Rosanna Di Paola, Roberta Fusco, Daniela Impellizzeri, Marika Cordaro, Domenico Britti, Valeria Maria Morittu, Maurizio Evangelista, Salvatore Cuzzocrea
{"title":"Editorial expression of concern: Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats.","authors":"Rosanna Di Paola, Roberta Fusco, Daniela Impellizzeri, Marika Cordaro, Domenico Britti, Valeria Maria Morittu, Maurizio Evangelista, Salvatore Cuzzocrea","doi":"10.1186/s13075-026-03856-0","DOIUrl":"10.1186/s13075-026-03856-0","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenping Pan, Liguo Yin, Lantao Wang, Qing Wang, Tingting Zhai, Jin Cao, Xia Wang, Hongsheng Sun
{"title":"Evaluating clinical heterogeneity in relapsing polychondritis through unsupervised cluster analysis.","authors":"Wenping Pan, Liguo Yin, Lantao Wang, Qing Wang, Tingting Zhai, Jin Cao, Xia Wang, Hongsheng Sun","doi":"10.1186/s13075-026-03857-z","DOIUrl":"10.1186/s13075-026-03857-z","url":null,"abstract":"<p><strong>Background: </strong>As a rare autoimmune disease, relapsing polychondritis (RP) exhibits individual variations in clinical manifestations, treatment response and prognosis. To date, no biomarkers have been implemented to clinical practice.This study aimed to apply cluster analysis to identify the clinical phenotype, clarify their prognosis predictor, and monitor treatment decisions to improve the outcomes of patients.</p><p><strong>Methods: </strong>A total of 135 RP patients hospitalized in two centers from January 2005 to December 2024 were involved in the study.The K-means clustering algorithm was used as the core clustering tool. The optimal number of clusters(K = 3)was determined through comprehensive evaluation using the Elbow Method and Silhouette Analysis.</p><p><strong>Results: </strong>Cluster analysis identified 3 RP phenotypes.Cluster 1 comprised 45 cases(33.3%),characterized by a hyperinflammatory state and predominant respiratory involvement; Cluster 2 included 11 cases (8.1%),defined by severe and multi-organ involvement Cluster 3 which accounted for 79 cases (58.52%), more than half of the cohort, was predominantly male and exhibited the most favorable prognosis.In contrast, Clusters 1 and 2 were associated with the highest rates of clinical deterioration.</p><p><strong>Conclusions: </strong>This study confirms that relapsing polychondritis is not a single-dimensional disease, but a clinical syndrome with significant heterogeneity. Random forest analysis further identifies that systemic inflammation markers (CRP, CAR, ESR) and sensory organ involvement (hearing impairment and inner ear dysfunction) as the most critical driving factors for distinguishing these subtypes.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tim Filla, Alexandru Micu, Lasse Hansen, Isabel Grinberg, Franca Sophie Deicher, Laura-Marie Lahu, Alexandru-Emil Matei, Christina Düsing, Gabriela Riemekasten, Norbert Blank, Annette Alberding, Marc Schmalzing, Jan Ehrchen, Claudia Günther, Gabriele Zeidler, Ilona Jandova, Gernot Keyßer, Margitta Worm, Ulf Müller-Ladner, Aaron Juche, Laura Susok, Peter Korsten, Jörg Henes, Alexander Kreuter, Pia Moinzadeh, Thomas Krieg, Marielle Girke, Margarida Alves, Nicolas Hunzelmann, Jörg H W Distler, Andrea-Hermina Györfi
{"title":"Real-world treatment patterns and determinants of therapy in systemic sclerosis: findings from the German Network for SSc cohort.","authors":"Tim Filla, Alexandru Micu, Lasse Hansen, Isabel Grinberg, Franca Sophie Deicher, Laura-Marie Lahu, Alexandru-Emil Matei, Christina Düsing, Gabriela Riemekasten, Norbert Blank, Annette Alberding, Marc Schmalzing, Jan Ehrchen, Claudia Günther, Gabriele Zeidler, Ilona Jandova, Gernot Keyßer, Margitta Worm, Ulf Müller-Ladner, Aaron Juche, Laura Susok, Peter Korsten, Jörg Henes, Alexander Kreuter, Pia Moinzadeh, Thomas Krieg, Marielle Girke, Margarida Alves, Nicolas Hunzelmann, Jörg H W Distler, Andrea-Hermina Györfi","doi":"10.1186/s13075-026-03854-2","DOIUrl":"10.1186/s13075-026-03854-2","url":null,"abstract":"<p><strong>Objectives: </strong>Therapeutic management of systemic sclerosis (SSc) has evolved considerably in recent years. However, contemporary treatment patterns and prescribing determinants remain poorly characterized.