Arthritis Research & Therapy最新文献

{"title":"Correction: Real-world sex differences in treatment persistence and reasons for discontinuation in psoriatic arthritis patients: results from the German RABBIT-SpA register.","authors":"Lisa Lindner, Anja Weiß, Andreas Reich, Christine Baumann, Frank Behrens, Xenofon Baraliakos, Anne C Regierer","doi":"10.1186/s13075-026-03820-y","DOIUrl":"10.1186/s13075-026-03820-y","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13191841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986259","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":"Elevated sST2 associates with cardiac involvement and declines after treatment in newly diagnosed patients with idiopathic inflammatory myopathies.","authors":"Balsam Hanna, Ingrid E Lundberg, Anna-Karin H Ekwall, Daniel Glinatsi, Egidija Sakiniene, Zhicheng Hu, Rille Pullerits, Tao Jin","doi":"10.1186/s13075-026-03830-w","DOIUrl":"10.1186/s13075-026-03830-w","url":null,"abstract":"<p><strong>Objective: </strong>Cardiac involvement (CI) is a major determinant of poor prognosis in idiopathic inflammatory myopathies (IIM). Soluble suppression of tumorigenicity 2 (sST2) is a biomarker linked to cardiac inflammation and remodelling, but its role has scarcely been explored in IIM. We aimed to investigate the levels of sST2 and its longitudinal profile in patients with IIM and CI.</p><p><strong>Methods: </strong>Serum sST2 levels were measured longitudinally over the course of two years in 34 patients with newly diagnosed IIM and in 109 patients with established IIM from a cross-sectional cohort, as well as in age and gender matched healthy controls (HC) and in patients with rheumatoid arthritis (RA). CI was assessed using cardiac magnetic resonance (CMR) in newly diagnosed IIM patients. Associations between sST2 and clinical parameters were analyzed.</p><p><strong>Results: </strong>Patients with newly diagnosed IIM exhibited significantly higher sST2 levels at diagnosis compared to HC (P < 0.0001) and patients with established IIM (P < 0.0001). sST2 levels were highest at diagnosis, decreased significantly by 6 months, and remained lower during follow-up. sST2 levels were positively associated with cardiac troponin I and N-terminal pro-brain natriuretic peptide (P = 0.0001 and P = 0.0001, respectively). Importantly, IIM patients with active CMR-verified CI exhibited significantly higher sST2 levels than those without ongoing CI. In contrast, patients with established IIM had sST2 levels comparable to HC and RA patients.</p><p><strong>Conclusion: </strong>sST2 is elevated in early IIM and closely associated with cardiac biomarkers and CMR-verified cardiac inflammation. Its dynamic decline with treatment suggests potential utility as a biomarker for early detection and monitoring of CI in IIM.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970024","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":"Lipid metabolism dysregulation in rheumatoid arthritis: from multi-omics discovery to adjunctive therapy with conjugated linoleic acid.","authors":"Jianghua Chen, Zhuming Yin, Wantai Dang, Congcong Jian, Tingting Wang, Jiaxin Huang, Xiaoting Zhu, Yuanli Wei, Jing Gao, Jie Zhang, Jiang Su, Jing Zhu, Jianhong Wu, Qinghua Zou, Pilei Si, Fanxin Zeng","doi":"10.1186/s13075-026-03831-9","DOIUrl":"10.1186/s13075-026-03831-9","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to comprehensively analyze the role of metabolic signatures in rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>A total of 599 samples, including fecal (n = 206), plasma (n = 206), and peripheral blood mononuclear cell (PBMC) samples (n = 187), were collected from 443 individuals with RA, systemic lupus erythematosus, and controls. Fecal, plasma and PBMC samples were subjected to 16S rRNA sequencing, liquid chromatography-tandem mass spectrometry, RNA sequencing and 4D DIA proteomics, respectively. A collagen-induced arthritis mouse model was used to investigate the role of the metabolite conjugated linoleic acid (CLA) in experimental arthritis. An RA clinical cohort (n = 26) was recruited to validate the potential role of CLA as an adjunct to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) therapy.