Julia Minnee , Jorge Cuenca-Escalona , Johanna Bödder , Georgina Flórez-Grau , Esther C. de Jong , I. Jolanda M. de Vries
{"title":"Vitamin D3 encapsulated in polymeric nanoparticles to dampen the pro-inflammatory immune response","authors":"Julia Minnee , Jorge Cuenca-Escalona , Johanna Bödder , Georgina Flórez-Grau , Esther C. de Jong , I. Jolanda M. de Vries","doi":"10.1016/j.jtauto.2025.100321","DOIUrl":"10.1016/j.jtauto.2025.100321","url":null,"abstract":"<div><div>1α25-dihydroxyvitamin D3, the active metabolite of vitamin D3 (VD3), is a modulator of inflammation well-known for its ability to promote anti-inflammatory and tolerogenic immune responses. It is therefore an attractive agent for the attenuation of inflammatory responses and the development of tolerogenic immunity in autoimmune diseases. To overcome VD3 toxicity and enhance its <em>in vivo</em> performance, nanoparticles (NPs) have emerged as a promising delivery platform. Therefore, in this study, we have developed VD3-loaded polymeric nanoparticles (VD3-NPs) as a therapeutical strategy for the treatment of autoimmune disorders. We demonstrate that VD3-NPs could successfully be generated and that they significantly inhibit secretion of IL-6, IL-10, IL-23, and TNFα in human whole blood cultures. We observed that poly(lactic-co-glycolic acid) (PLGA) NPs are efficiently taken up by neutrophils, monocytes and B cells, prompting further investigation into the effect of VD3-NPs on these subsets. Investigation into each of the immune cell subsets demonstrated that the VD3-NPs were able inhibit cytokine secretion by both monocytes and neutrophils. Moreover, VD3-NPs induced a tolerogenic phenotype in monocytes. In B cells, we observed that VD3-NPs impaired <em>in vitro</em> plasma B cell differentiation and suppressed antibody production. Together, our results validate for the first time in primary human cells the therapeutic potential of VD3 encapsulated in PLGA NPs, posing an attractive strategy for the treatment of autoimmune diseases.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100321"},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219465","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}
Yan Gao , Xinge Li , Fengting Luo , Ruibing Chen , Xiangyang Zhang
{"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 , Xinge Li , Fengting Luo , Ruibing Chen , 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":"2025-09-24","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}
Hongyan Li , Kan Wang , Qiuju Li , Xuzhong Pei , Jie Ding , Jing Peng , Wanwan Li , Xiajun Zhou , Desheng Zhu , Yangtai Guan
{"title":"Clinical efficacy and immunomodulation of double-filtration plasmapheresis in autoimmune encephalitis: A prospective study highlighting the importance of timely initiation","authors":"Hongyan Li , Kan Wang , Qiuju Li , Xuzhong Pei , Jie Ding , Jing Peng , Wanwan Li , Xiajun Zhou , Desheng Zhu , 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> < 0.001) and CASE scores from 3.00 to 1.00 (<em>p</em> < 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> < 0.05) and greater neurological improvement (<em>p</em> < 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":"2025-09-23","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}
Klara Martinsson , Simon Åhammar , Alexandra Cîrciumaru , Bence Réthi , Michael Ziegelasch , Aase Hensvold , Alf Kastbom
{"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 , Simon Åhammar , Alexandra Cîrciumaru , Bence Réthi , Michael Ziegelasch , Aase Hensvold , 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 < 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 < 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":"2025-09-17","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}
Choa Yun , Dongwon Yoon , Sun Young Jung , Moonsuk Kim , May A. Beydoun , Lenore Launer , Minkyo Song
{"title":"Immune responses to infection and autoimmune diseases in the UK biobank","authors":"Choa Yun , Dongwon Yoon , Sun Young Jung , Moonsuk Kim , May A. Beydoun , Lenore Launer , 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 < 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":"2025-09-17","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}
Aimei Pang , Shuangshuang Pu , Yinghui Pan , Ning Huang , Dake Li
{"title":"Short-chain fatty acids from gut microbiota restore Th17/Treg balance in rheumatoid arthritis: Mechanisms and therapeutic potential","authors":"Aimei Pang , Shuangshuang Pu , Yinghui Pan , Ning Huang , Dake Li","doi":"10.1016/j.jtauto.2025.100316","DOIUrl":"10.1016/j.jtauto.2025.100316","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction. Dysregulation of the Th17/Treg balance is a key immunological hallmark of RA. Emerging evidence highlights the critical role of gut microbiota-derived short-chain fatty acids (SCFAs) in maintaining immune homeostasis. This review systematically elucidates how SCFAs modulate the Th17/Treg equilibrium through three synergistic mechanisms: (1) metabolic reprogramming via AMPK/mTOR signaling, (2) epigenetic regulation by inhibiting HDAC, and (3) modulation of cytokine cascades. We