Arthritis Research & Therapy最新文献

{"title":"Exploring the therapeutic effect of human recombinant IL11 on lesioned OA human osteochondral explants","authors":"Margo Tuerlings, Evelyn Houtman, Elisa J.H. Muusers, Janneke Simon, Maurice W. de Haan, Ilja Boone, Yolande F.M. Ramos, Rachid Mahdad, Ingrid Meulenbelt","doi":"10.1186/s13075-025-03480-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03480-4","url":null,"abstract":"To explore IL11 co-expression profiles in our previously reported RNA-sequencing dataset of OA articular cartilage, in interaction with IL6, and to investigate the effects of hrIL11 administration as potential therapeutic strategy for OA articular cartilage using our biomimetic aged human osteochondral explant model of OA. We used RNA-sequencing datasets of macroscopically preserved and lesioned OA articular cartilage (N = 35 patients). Spearman correlations were calculated between IL11 and IL6 expression levels and genes expressed in cartilage (N = 20048 genes). Osteochondral explants were isolated from macroscopically preserved and lesioned areas of the joint and were kept in culture for two weeks, with or without exposure to 200ng/ml hrIL11. We found no overlap in correlating genes between IL11 and IL6, indicating their distinct roles in articular cartilage. Moreover, we identified more genes being correlated to IL11 in the lesioned compared to preserved articular cartilage (N = 203 and 106 genes, respectively). Upon treatment of ex vivo OA articular cartilage with hrIL11, we overall observed unbeneficial effects on chondrocyte phenotype, as illustrated by upregulation of MMP13, EPAS1, RUNX2, and POSTN. We did not observe significant differences in Mankin scores upon addition of hrIL11. The current study showed that treatment of OA articular cartilage with hrIL11 is unlikely to be beneficial despite previous indications of hrIL11 as potential druggable target. These findings underscore the importance of functionally investigating OA risk genes. Better understanding of IL11 signaling and the underlying pathways is necessary towards the development of OA treatment strategy.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"63 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer incidence and the influence of immunosuppressive agents in Korean patients with systemic lupus erythematosus: a retrospective cohort study","authors":"Soo-Kyung Cho, Jung-Yong Han, Yena Jeon, Seung-Hun You, Sun-Young Jung, Eun Jin Jang, Yoon-Kyoung Sung","doi":"10.1186/s13075-025-03482-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03482-2","url":null,"abstract":"To investigate cancer incidence and the potential influence of immunosuppressive agents in Korean systemic lupus erythematosus (SLE) patients. We conducted a retrospective analysis utilizing data from the Korea Healthcare Bigdata Linked Platform, which integrated the National Central Cancer Registry and National Health Insurance Service databases covering the period 2008–2017. Incidence rates (IRs) per 10,000 person-years (PYs) for site-specific cancers of SLE patients were calculated using ICD-O-3 codes. Multivariable logistic regression analysis was utilized to assess the association between immunosuppressive agents and cancer development in SLE patients. A total of 10,013 predominantly female (91%) Korean SLE patients with a mean age of 36.9 ± 15.2 years were included. During a follow-up of 62,268.5 PYs, 368 patients developed cancer. The IRs per 10,000 PYs for total, solid, and hematologic cancers were 59.07, 54.09, and 5.78, respectively. The most prevalent cancers (measured in IRs per 10,000 PYs) were thyroid (17.01, 95% CI 13.78–20.25), breast (8.67, 95% CI 6.36–10.98), stomach (4.49, 95% CI 2.83–6.16), colorectal (4.17, 95% CI 2.57–5.78), and cervical (3.85, 95% CI 2.31–5.39). Approximately half (50.8%) of SLE patients with cancer were diagnosed at the localized Surveillance, Epidemiology, and End Results (SEER) stage. No statistically significant association was found between immunosuppressive agents and cancer development (Odds Ratio 1.03, 95% CI 0.80–1.34). Our study shows that Korean SLE patients using immunosuppressive agents are not significantly more likely to develop cancer. Further research with extended observation is warranted to corroborate these findings.