</p><p><strong>Results: </strong>Multi-omics analysis revealed comprehensive alterations in metabolic signatures (metabolism-related molecules, metabolites, and metabolic pathways) in RA. Lipid metabolism pathways, particularly linoleic acid metabolism, appear to play a significant regulatory role in RA progression. Metabolites and molecules involved in linoleic acid metabolism were significantly associated with clinical phenotypes in RA patients. In animal experiments, CLA reduced arthritis scores, swollen joint counts, histopathological scores, and inflammatory levels. Finally, CLA supplementation accelerated the reduction of inflammatory levels in RA patients receiving csDMARDs therapy.</p><p><strong>Conclusion: </strong>These findings reveal lipid metabolism as a druggable axis, position dietary CLA as an adjunct to improve outcomes in RA, and offer a new avenue to enhance remission rates.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970008","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":"Targeting mitochondrial fission-autophagy axis in rheumatoid arthritis: leflunomide promote apoptosis of fibroblast-like synoviocytes.","authors":"Xiaoxue Wang, Jianling Su, Shiqi Feng, Jiaqi Qu, Wei Jiang, Jiping Chen, Xuemei Fan, Yongmei Yu, Jiayi Luo, Yang Li","doi":"10.1186/s13075-026-03828-4","DOIUrl":"10.1186/s13075-026-03828-4","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and joint destruction, driven by aberrantly activated fibroblast-like synoviocytes (RA-FLS). Mitochondrial dysfunction, particularly excessive mitochondrial fission, contributes to RA-FLS activation and apoptosis resistance, yet the impact of disease-modifying antirheumatic drugs (DMARDs) on mitochondrial dynamics remains unclear. Here, we examined the correlation between mitochondrial dynamics proteins and RA disease activity and investigated the effects of leflunomide and methotrexate (MTX) on mitochondrial dynamics, autophagy, and apoptosis in RA-FLS and collagen-induced arthritis (CIA) mice. Mitochondrial dynamics proteins in synovial fluid correlated more strongly with disease activity than those in peripheral blood, and were partially normalized in RA patients receiving leflunomide or MTX. Both leflunomide and MTX attenuated TNF-induced mitochondrial fragmentation and decreased mitochondrial membrane potential in RA-FLS. Notably, leflunomide, but not MTX inhibited DRP1 phosphorylation at Ser616, increased reactive oxygen species, and induced apoptosis via the BCL-2/BAX/caspase-3 pathway. Additionally, leflunomide influenced autophagy by promoting LC3B II/I and enhancing p62 expression. In CIA mice, leflunomide reduced the expression and phosphorylation of DRP1 on synovium, increased the expression of OPA1, and alleviated joint inflammation and destruction. These findings identify mitochondrial dynamics as a therapeutic target in RA and suggest that leflunomide promotes apoptosis of RA-FLS by modulating the mitochondrial fission-autophagy axis.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959431","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":"Aberrant sphingosine-1-phosphate receptor 1 expression on activated naive B cells associated with disease activity and lupus nephritis in systemic lupus erythematosus.","authors":"Pachara Tianpothong, Piyawan Kochayoo, Thanitta Suangtamai, Sasicha Suksapan, Pongsakorn Thawornpan, Chaniya Leepiyasakulchai, Pintip Ngamjanyaporn, Prapaporn Pisitkun, Patchanee Chootong","doi":"10.1186/s13075-026-03829-3","DOIUrl":"10.1186/s13075-026-03829-3","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is characterized by the immune system producing autoantibodies that target the body's own cells and tissues, leading to inflammation and tissue damage. Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in regulating immune cell trafficking, and its function relies on a gradient of sphingosine-1-phosphate (S1P). During inflammatory immune responses, the S1P gradient is altered, promoting lymphocyte migration to inflammatory sites. Consequently, S1PR1 has become a therapeutic target for inhibiting lymphocyte egress from lymphoid tissues in autoimmune and inflammatory diseases. However, knowledge of S1PR1 expression and function in B cell subsets and antibody-secreting cells (ASCs) in SLE remains limited.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells (PBMCs) from forty-nine patients with SLE were enrolled to assess S1PR1 expression in B cell subsets and plasma cells. Significant differences in surface S1PR1 expression on activated naive (aNAV), Double Negative 2 (DN2) B cells and ASCs were further analyzed for correlations with disease activity, Lupus Nephritis (LN) involvement, inflammatory markers, S1P levels, and chemokine receptor expression.</p><p><strong>Results: </strong>Intracellular S1PR1 expression was significantly increased across all B cell subsets, including naive (rNAV and aNAV), memory (SWM, USM, DN1, DN2), and ASCs. In contrast, surface S1PR1 expression differed markedly among subsets, with downregulation observed in aNAV and DN2 B cells and upregulation in ASCs. Further analysis revealed that surface S1PR1 downregulation on aNAV B cells was significantly associated with active disease status, SLEDAI-2 K scores, and LN involvement. Inflammatory markers (IL-6, IL-8, and C3c levels) showed no correlation with surface S1PR1 expression, whereas erythrocyte sedimentation rate (ESR) demonstrated a significant negative correlation. In addition, lupus aNAV and DN2 B cells exhibited reduced surface CXCR3 expression without correlation to S1PR1 expression, whereas other B cell subsets in SLE subjects showed a significant correlation between CXCR3 and S1PR1 expression.</p><p><strong>Conclusion: </strong>Surface S1PR1 expression was downregulated in aNAV and DN2 B cells. Clinically, decreased surface S1PR1 expression on aNAV B cells was significantly correlated with active status, increased disease activity, LN involvement, and elevated ESR. The increased S1P levels, along with S1PR1 and CXCR3 downregulation, suggest that chronic activation characteristic of SLE may drive S1PR1 desensitization or internalization in aNAV B cells, thereby altering their ability to dynamically recirculate or respond to inflammation-associated signal target tissues.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940016","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":"Clinical characteristics and response to standard-of-care treatment in systemic lupus erythematosus patients with or without anti-ribonucleoprotein (RNP) antibodies: an Australian, multi-centre cohort study.","authors":"Rangi Kandane-Rathnayake, Rachel Koelmeyer, Shereen Oon, Maureen Rischmueller, Yumi Oh, Sean O'Neill, Geraldine Hassett, Sachin Khetan, Ted Tsai, Fiona Goldblatt, Ashleigh Hennessey, Dwarakanathan Ranganathan, Adrienne Lefeber, Tamas Shisha, Peter Gergely, Mandana Nikpour, Eric Morand, Alberta Hoi","doi":"10.1186/s13075-026-03823-9","DOIUrl":"10.1186/s13075-026-03823-9","url":null,"abstract":"<p><strong>Background: </strong>Anti-ribonucleoprotein (RNP) (auto)antibodies are frequently detected in patients with systemic lupus erythematosus (SLE) although their associations with SLE disease activity remain incompletely understood. We compared patient characteristics, including disease severity outcomes, between adult patients with SLE with or without anti-RNP antibodies (RNP + versus RNP-).</p><p><strong>Methods: </strong>We used data from a national, multicentre registry of SLE patients in Australia, collected prospectively between 2007 and 2023. Anti-RNP status and other serological profiles along with demographics were recorded at enrolment. At each routine clinic visit, medication details and disease activity indicators (SLEDAI-2 K, PGA) were captured, and treat-to-target (T2T) states, lupus low disease activity state (LLDAS) and DORIS remission (REM), were determined. Clinical characteristics were compared between RNP + and RNP- patients at 6 months (182 ± 30 days) and 12 months (365 ± 30 days) from enrolment.</p><p><strong>Results: </strong>A total of 587 patients were studied. 