</p><p><strong>Methods: </strong>Data from the German Network for SSc (DNSS) cohort containing 6,583 patients were analyzed to describe trends in vasoactive, immunomodulatory, and antifibrotic therapy; assess variation between centers and specialties; delineate co-prescription patterns; and identify clinical predictors of treatment.</p><p><strong>Results: </strong>Use of endothelin receptor antagonists and prostanoids / prostacyclin receptor agonists increased from 3.0% [95% confidence interval (CI): 1.5%-5.3%] in 2005 to 28.4% [25.5%-31.3%] in 2025, whereas prescription of calcium channel blockers and phosphodiesterase-5 inhibitors remained stable. Immunomodulatory therapy shifted away from cyclophosphamide towards mycophenolate mofetil, rituximab, and nintedanib, accompanied by a marked decline in glucocorticoid use (50.0% [31.9%-68.1%] in 2000 to 18.1% [11.8%-25.9%] in 2025). University or rheumatology centers prescribed immunomodulators and antifibrotics more frequently than non-university or dermatology centers. Co-prescription patterns showed common combination therapy with tocilizumab or rituximab and methotrexate. Nintedanib was commonly co-administered with mycophenolate, but also with cyclophosphamide or methotrexate. Rituximab was most commonly combined with mycophenolate and tocilizumab with methotrexate. Multivariable mixed models identified modified Rodnan skin score, interstitial lung disease, heart involvement, and care in a university, particularly rheumatology, center as major determinants of immunomodulatory and antifibrotic therapy.</p><p><strong>Conclusions: </strong>SSc treatment has evolved over the past 25 years, with prescribing patterns increasingly reflecting evidence and guideline recommendations. However, differences between specialties and care settings highlight the need for broader implementation of multidisciplinary, guideline-based care.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DAS28-ESR may underestimate disease activity in rheumatoid arthritis patients with nonalcoholic fatty liver disease: a retrospective cohort study.","authors":"Yutaka Shinkawa, Masao Tanaka, Tomoya Nakajima, Masashi Taniguchi, Kyosuke Fukumori, Kayo McCracken, Mori Masato, Tomomi Sato-Nakamura, Takuji Nakamura, Shinji Hirose, Akio Morinobu, Hisanori Umehara","doi":"10.1186/s13075-026-03858-y","DOIUrl":"10.1186/s13075-026-03858-y","url":null,"abstract":"<p><strong>Background: </strong>Although approximately one-third of patients with rheumatoid arthritis (RA) have comorbid nonalcoholic fatty liver disease (NAFLD), the clinical characteristics of these patients remain unclear. The aim of this study was to clarify the clinical characteristics of RA patients classified as having NAFLD based on imaging, with a focus on composite disease activity assessment.</p><p><strong>Methods: </strong>This retrospective cohort study analysed data from 349 RA patients enrolled in the Nagahama Riumachi Cohort between March 2017 and August 2023. Patients with liver diseases other than NAFLD were excluded. NAFLD was classified based on findings from abdominal computed tomography and/or ultrasonography performed during the cohort period. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). Functional status was evaluated using the Health Assessment Questionnaire Disability Index (HAQ-DI). Factors associated with NAFLD were examined by logistic regression, and repeated measurements during follow-up were analysed using linear mixed-effects models.</p><p><strong>Results: </strong>Seventy-three patients (20.9%) were classified as having NAFLD and 276 (79.1%) as not having NAFLD. Patients in the NAFLD group were younger, had a higher proportion of men, and had a higher prevalence of body mass index (BMI) ≥ 25 kg/m². There were no significant differences between the groups in disease activity assessed by CDAI, SDAI, or DAS28-CRP. However, the NAFLD group had significantly lower DAS28-ESR and erythrocyte sedimentation rate (ESR) values despite similar C-reactive protein (CRP) levels. HAQ-DI was lower in the NAFLD group, especially in the lower-limb domain. In multivariable analysis, younger age and higher (BMI) were independently associated with NAFLD, but ESR and HAQ-DI were not significantly associated. In linear mixed-effects models, NAFLD classification was not significantly associated with ESR, although ESR tended to be lower in the NAFLD group.