Journal of Translational Autoimmunity最新文献

{"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}

{"title":"Immune responses to infection and autoimmune diseases in the UK biobank","authors":"Choa Yun ,&nbsp;Dongwon Yoon ,&nbsp;Sun Young Jung ,&nbsp;Moonsuk Kim ,&nbsp;May A. Beydoun ,&nbsp;Lenore Launer ,&nbsp;Minkyo Song","doi":"10.1016/j.jtauto.2025.100315","DOIUrl":"10.1016/j.jtauto.2025.100315","url":null,"abstract":"<div><h3>Background</h3><div>Infections may trigger autoimmunity, but large-scale studies on antibodies to infections and their associations with autoimmune diseases are limited. We aim to better understand the etiologic role of infection.</div></div><div><h3>Methods</h3><div>We analyzed 9429 UK Biobank participants for 45 antibody responses to 20 pathogens. Association between seropositivity and autoimmune diseases was assessed with logistic regression for prevalence and Cox regression for incidence, applying Bonferroni correction. 49 autoimmune diseases were ascertained via International Classification of Diseases codes and self-reported diagnoses, of which 14 were analyzed.</div></div><div><h3>Results</h3><div>At baseline, 671 (7.1 %, 58 % female) had at least one autoimmune disease. In males, HSV-1 seropositivity was linked to lower odds of rheumatic fever/rheumatic heart disease (odds ratio 0.29 [95 % CI 0.12–0.68]), at Bonferroni significance. At nominal significance (p &lt; 0.05), eight associations were observed—positive: HHV-6B–type 1 diabetes, <em>H. pylori</em>–sarcoidosis, HPV-18–type 1 diabetes, JCV–psoriasis; inverse<strong>:</strong> <em>T. gondii</em>–celiac disease, <em>H. pylori</em>–Crohn’s disease, HSV-1–multiple sclerosis, HHV-7–rheumatoid arthritis. Of 8758 autoimmune disease-free individuals, 627 developed autoimmune diseases. In females, seropositivity to HPV-18 was associated with rheumatoid arthritis (hazard ratio 2.26 [95 % CI 1.34–3.82]), at Bonferroni significance. HRs for 3 nominal seropositivity/autoimmune disease associations (1 inverse, 2 positive) ranged from 0.42 [95 % CI 0.21–0.87] (HHV-6B/vasculitis) to 3.62 [95 % CI 1.29–10.12] (<em>C. trachomatis</em>/psoriasis) in both sexes.</div></div><div><h3>Conclusions</h3><div>This study examined cross-sectional and prospective associations between antibodies to infectious agents and autoimmune diseases. Inverse associations may suggest infections could train the immune system or reflect altered host immunity, while positive associations indicate potential autoimmune triggers. These findings enhance understanding of autoimmune disease etiology and provide a foundation for future mechanistic studies and hypothesis-driven research.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100315"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157597","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":"Clinical efficacy and immunomodulation of double-filtration plasmapheresis in autoimmune encephalitis: A prospective study highlighting the importance of timely initiation","authors":"Hongyan Li ,&nbsp;Kan Wang ,&nbsp;Qiuju Li ,&nbsp;Xuzhong Pei ,&nbsp;Jie Ding ,&nbsp;Jing Peng ,&nbsp;Wanwan Li ,&nbsp;Xiajun Zhou ,&nbsp;Desheng Zhu ,&nbsp;Yangtai Guan","doi":"10.1016/j.jtauto.2025.100318","DOIUrl":"10.1016/j.jtauto.2025.100318","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Double-filtration plasmapheresis (DFPP) has emerged as a plasma-saving alternative to therapeutic plasma exchange for autoimmune encephalitis (AE), but prospective evidence regarding its dual effects on both clinical efficacy and immunomodulation remains limited. This study aimed to evaluate the clinical and immunological effects of DFPP in AE.</div></div><div><h3>Methods</h3><div>In this prospective single-center cohort study, 57 patients diagnosed with AE according to international criteria were enrolled between 2018 and 2023. Participants received DFPP (median 3–5 sessions), either alone or combined with immunotherapies. The primary outcome was neurological improvement, measured by the change in modified Rankin Scale (ΔmRS). Secondary outcomes included symptomatic change (ΔCASE score), immunological parameter shifts, and adverse events. Subgroup analyses were conducted based on antibody type, treatment timing, and combination therapies.