174 (29.6% (95%CI: 26.1%, 33.4%)) were RNP + with significantly higher disease activity and more medication use at enrolment compared with RNP- patients (SLEDAI-2 K median [IQR]: 8.0 [4.0, 10.0] versus 4.0 [2.0, 8.0], p < 0.001; PGA: 0.9 [0.4, 1.2] versus 0.5 [0.2, 1.0], p < 0.001; daily glucocorticoid dose 6.8 [0.0, 15.0] versus 3.0 [0.0, 10.0] mg/day, p < 0.001). RNP + group had more patients with renal, cutaneous, and serological activity. At enrolment, a greater proportion of RNP + patients had active disease (SLEDAI-2 K ≥ 6) compared with RNP- patients (53% versus 41%, p < 0.007), whereas significantly fewer RNP + patients were in LLDAS (20% versus 32.2%, p-value = 0.004) or REM (11.6% versus 22.6%, p-value = 0.006). RNP + patients were 18-fold more likely to be positive for anti-Sm antibodies, and associations with disease activity attenuated upon adjustment for this, though highest disease activity was observed in patients positive to both anti-RNP and anti-Sm autoantibodies (RNP + Sm +). Disease activity indicators between RNP + and RNP- groups converged within the first 12 months following enrolment. Glucocorticoid and immunosuppressant use remained significantly higher in RNP + Sm + patients.</p><p><strong>Conclusions: </strong>Anti-RNP positive patients presented with a higher burden of disease activity, and required more intensive treatment with glucocorticoids and immunosuppressants during the first year since study of follow-up, but this was largely driven by the strong association of anti-RNP positivity with anti-Sm positivity.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873139","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":"IRE1/p‑JNK/NRF2 axis-mediated GPX4 upregulation underlies ferroptosis resistance in rheumatoid arthritis fibroblast-like synoviocytes.","authors":"Jiaxi Liu, Wenhui Xie, Yongping Cao, Liang Zhang, Yan Geng, Zhuoli Zhang","doi":"10.1186/s13075-026-03827-5","DOIUrl":"10.1186/s13075-026-03827-5","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis fibroblast‑like synoviocytes (RA‑FLS) exhibit chronic endoplasmic reticulum stress with activation of the IRE1/phospho‑JNK arm of the unfolded protein response; yet, they remain resistant to apoptosis. Although ferroptosis has been implicated in the pathogenesis of rheumatoid arthritis, the mechanisms underlying ferroptosis resistance in RA‑FLS remain poorly understood.</p><p><strong>Methods: </strong>A total of 17 patients who underwent joint replacement were included (RA n = 9; OA n = 8). Primary fibroblast-like synoviocytes (FLS; ≥3 donors per assay) were analyzed by RT-qPCR and western blotting for IRE1, p-JNK, NRF2 and GPX4. Signaling was modulated with siRNA or inhibitors against ERN1 or NRF2. Ferroptosis was assessed by transmission electron microscopy, lipid peroxidation, Fe²⁺ and glutathione depletion; cell phenotypes were evaluated by invasion, wound-healing and CCK-8 assays. In vivo (≥ 4 per group), a collagen-induced arthritis (CIA) rat model received the IRE1 inhibitor 4µ8c; micro-CT, joint pathology and biochemical markers were evaluated.</p><p><strong>Results: </strong>RA-FLS showed elevated IRE1/p-JNK, increased total and nuclear NRF2, and higher GPX4 versus OA-FLS, and were more resistant to ferroptosis. ERN1 knockdown reduced p-JNK, NRF2 and GPX4 and increased lipid peroxidation, iron accumulation, glutathione loss and ferroptosis. NRF2 inhibition also sensitized RA-FLS to ferroptosis and attenuated aggressive phenotypes. In CIA rats, IRE1 inhibition partially attenuated bone destruction, lowered serum IL-1β/MMP9, and reduced synovial GPX4.</p><p><strong>Conclusion: </strong>Sustained IRE1/p-JNK/NRF2 signaling upregulates GPX4, linking ER stress to ferroptosis resistance in RA-FLS. Targeting IRE1 lowers GPX4 and restores ferroptotic sensitivity, suggesting a potential therapeutic strategy for RA.