</p><p><strong>Conclusions: </strong>Among patients with RA classified as having NAFLD, DAS28-ESR may underestimate disease activity compared with CRP-based or clinical indices. In these patients, DAS28-CRP, CDAI, and SDAI may provide complementary information.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential gene expression of retrotransposons (LTR and non-LTR) in peripheral blood leukocytes of people with gout.","authors":"Ya-Sian Chang, Ming-Hon Hsu, Chieh-Min Chang, Ta-Chih Liu, Jan-Gowth Chang","doi":"10.1186/s13075-026-03860-4","DOIUrl":"10.1186/s13075-026-03860-4","url":null,"abstract":"<p><strong>Background: </strong>To investigate the expression profiles of retrotransposons in people with gout and their clinical significance.</p><p><strong>Methods: </strong>Peripheral blood leukocytes from 92 people with gout and 22 healthy controls were analyzed using Telescope and TEspeX to quantify human endogenous retroviruses (HERVs) and non-long terminal repeat (non-LTR). Gene Set Variation Analysis (GSVA) was used to assess the association of the alterations of HERV and viral related gene panels, and xCell to evaluate the changes of immune cell subpopulations. HEK293 and THP-1 cells were treated with uric acid (UA) and monosodium urate (MSU) to explore and confirm the mechanisms of retrotransposon changes.</p><p><strong>Results: </strong>A total of 238 HERVs and 49 non-LTR were differentially expressed in people with gout as compared to healthy controls. Notably, HERVs exhibited lower expression levels overall, whereas most non‑LTR retrotransposons showed higher expression in people with gout, suggesting distinct immunological triggers. Among 397 genes located near differentially expressed HERVs, several displayed altered expressions, indicating potential locus-specific co-regulation. GSVA revealed that gene panels related to HERV regulation, including nearby genes, KRAB zinc-finger proteins, and stemness-associated genes, were less enriched in gout patients compared to controls. xCell analysis revealed significant changes in immune cell composition, including reduced proportions of neutrophils and NK cells, and increased CD4 + memory T-cells and regulatory T cells, aligning with gout-related immune migration and modulation. Consistent with the transcriptomic data, our cell-based assays demonstrated that UA and MSU differentially modulate LTR and non-LTR retrotransposon expression across distinct cell types.</p><p><strong>Conclusions: </strong>This study reveals a distinct and dynamic retrotransposon signature in gout, with potential implications priming, immune cell behavior, and gene regulation.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucia Vernerová, Lucie Lážnovská, Jiří Baloun, Veronika Balounová, Martina Vokurková, Martin Klein, Zdeněk Verner, Tomáš Kičura, Heřman Mann, Sabína Oreská, Kristina Svobodová, Tereza Kropáčková, Michal Tomčík, Jozef Ukropec, Barbara Ukropcová, Jiří Vencovský
{"title":"Alterations in systemic and skeletal muscle myostatin regulation are most prominent at disease onset and associate with muscle-related outcomes in idiopathic inflammatory myopathies.","authors":"Lucia Vernerová, Lucie Lážnovská, Jiří Baloun, Veronika Balounová, Martina Vokurková, Martin Klein, Zdeněk Verner, Tomáš Kičura, Heřman Mann, Sabína Oreská, Kristina Svobodová, Tereza Kropáčková, Michal Tomčík, Jozef Ukropec, Barbara Ukropcová, Jiří Vencovský","doi":"10.1186/s13075-026-03847-1","DOIUrl":"10.1186/s13075-026-03847-1","url":null,"abstract":"<p><strong>Background: </strong>Recent findings indicate attenuated myostatin (MSTN) signalling in idiopathic inflammatory myopathies (IIM) and an inverse association between circulating MSTN and disease activity. The temporal and mechanistic relationship of these alterations to disease pathogenesis remains unclear. We therefore investigated systemic and skeletal muscle MSTN regulation in newly diagnosed patients at disease onset, after six months of therapy, and in chronic IIM.