integrate preclinical and clinical evidence showing that SCFAs reduce synovial inflammation by suppressing NLRP3 inflammasome activation, resulting in a 70 % decrease in IL-1β levels, while enhancing Treg suppressive function with a threefold increase in IL-10. Notably, butyrate exhibits circadian fluctuations that negatively correlate with morning stiffness severity (r = −0.82, p < 0.01), suggesting novel chronotherapeutic opportunities. Therapeutically, we evaluate promising microbiota-targeted strategies including high-fiber diets (which increase butyrate levels by 240 % and reduce Disease Activity Score 28 (DAS28) by 1.8 points), engineered nanoparticle delivery systems (achieving 89 % colonic retention), probiotic interventions (Bifidobacterium-mediated reduction of CCR9-positive Th17 cells), and precision combination therapies (showing a 40 % greater efficacy than monotherapy). Our work establishes a comprehensive translational roadmap, spanning molecular insights to clinical applications. We propose microbiome-guided personalized medicine as a paradigm shift in RA management, supported by the first systematic integration of multi-omics methods-metabolomics, single-cell sequencing, and spatial transcriptomics-to decode the gut-joint axis and identify actionable therapeutic targets for this refractory autoimmune condition.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100316"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095272","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":"Cell-specific epigenome-wide DNA methylation in peripheral CD4(+) lymphocytes from patients with primary biliary cholangitis","authors":"Pinelopi Arvaniti , Kalliopi Zachou , Aggeliki Lyberopoulou , Eirini Sevdali , Stella Gabeta , Matthaios Speletas , Yves Renaudineau , George N. Dalekos","doi":"10.1016/j.jtauto.2025.100314","DOIUrl":"10.1016/j.jtauto.2025.100314","url":null,"abstract":"<div><h3>Background/aims</h3><div>Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease, triggered by a complex interplay between genetic, environmental and epigenetic factors. We investigated the methylation profile of peripheral CD4(+) lymphocytes from PBC patients compared to healthy controls (HC) and autoimmune hepatitis (AIH) patients, to elucidate gene specific epigenetic modifications that contribute to PBC pathogenesis, as similar data are limited.</div></div><div><h3>Methods</h3><div>CD4(+) lymphocytes were isolated from 8 PBC treatment-naïve patients, 9 HC and 10 AIH patients at diagnosis by ROBOSEP platform. Whole genome methylation analysis was performed by 850k array of Illumina. Candidate genes’ transcriptional expression was quantified by RT-PCR.</div></div><div><h3>Results</h3><div>Comparison between PBC patients and HC, revealed 1016 differentially methylated positions (DMPs) on autosomal chromosomes and 1203 DMPs on X chromosome (>98 % hypermethylated), corresponding to 695 and 322 genes, respectively (p < 0.05). Hypermethylation mainly affected pathways of immune cells differentiation and signalling (CAMTA1, PRKARB, LNC01993, TLR9)<em>.</em> Methylation analysis between PBC and AIH revealed >5000 DMPs (98 % hypermethylated in PBC) corresponding to >4000 genes. Pathway analysis retrieved an enrichment of “cytokine” and “interleukin” signalling (C1GTNF3, SMAD3). Analysis of differentially methylated regions showed enrichment on gene promoters and hypermethylation of IFN-regulated genes (IFNGR2, TICAM2) in PBC patients. Genes expression at the transcriptional level showed over-expression of IFNGR2 in PBC patients.</div></div><div><h3>Conclusions</h3><div>Hypermethylation characterizes most genes of peripheral CD4(+) lymphocytes in PBC. The epigenetic modifications mainly affect pathways of immunological responses. The significant number of X chromosome located DMPs, further supports the role of sex in PBC pathogenesis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100314"},"PeriodicalIF":3.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044686","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":"Splicing-based biomarkers define a robust multigene classifier for relapsing-remitting multiple sclerosis","authors":"Federica Airi , Valeria Rimoldi , Elvezia Maria Paraboschi , Valentina Pellicanò , Damiano Verda , Giuseppe Liberatore , Claudia Cantoni , Laura Piccio , Alvino Bisecco , Anita Capalbo , Giulia Cardamone , Eduardo Nobile-Orazio , Giulia Soldà , Rosanna Asselta","doi":"10.1016/j.jtauto.2025.100312","DOIUrl":"10.1016/j.jtauto.2025.100312","url":null,"abstract":"<div><h3>Background</h3><div>Alternative splicing (AS) is recognized as a key mechanism in multiple sclerosis (MS). We aimed to construct and validate a multivariate AS-based classifier (MS-Splicing Score, MS-SS) for the discrimination of relapsing-remitting MS (RRMS) patients from healthy controls.</div></div><div><h3>Methods</h3><div>Three AS events (<em>IFNAR2</em> exon-8 skipping, <em>NFAT5</em> exon-2 skipping, <em>PRKCA</em> exon-3∗ inclusion) were selected based on functional and literature evidence. Isoforms were quantified via fluorescent-competitive RT-PCR in peripheral blood RNA from two independent cohorts (Italy: 37 RRMS, 50 controls; USA: 29 RRMS, 20 controls). A logistic regression model was trained to derive the MS-SS, followed by ROC analysis.