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863474","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":"Aurora A kinase activation contributes to the fibrotic phenotype in systemic sclerosis through primary cilia shortening.","authors":"Rebecca Wells, Begoña Caballero-Ruiz, Panji Mulipa, Alex J Timmis, Maria E Teves, John Varga, Francesco Del Galdo, Rebecca L Ross, Natalia A Riobo-Del Galdo","doi":"10.1186/s13075-026-03826-6","DOIUrl":"10.1186/s13075-026-03826-6","url":null,"abstract":"<p><strong>Background: </strong>Systemic sclerosis (SSc) is a severe autoimmune disease characterised by progressive fibrosis driven by fibroblast activation. Primary cilia, key hubs for profibrotic signalling, are markedly shortened in SSc fibroblasts, but the mechanisms underlying this phenotype remain unclear. This study aimed to define the signalling pathways responsible for primary cilia shortening and fibroblast activation in SSc.</p><p><strong>Methods: </strong>Primary dermal fibroblasts from SSc patients and healthy controls were analysed for cilia incidence and length by immunofluorescence, profibrotic marker expression by qPCR, and contractility using gel contraction assays. Cells were treated with TGFβ1 and pharmacological inhibitors targeting AURKA, HDAC6, ROCK2, and Smad3 signalling. CAV1-silenced fibroblasts were used as an in vitro model of SSc.</p><p><strong>Results: </strong>Maintenance of the constitutively short primary cilia phenotype in SSc fibroblasts did not require active TGFβ signalling. However, TGFβ1 induced reversible cilia shortening in healthy fibroblasts and further shortened cilia in SSc fibroblasts to a similar final length, mediated by Rho/ROCK2 rather than canonical Smad3-dependent signalling. Constitutive cilia shortening in SSc was driven by aberrant AURKA activity upstream of HDAC6, promoting ciliary disassembly. Pharmacological inhibition of AURKA or HDAC6 selectively elongated cilia in SSc fibroblasts, reduced profibrotic marker expression, and abrogated fibroblast contractility, but it did not affect healthy control cells. CAV1-silenced fibroblasts similarly exhibited constitutive cilia shortening that was reversed by AURKA inhibition without affecting healthy cells.</p><p><strong>Conclusions: </strong>The AURKA/HDAC6 axis maintains short primary cilia and promotes fibroblast activation in SSc. These findings reveal a mechanistic link between cilia morphology and fibrosis and identify AURKA as a potential therapeutic target for SSc-associated tissue remodelling.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833075","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":"Therapeutic subtypes of knee osteoarthritis: differential treatment effects among predicted endotypes in past clinical trials.","authors":"Monica T Hannani, Peder Frederiksen, Morten A Karsdal, Cecilie L Bager, Asger R Bihlet, Karin Tunblad, Fredrik Öberg, Jamie E Collins, Virginia B Kraus, David J Hunter, Jaume Bacardit, Anne-Christine Bay-Jensen, Christian S Thudium","doi":"10.1186/s13075-026-03825-7","DOIUrl":"10.1186/s13075-026-03825-7","url":null,"abstract":"<p><strong>Background: </strong>Molecular endotyping may facilitate the successful development of personalized treatments of knee osteoarthritis (KOA). The aim of this exploratory and hypothesis-generating study was to develop a clinically actionable tool for predicting molecular endotypes of KOA using blood-based biomarkers, and to explore the potential for differential treatment effects across biomarker-based endotypes in prior phase II-III KOA drug trials.</p><p><strong>Methods: </strong>Fourteen biomarkers from 226 KOA participants from IMI-APPROACH were assessed for a multinomial logistic regression model to predict structural damage, inflammation, and low tissue turnover endotypes. An optimized panel of six serum biomarkers (C2M, C3M, N-MID, PRO-C2, PRO-C4, sCTX-I) was identified quantitatively by testing all biomarker combinations in models adjusting for age, sex, and BMI. These biomarkers were used for endotype predictions in KOA participants from the randomized placebo-controlled trials MIV-711 (n = 244) (NCT02705625), salmon calcitonin (n = 947) (NCT00486434), and UBX0101 (n = 175) (NCT04129944).