</p><p><strong>Methods: </strong>A total of 101 patients with IIM and 134 healthy controls (HC) were enrolled. Muscle biopsies were obtained from 59 newly diagnosed untreated or shortly treated patients, 19 patients after six months of therapy, 19 chronic IIM patients, and 21 HC. Serum samples and clinical data were collected during routine visits. Circulating MSTN, follistatin (FST), follistatin-like 3 (FSTL3) and activin A (ActA) were measured by ELISA. mRNA and protein expression of MSTN pathway components in muscle tissue were assessed by qPCR (TaqMan<sup>®</sup>) and immunoblotting. Associations of serum MSTN, FST, FSTL3 and ActA with clinical outcomes were analysed using linear mixed-effects models (LMM) and partial least squares regression during the first six months of therapy.</p><p><strong>Results: </strong>Newly diagnosed IIM patients had significantly lower circulating MSTN and higher FST levels than chronic patients and HC, whereas ActA was elevated only in chronic disease. After normalization to body cell mass, MSTN remained reduced in newly diagnosed patients and increased after six months of therapy, while FST, ActA and FSTL3 did not change significantly. LMM analysis demonstrated strong associations of FSTL3 with systemic inflammation, disease activity and reduced physical and mental health scores, predominantly in female patients. In muscle tissue, newly diagnosed patients showed increased expression of MSTN pathway genes and proteins, including MSTN, SMAD2/3 and ubiquitin-proteasome components. Multivariate analyses integrating clinical, biochemical and molecular parameters identified a latent component linking MSTN pathway activation with muscle disease activity.</p><p><strong>Conclusion: </strong>Early IIM is characterized by dissociation between reduced circulating MSTN and activation of MSTN signalling in skeletal muscle, which diminishes with treatment and disease chronicity. Circulating FSTL3 is associated with systemic inflammation, disease activity and patient-reported outcomes, with pronounced associations in female patients. These findings highlight stage- and sex-dependent alterations of the MSTN regulatory network in IIM.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Seidlberger, S Castañeda, G Wietzorrek, K Faserl, A Triguero-Martínez, A González-García, M Schirmer, S Santos-Sierra
{"title":"Plasma proteome differences between giant cell arteritis and polymyalgia rheumatica: a pilot study.","authors":"S Seidlberger, S Castañeda, G Wietzorrek, K Faserl, A Triguero-Martínez, A González-García, M Schirmer, S Santos-Sierra","doi":"10.1186/s13075-026-03852-4","DOIUrl":"10.1186/s13075-026-03852-4","url":null,"abstract":"<p><strong>Background: </strong>Giant cell arteritis (GCA) is the most prevalent vasculitis in the elderly of Caucasian ancestry, with the risk of visual loss as the most serious complication if the glucocorticoid therapy does not succeed. While imaging and temporal artery biopsy (TAB) remain diagnostic gold standards, new laboratory tests are needed to assess disease activity and follow-up monitoring.</p><p><strong>Objective: </strong>We aimed to characterize distinct proteomic signatures for the classification of polymyalgia rheumatica (PMR) and GCA (independent of concurrent therapy) and to identify specific markers of disease activity and markers that differentiate the two diseases.</p><p><strong>Methods: </strong>The plasma of 15 PMR and 13 GCA patients was analysed via mass spectrometry with the UltiMate 3000 nano-HPLC system coupled to an Orbitrap Eclipse mass spectrometer. Immunofluorescence analyses in TABs were performed to confirm the elevated plasma expression of S100A12.</p><p><strong>Results: </strong>We identified 50 protein signatures characteristic of active GCA patients, and 83 signatures altered only in active PMR samples. Strikingly, both groups shared only 13 proteins with altered protein expression levels. The newly identified proteins point to activation of biological pathways not yet linked to the diseases: mitochondrial membrane activity (ACACA, SLC25A31) and clotting cascade (VWF, TUBB) in active GCA; erythrocyte integrity (SLC4A1, SPTA1), muscle contraction (MYLK, MYL6B/12B), and glucocorticoid resistance (PTGES3) in active PMR. Importantly, S100A12 was increased not only in plasma (~ 1.6-fold), but also in PMR and GCA TABs.