</div></div><div><h3>Results</h3><div>The cohort had a median age of 47 years (IQR: 24–65), with 49.1 % being female. DFPP significantly reduced median mRS scores from 3.00 to 1.00 (<em>p</em> &lt; 0.001) and CASE scores from 3.00 to 1.00 (<em>p</em> &lt; 0.001). The overall functional improvement rate was 71.9 %. Initiation of DFPP within 14 days of symptom onset was associated with significantly higher response rates (100 % vs. 63.6 %, <em>p</em> &lt; 0.05) and greater neurological improvement (<em>p</em> &lt; 0.05). Combination with IVMP or IVIG did not enhance efficacy compared to DFPP alone (<em>p</em> = 0.600). Immunological profiling revealed significant reductions in IgG (77.55 %), IgA (76.11 %), and IgM (79.96 %), along with modulation of lymphocyte subsets and cytokine levels. Adverse events occurred in 28.1 % of patients, predominantly mild catheter-related thrombosis.</div></div><div><h3>Conclusions</h3><div>DFPP is an effective and well-tolerated treatment for autoimmune encephalitis, significantly improving neurological function modulates immune responses.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100318"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219464","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":"Regulatory T cell therapy for Sjögren's disease: From pathogenesis to targeted treatment","authors":"Zhi Feng Sherman Lim ,&nbsp;Alberta Y. Hoi ,&nbsp;Fabien B. Vincent ,&nbsp;Joshua D. Ooi ,&nbsp;Eric F. Morand ,&nbsp;Maureen Rischmueller ,&nbsp;Yi Tian Ting","doi":"10.1016/j.jtauto.2025.100311","DOIUrl":"10.1016/j.jtauto.2025.100311","url":null,"abstract":"<div><div>Sjögren's disease (SjD) is a chronic systemic autoimmune disorder characterised by lymphocytic infiltration of the salivary and lacrimal glands, leading to the hallmark symptoms of dry eyes and dry mouth. Beyond glandular dysfunction, many patients experience systemic complications—including B cell hyperactivity, organ-specific inflammation, and a markedly increased risk of non-Hodgkin lymphoma—that are frequently under-recognised and poorly managed. Current treatments remain largely empirical and symptomatic, with limited efficacy in modifying disease progression or restoring immune tolerance.</div><div>Recent advances have illuminated profound dysregulation in both innate and adaptive immunity, revealing novel therapeutic targets now under investigation in clinical trials, including type I interferon signalling, B cell activation, and co-stimulatory pathways. Central to this dysregulation is T cell–driven pathology: CD8⁺ T cell cytotoxicity, defective regulatory T cell (Treg) function, and HLA class II–mediated presentation of self-antigens to autoreactive CD4⁺ T cells are key mechanisms in disease initiation and persistence.</div><div>A growing body of evidence implicates Ro autoantigens—Ro60 and Ro52—as central targets in SjD pathogenesis. Anti-Ro antibodies are present in approximately 70 % of patients and serve as both diagnostic markers and indicators of systemic involvement. Ro antigens and their corresponding antibodies are consistently detected in inflamed salivary tissues, underscoring their potential as compelling targets for antigen-specific therapy.</div><div>This review examines the immunopathogenic role of Ro-specific T cell responses in SjD and outlines how engineered Treg-based therapies may enable precise immune modulation, restore tolerance, and provide durable disease control for patients with this complex autoimmune condition.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100311"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932219","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":"2025-12-01","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":"Rheumatoid factor and anti-citrullinated protein IgA antibodies in the diagnosis, prognosis and monitoring of patients with rheumatoid arthritis","authors":"Ulrike Steffen ,&nbsp;Daniela Sieghart ,&nbsp;Günter Steiner","doi":"10.1016/j.jtauto.2025.100332","DOIUrl":"10.1016/j.jtauto.2025.100332","url":null,"abstract":"<div><div>Over the past decades immunoglobulin A (IgA) antibodies have gained increasing attention for their diagnostic and prognostic significance in rheumatoid arthritis (RA), complementing the well-established roles of IgM rheumatoid factor (RF) and IgG anti-citrullinated protein antibodies (ACPA). IgA-RF and IgA-ACPA are found in a subset of RA patients and have been associated with more severe disease phenotypes, including increased joint erosion and extra-articular manifestations, especially cardiovascular disease and lung involvement. Moreover, concerning prediction of therapeutic responses IgA isotypes seem to have potential, as their presence has been shown to be associated with a blunted response to treatment with TNF inhibitors suggesting their usefulness for disease monitoring during follow-up once a diagnosis has been established. Although the diagnostic value of IgA autoantibodies in identifying seronegative RA cases is limited, their presence confirms a diagnosis of RA and may be helpful in the preclinical detection of individuals at risk for developing RA.