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"33 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suberosin attenuates rheumatoid arthritis by repolarizing macrophages and inhibiting synovitis via the JAK/STAT signaling pathway","authors":"Huan Liu, Qianwei Li, Yuehong Chen, Min Dong, Hongjiang Liu, Jiaqian Zhang, Leiyi Yang, Geng Yin, Qibing Xie","doi":"10.1186/s13075-025-03481-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03481-3","url":null,"abstract":"Rheumatoid arthritis (RA) is a systemic disease that primarily manifests as chronic synovitis of the symmetric small joints. Despite the availability of various targeted drugs for RA, these treatments are limited by adverse reactions, warranting new treatment approaches. Suberosin (SBR), isolated from Plumbago zeylanica—a medicinal plant traditionally used to treat RA in Asia—possesses notable biological activities. This study aimed to investigate the effects and potential underlying pathways of SBR on RA. Tumor necrosis factor-alpha (TNF-α) induced inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS), and the expression of proinflammatory mediators was assessed using q-RT PCR and ELISA after treatment with various SBR concentrations. Bone marrow-derived macrophages (BMDMs) were induced to differentiate into M1 and M2 macrophages, followed by treatment with various SBR concentrations and macrophage polarization assessment. Low-dose (0.5 mg/kg/d) and high-dose (2 mg/kg/d) SBR regimens were administered to a collagen-induced arthritis (CIA) mouse model for 21 days, and the anti-arthritic effects of SBR were evaluated. Network pharmacology and molecular docking analyses were used to predict the anti-arthritic targets of SBR. The effect of SBR on the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was evaluated. SBR suppressed macrophage polarization toward the M1 phenotype while enhancing their polarization toward the M2 phenotype. SBR reduced the levels of proinflammatory mediators in TNF-α-induced RA-FLS. Mechanistically, SBR inhibited the phosphorylation of the JAK1/STAT3 signaling pathway in RA-FLS and M1 macrophages and promoted the phosphorylation of the JAK1/STAT6 pathway in M2 macrophages, enhancing M2 polarization. In vivo, prophylactic treatment of low-dose SBR reduced M1 macrophage infiltration into synovial tissue, increased the proportion of M2 macrophages, and decreased the expression of inflammatory mediators in the serum and synovial tissue, alleviating synovial inflammation. SBR significantly alleviated arthritis in CIA mice through macrophage repolarization and inhibition of inflammation. SBR significantly reduced clinical symptoms, joint pathological damage, and expression inflammatory cytokine expression in CIA mice. SBR exhibited anti-arthritic effects via the JAK1/STAT3 and JAK1/STAT6 signaling pathways, inhibiting synovial tissue inflammation and M1 macrophage polarization while promoting M2 macrophage polarization. Therefore, SBR may be an effective candidate for RA treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do individuals with inflammatory arthritis receive minimally adequate treatment for incident depression and anxiety: A population-based study","authors":"Alyssa Howren, Eric C. Sayre, J. Antonio Avina-Zubieta, Joseph H. Puyat, Deborah Da Costa, Hui Xie, Eileen Davidson, Amit Gupta, Mary A. De Vera","doi":"10.1186/s13075-024-03466-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03466-8","url":null,"abstract":"Describe patterns of pharmacotherapy and psychological treatment and evaluate receipt of minimally adequate treatment for incident depression and anxiety in individuals with inflammatory arthritis (IA). We used population-based linked administrative health databases from British Columbia, Canada to evaluate pharmacotherapy and psychological treatments for incident depression and/or anxiety among individuals with IA and without IA (‘IA-free controls’). We defined minimally adequate pharmacotherapy as antidepressant prescriptions filled with ≥ 84 days’ supply and adequate psychological treatment as ≥ 4 counselling/psychotherapy services. Multivariable logistic regression models were used to evaluate the odds of individuals with IA receiving minimally adequate pharmacotherapy and/or psychological treatment compared to IA-free controls. 6,951 (mean age 54.8 ± 18.3 years; 65.5% female) individuals with IA had incident depression and 3,701 (mean age 52.9 ± 16.8 years; 74.3% female) had incident anxiety. Minimally adequate pharmacotherapy and psychological treatment for depression was respectively observed in 50.5% and 19.6% of those with IA, proportions similar to IA-free controls (pharmacotherapy: aOR 1.10, 95% CI 1.00 to 1.21; psychological: aOR 1.07, 95% CI 0.94 to 1.21). Results were similar regarding anxiety treatment. Individuals with IA had a significantly greater likelihood of dispensing ≥ 1 benzodiazepine (anxiety: IA 45.0%, IA-free controls 39.0%, p-value < 0.001) and ≥ 1 tricyclic antidepressant prescription (anxiety: IA 12.8%, IA-free controls 7.8%, p-value < 0.001). Significantly higher average days’ supply of benzodiazepines was observed for IA (anxiety: IA 123.7 days, controls 112.4 days, p-value = 0.003). A substantial proportion of individuals with IA were not receiving adequate mental health treatment for depression and anxiety, a finding similar for IA-free controls. The undertreatment of mental disorders for people with IA has well-known negative implications for the provision of effective rheumatology care. It remains fundamental to expand publicly funded health care to include mental health services in an effort to address unmet counselling needs.