</p><p><strong>Conclusion: </strong>Active PMR and active GCA patients share an unexpectedly small plasma proteome signature related to immune activation (8.9%: 13 proteins). Instead, active PMR is characterized by distinct erythrocyte and muscle contraction proteome changes, whereas active GCA appears driven by mitochondrial and clotting cascade alterations. Prospective, longitudinal validation studies of the described proteomic signatures might support the clinical classification of both diseases.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofei Luo, Xuchang Zhou, Yuehui Wang, Zhe Li, Xier Chen, Xuan Wei, Guoxin Ni
{"title":"Elucidating the mechanism of taurine in alleviating osteoarthritis progression based on bioinformatics, machine learning algorithm, and experimental validation.","authors":"Xiaofei Luo, Xuchang Zhou, Yuehui Wang, Zhe Li, Xier Chen, Xuan Wei, Guoxin Ni","doi":"10.1186/s13075-026-03844-4","DOIUrl":"10.1186/s13075-026-03844-4","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, plays a pivotal role in chondrocyte death and the pathogenesis of osteoarthritis (OA). Taurine, a sulfur-containing amino acid with established anti-inflammatory and anti-ferroptotic properties, has been implicated in joint protection; however, its potential to mitigate OA progression by targeting ferroptosis mechanisms remains largely unexplored.</p><p><strong>Methods: </strong>RNA sequencing was performed on normal and OA knee joint cartilage tissues to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was used to screen for OA-related modules, and ferroptosis-related targets were retrieved from public databases. Intersecting genes from the DEGs, WGCNA modules, and ferroptosis targets underwent pathway enrichment analysis. Taurine target genes were predicted via multiple databases, and machine learning algorithms were applied to identify hub genes. A nomogram model was constructed to evaluate diagnostic accuracy. Immune infiltration was assessed using the CIBERSORT algorithm. Furthermore, in vitro experiments involving interleukin-1 beta (IL-1β)-stimulated chondrocytes and in vivo studies using a destabilization of the medial meniscus (DMM) mouse model were conducted to validate the effects of taurine.</p><p><strong>Results: </strong>Machine learning analysis identified four key hub genes: CSRNP1, CTH, OSBPL3, and CITED2. CTH was selected as the primary focus due to the effect of taurine on its expression in IL-1β-stimulated chondrocytes. In vitro assays demonstrated that taurine treatment specifically reversed the IL-1β-induced downregulation of CTH. Mechanistic studies showed that taurine directly bound to the CTH protein and attenuated IL-1β-induced ferroptosis by restoring CTH expression, thereby increasing glutathione (GSH) levels, reducing iron accumulation and lipid peroxidation, and upregulating solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Consistently, taurine alleviated cartilage degradation and synovial inflammation in DMM-induced OA mice, whereas these benefits were reversed by the CTH inhibitor propargylglycine (PAG).</p><p><strong>Conclusion: </strong>Taurine exerted significant chondroprotective effects, at least in part, by directly targeting CTH to suppress chondrocyte ferroptosis, thereby ameliorating OA progression.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Le Qiang, Nan Wang, Yuhan Jia, Jiahui Xue, Yue Jin, Lei Sun, Xiaohan Ni, Yanlin Wang, Min Feng, Chong Gao, Jing Luo