</div><div>Increasing evidence suggests that IgA-RF and IgA-ACPA may contribute to disease pathogenesis. They can activate myeloid cells through engagement with the Fc alpha receptor I, leading to enhanced pro-inflammatory cytokine release, phagocytosis, and the formation of neutrophil extracellular traps that exacerbate tissue damage. Taken together, measuring IgA isotypes may be considered a valuable addition to the serological armamentarium for RA, with potential to improve early diagnosis, risk stratification, and personalized therapeutic approaches.</div><div>This review summarizes the current knowledge regarding the value of IgA-RF and IgA-ACPA as diagnostic and prognostic markers for RA. In addition, we discuss how the presence of IgA autoantibodies fits into the mucosal origin theory and describe their potential pathologic effects.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100332"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568201","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":"Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint","authors":"Georgios K. Vasileiadis ,&nbsp;Yuan Zhang ,&nbsp;Marion Laudette ,&nbsp;Tahzeeb Fatima ,&nbsp;Anna-Karin Hultgård Ekwall ,&nbsp;Reshmi Sureshkumar ,&nbsp;Ronald van Vollenhoven ,&nbsp;Jon Lampa ,&nbsp;Bjorn Gudbjornsson ,&nbsp;Espen A. Haavardsholm ,&nbsp;Dan Nordström ,&nbsp;Gerdur Gröndal ,&nbsp;Kim Hørslev-Petersen ,&nbsp;Kristina Lend ,&nbsp;Merete L. Hetland ,&nbsp;Michael Nurmohamed ,&nbsp;Mikkel Østergaard ,&nbsp;Till Uhlig ,&nbsp;Tuulikki Sokka-Isler ,&nbsp;Anna Rudin ,&nbsp;Cristina Maglio","doi":"10.1016/j.jtauto.2025.100310","DOIUrl":"10.1016/j.jtauto.2025.100310","url":null,"abstract":"<div><h3>Objective</h3><div>In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) alter their metabolism to support their activation. We aimed to analyse the full spectrum of metabolic alterations associated with RA by performing untargeted metabolomics in RA FLS vs. non-inflamed (NI) FLS.</div></div><div><h3>Methods</h3><div>Untargeted annotated metabolomics was performed using mass spectrometry on ten primary RA and seven NI FLS culture extracts and 220 serum samples from participants with early RA from the randomised controlled NORD-STAR trial. Carnitine-related proteins were measured with Western blot. FLS bioenergetic profile was assessed with a Seahorse flux analyser.</div></div><div><h3>Results</h3><div>Metabolomics analysis based on 138 annotated metabolites revealed a distinct metabolic fingerprint between RA and NI FLS. Of the 12 metabolites enriched in RA FLS, 11 were acylcarnitines. Pro-inflammatory stimulation of NI FLS also led to acylcarnitine accumulation. RA FLS exhibited lower levels of CD36, a fatty acid transporter, but similar levels of L-carnitine transporter, and carnitine palmitoyltransferase 1 A and 2 compared to NI FLS. Seahorse analyses showed no difference in fatty acid oxidation between RA and NI FLS; however, RA FLS displayed mitochondrial dysfunction and energetic impairment. Serum acylcarnitine content decreased after 24 weeks of treatment with methotrexate combined with abatacept or tocilizumab in patients with early RA achieving remission.</div></div><div><h3>Conclusion</h3><div>Acylcarnitine accumulation is a characteristic of RA FLS metabolic fingerprint and could be linked to mitochondrial dysfunction. In patients with early RA, acylcarnitine content in serum decreases after successful anti-rheumatic treatment. These results indicate a dysregulation in acylcarnitine metabolism in RA at the joint level and systemically.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100310"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878752","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}