</div></div><div><h3>Results</h3><div>The MS-SS distinguished RRMS patients from controls in both cohorts (Italy: p = 0.00083, AUC = 0.71, 95 %CI = 0.59–0.82; USA: p = 0.00074, AUC = 0.77, 95 %CI = 0.63–0.90). In the pooled dataset, the score remained significantly elevated in MS (p = 5.9 × 10<sup>−6</sup>, AUC = 0.72, 95 %CI = 0.64–0.81), and a PCA-based refinement improved classification accuracy, yielding an AUC = 0.87 (95 %CI = 0.81–0.94). At the optimal cutoff (Youden's index), the score achieved a sensitivity of 80 % and specificity of 86 %. Supervised rule-based modeling using a logic-learning machine algorithm identified interpretable splicing thresholds and enabled clinical classification at the individual level.</div></div><div><h3>Conclusion</h3><div>Our study introduces a novel, robust AS-based classifier for RRMS and proposes a strategy for transcriptome-based biomarker development in neuroimmunology. However, the relatively small sample sizes within each cohort may limit the generalizability of these findings, warranting larger validation studies to confirm the clinical utility of this biomarker.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100312"},"PeriodicalIF":3.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019063","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}
Shan Xu , Christina James Thomas , Sunilgowda Sunnagatta Nagaraja , Rakesh Kumar , Kamlesh Sawant , Duminduni Hewa Angappulige , Andy Fang Song , Krish Suman , Benjamin Borja , Paul de Figueiredo , Jianxun Song
{"title":"Redefining multiple sclerosis therapy through microbial immunomodulation and epigenetic control","authors":"Shan Xu , Christina James Thomas , Sunilgowda Sunnagatta Nagaraja , Rakesh Kumar , Kamlesh Sawant , Duminduni Hewa Angappulige , Andy Fang Song , Krish Suman , Benjamin Borja , Paul de Figueiredo , Jianxun Song","doi":"10.1016/j.jtauto.2025.100313","DOIUrl":"10.1016/j.jtauto.2025.100313","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune disorder marked by immune-driven demyelination and neurodegeneration in the central nervous system. This Review explores the immunological, molecular, and epigenetic underpinnings of MS, emphasizing T and B cell involvement, dysregulated signaling pathways (e.g., TGF-β, Akt, Wnt), and the role of cell death in disease progression. Epigenetic mechanisms—such as DNA methylation and histone modifications, further modulate immune responses. While current therapies broadly suppress immunity, emerging approaches, including engineered bacteria, microbiome-based interventions, and cell therapies, offer targeted immune modulation and neuroprotection. Together, these strategies illuminate a path toward next-generation MS treatments with improved precision and efficacy.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100313"},"PeriodicalIF":3.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988322","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":"Beyond conventional treatment: Novel cell therapies for systemic lupus erythematosus","authors":"Zeinab Zarei-Behjani , Arghavan Hosseinpouri , Maryam Fotoohi , Akram Shafiee , Dorna Asadi","doi":"10.1016/j.jtauto.2025.100308","DOIUrl":"10.1016/j.jtauto.2025.100308","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by its heterogeneity, as it can affect various organs and exhibit a diverse clinical progression. The identification of SLE relies on the presence of distinct clinical manifestations in the skin, joints, kidneys, and the central nervous system, along with serological markers like antinuclear antibodies such as antibodies targeting dsDNA. The present therapeutic approaches for SLE encompass the use of antimalarial agents, glucocorticoids, immunosuppressive medications, and biological therapies. Despite the advancements in therapeutic strategies, SLE continues to be linked with adverse outcomes. The complicity and unpredictable nature of disease, characterized by episodes of relapses and remissions, coupled with the side effects of current treatment options, the progressive accumulation of organ damage, and persistent mortality rates despite therapeutic improvements, underscores the urgent necessity for the creation of innovative, effective, and specifically targeted therapies. Cell-based therapies, although still in their nascent stages, have attracted considerable interest in the realm of SLE treatment due to their potential for long-term disease suppression or even the possibility of a cure. Various cell types have emerged as promising candidates for SLE management. This review aims to provide a brief overview of the most recent research on novel cell-based therapeutic approaches that have progressed to either pre-clinical or clinical trial phases for the treatment of SLE.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100308"},"PeriodicalIF":3.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932217","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}