particularly those focusing on LN, remain limited. This study aimed to identify genetic variants associated with SLE and LN in a Taiwanese cohort.</div></div><div><h3>Methods</h3><div>Genome-wide association studies (GWAS) were performed on 276 Taiwanese SLE patients compared with 3393 patients with other rheumatic diseases. Single-nucleotide polymorphism (SNP) genotyping was conducted using the Taiwan Precision Medicine Array, with analyses adjusted for age, sex, and population structure. Functional annotations and biomarkers of renal function were assessed for identified SNPs.</div></div><div><h3>Results</h3><div>Compared with patients with other rheumatic diseases, a novel protective variant, rs9480438 (ARID1B), was identified in the SLE group, suggesting an association with dysregulation of cell cycle checkpoints. In the LN group, a protective variant, rs1294028 (SPSB1), and a risk variant, rs17079029 (RAET1-G/RAET1-AS), were linked to altered serum biomarkers and potential pathogenesis influenced by TGFβ and NK cells.</div></div><div><h3>Conclusions</h3><div>Novel genetic variants related to immune regulation and autoimmunity in Taiwanese SLE and LN patients were identified. These variants provide insight into disease mechanisms and may guide early detection and personalized therapeutic approaches.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100322"},"PeriodicalIF":3.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145320216","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":"2025-10-06","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}