{"title":"Discovery of biomarkers for primary Sj ögren's syndrome based on multi-omics data, construction of diagnostic models, and clinical correlation analysis.","authors":"Le Qiang, Nan Wang, Yuhan Jia, Jiahui Xue, Yue Jin, Lei Sun, Xiaohan Ni, Yanlin Wang, Min Feng, Chong Gao, Jing Luo","doi":"10.1186/s13075-026-03855-1","DOIUrl":"10.1186/s13075-026-03855-1","url":null,"abstract":"<p><strong>Objective: </strong>Primary Sjogren's syndrome(pSS) exhibits significant clinical heterogeneity, which poses challenges for accurately assessing disease activity, predicting organ involvement, and diagnosing seronegative patients(SNSS). This study aimed to delineate the metabolic landscape of pSS by integrating metabolomic, lipidomic, and multi-dimensional clinical data to identify novel biomarkers for these purposes and to uncover the intrinsic links between metabolic dysregulation and immune dysfunction.</p><p><strong>Methods: </strong>Untargeted metabolomic and lipidomic analyses were performed on plasma samples from a discovery cohort and an independent validation cohort. A machine learning-based metabolic model was developed using selected features, and its diagnostic performance was evaluated by receiver operating characteristic curve (ROC) analysis.</p><p><strong>Results: </strong>Compared with healthy controls(HC), pSS patients exhibited significant alterations in 65 metabolites from the metabolomic analysis and 63 lipids from the lipidomic analysis, indicating systemic metabolic pathway disruptions.Network analysis revealed extensive correlations of metabolomic/lipidomic profiles with clinical parameters and immune cell subsets. A panel of four biomarkers was identified and validated, demonstrating high efficacy in distinguishing SNSS. Furthermore, the levels of redox-related metabolites were significantly associated with age, sex, and anti-SSA antibody status. Seven biomarkers showed significant correlations with the EULAR Sjögren's Syndrome Disease Activity Index(ESSDAI). Specific metabolic signatures were also identified for different organ involvement phenotypes, achieving AUC values of 0.763 and 0.871 for predicting pulmonary and hematological involvement, respectively.</p><p><strong>Conclusion: </strong>This study systematically defines specific metabolic features of pSS, establishes a validated diagnostic model for SNSS, and confirms the close association between metabolic disturbances and clinical heterogeneity. The findings provide novel metabolic biomarkers and insights for the precise diagnosis and management of pSS.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of distinct subgroups in Chinese patients with Behçet's syndrome via cluster analysis of immune cells and clinical features.","authors":"Jiachen Li, Shanzhao Jin, Feng Sun, Miao Shao, Xia Zhang, Wenhao Lin, Xiao Tan, Xiumei Yang, Xiaolin Sun, Yaping Luo, Zhanguo Li, Tian Liu","doi":"10.1186/s13075-026-03851-5","DOIUrl":"10.1186/s13075-026-03851-5","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to use machine learning to explore Behçet's syndrome (BS) heterogeneity by integrating immunocyte subpopulations and clinical characteristics.</p><p><strong>Methods: </strong>We prospectively enrolled BS patients and recorded their demographic and clinical characteristics. Various peripheral immune cells were analysed using flow cytometry. Unsupervised machine learning was used to perform cluster analysis based on the clinical manifestations and immune cell subsets. Patients were followed up for one year to evaluate treatment response and remission rates. RNA sequencing was performed in patients with clustered BS and healthy controls.</p><p><strong>Results: </strong>Unsupervised machine learning categorized 201 BS patients into four clusters with distinct clinical and immunological features. Cluster 1 showed isolated mucocutaneous lesions, low inflammation, and high remission, with transcriptomic enrichment in IFN-γ, IL-6, and JAK-STAT pathways. Cluster 2 featured arthritis, elevated inflammatory levels, and responded well to TNF-α inhibitors, with transcriptomic enrichment in TNF and B-cell activation pathways. Cluster 3 had cardiovascular involvement, reduced CLA<sup>+</sup> Tregs, and also responded to TNF-α inhibitors, with transcriptomic enrichment in coagulation, platelet activation, and MAPK pathways. Cluster 4 demonstrated neurological involvement, elevated CD161⁺ Tregs, low remission, and a better response to mycophenolate mofetil, with transcriptomic enrichment in T-cell activation and NF-κB pathways.</p><p><strong>Conclusion: </strong>Unsupervised clustering of BS patients revealed four distinct subtypes with significant clinical and immunological heterogeneity, which may provide a foundation for mechanistic studies and personalized treatment.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}