</p><p><strong>Results: </strong>The structural damage endotype showed the greatest numerical 26-week reduction in NRS knee pain when treated with MIV-711 (-6.46%; 95% CI: -16.23%, 3.31%). Notably, only the structural damage endotype had a significant two-year reduction in WOMAC pain when treated with salmon calcitonin (-6.19%; 95% CI: -10.55%, -1.83%). Considering the subset treated with salmon calcitonin with the top 20% highest probability of belonging to the structural damage endotype, a 9-15% reduction in standard deviation of the two-year change in WOMAC pain was observed. Enriching the trial for this subset with lower outcome variability could have led to an 18-28% reduction in the needed sample size.</p><p><strong>Conclusions: </strong>This exploratory study suggests the feasibility of predicting KOA endotypes using a minimal panel of tissue-turnover biomarkers. The observed treatment effects of anti-bone resorptive treatments and reduced outcome variability in the structural damage endotype may subtly indicate that aligning treatments with endotypes and drug modes of action can possibly enhance their therapeutic efficacy. Further investigation is needed to establish the true clinical utility of biomarker-based endotyping. Endotype-informed trial design and recruitment may represent a promising strategy to increase the likelihood of success in future KOA clinical trials.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832449","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":"Peripheral blood transcriptomic analysis of patients with rheumatoid arthritis associated interstitial lung disease reveals: distinct molecular signature with evidence of humoral and myeloid immunity.","authors":"Sofia Flouda, Maria Grigoriou, George Sentis, Alexandros Grivas, Nikos Malissovas, Aggelos Banos, Konstantinos Thomas, Noemin Kapsala, Anastasia Filia, Dionysis Nikolopoulos, Theofanis Karageorgas, Vasilios Tzilas, Antonis Fanouriakis, Dimitrios T Boumpas","doi":"10.1186/s13075-026-03767-0","DOIUrl":"10.1186/s13075-026-03767-0","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in rheumatoid arthritis (RA). RNA sequencing (RNA-seq) of peripheral blood may provide an unbiased look at pathogenetic events involved.</p><p><strong>Methods: </strong>Peripheral blood was collected from RA-ILD (n = 11), RA non-ILD (n = 10), psoriatic arthritis (PsA, n = 23)patients and healthy controls (HC, n = 7) for transcriptomic analysis. All patients in the RA-ILD group were under treatment during sampling, GC and cDMARDs. The gene expression profile of RA ILD was inferred through differential gene expression analysis followed by pathway and enrichment analysis. Further transcriptomic analysis was conducted based on radiological pattern, clinical progression through Modified Medical Research Council (mMRC) Dyspnea scale, and radiological progression. Drug repurposing analysis was performed to identify perturbagens that counteract RA-ILD-specific signatures. To identify shared pathways between SSc and RA we used publicly available RNA-seq data of patients with systemic sclerosis-associated ILD (SSc-ILD).</p><p><strong>Results: </strong>In RA-ILD patients, differential expression analysis revealed enrichment in immune response pathways, metabolism, IFNα and IFNγ response. Within the RA-ILD subgroup, differential expression analysis of clinical and/or radiological progressors versus non-progressors revealed enriched pathways related to cell cycle, DNA replication, IFNγ response, inflammasome assembly and negative regulation of immune response in progressors. Drug repurposing analysis revealed that ITK, Syk and FAK inhibitors are candidate compounds that potentially reverse the transcriptomic signature of RA-ILD progression. Comparison of RA-ILD and SSc revealed shared pathways related to metabolism, extracellular matrix, IFNγ response and response to microorganisms.</p><p><strong>Conclusions: </strong>In this preliminary study, RA-ILD patients exhibit enhanced immune responses, metabolism and cytokine activation. These data need to be further validated in larger studies.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831813","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}