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome miR-199a-5p modulated vascular remodeling and inflammatory infiltration of Takayasu’s arteritis","authors":"Shuning Guo, Jiehan Li, Shurui Pang, Jing Li, Xinping Tian","doi":"10.1186/s13075-025-03475-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03475-1","url":null,"abstract":"Advances in treatment have swiftly alleviated systemic inflammation of Takayasu’s arteritis (TAK), while subclinical vascular inflammation and the ensuing arterial remodeling continue to present unresolved challenges in TAK. The phenotypic switching of vascular smooth muscle cells (VSMC) is regarded as the first step in vascular pathology and contributes to arterial remodeling. Exosomes facilitate the transfer and exchange of proteins and specific nucleic acids, thereby playing a significant role in intercellular communication. Little is known about the modulatory role of serum exosomes in phenotypic switching of VSMC and vascular remodeling in TAK. Serum exosomes isolated from TAK patients were co-cultured with VSMC to identify the modulatory role of exosomes. VSMC were transfected with miR-199a-5p mimic and inhibitor. CCK8 assays and EdU assays were performed to measure proliferative ability. The migration of VSMC was evaluated by scratch assays and transwell migration assays. The flow cytometry was employed to identify apoptosis of VSMC. Dual-luciferase reporter assay, RNA immunoprecipitation assay and fluorescence in situ hybridization were utilized to validate the target gene of miR-199a-5p. The correlational analysis was conducted among exosome miRNA, serum MMP2, TIMP2 and clinical parameters in TAK patients. The coculture of VSMC with serum exosome mediated dedifferentiation of VSMC. Through gain- and loss-of-function approaches, miR-199a-5p over-expression significantly increased expression of VSMC marker genes and inhibited VSMC proliferation and migration, whilst the opposite effect was observed when endogenous miR-199a-5p was knocked down. The overexpression of miR-199a-5p suppressed VSMC apoptosis. Further, MMP2 serves as functional target gene of miR-199a-5p. The correlation analyses revealed an inverse correlation between Vasculitis Damage Index and exosome miR-199a-5p level or serum MMP2, which requires validation in a larger cohort. Our study indicated that the miR-199a-5p/MMP2 pathway played a role in inhibiting the migration, proliferation and apoptosis of VSMC. The decreased secretion of MMP2 may potentially prompt the intimal infiltration of inflammatory cells within the vascular wall, offering a novel therapeutic opportunity by tackling both inflammatory responses and the neointimal overgrowth associated with TAK arterial damage. Moreover, exosome miR-199a-5p and MMP2 derived from serum possess potential as future biomarkers for vascular injury.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"56 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The serum level of sclerostin decreases in radiographic axial spondyloarthritis patients with fatty lesions","authors":"Xuegang Li, Haijian Jiang, Xu Wang, Shuping Zhong","doi":"10.1186/s13075-025-03479-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03479-x","url":null,"abstract":"Currently, the pathophysiology of new bone formation in radiographic axial spondyloarthritis (r-axSpA) remains unclear. Cellular elements and their secreted bone turnover markers might be one of the underlying mechanisms that drive the new bone formation. Our study aimed to investigate the role of bone turnover markers in r-axSpA patients with fatty lesions. 73 r-axSpA patients were enrolled in this study. 48 and 25 patients were divided into r-axSpA group with and without fatty lesions. Clinical variables were collected and all patients received comprehensive rheumatologic assessment for disease activity, including Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Axial Spondyloarthritis Disease Activity Score (ASDAS). Fatty lesions in the sacroiliac joints (SIJs) were scored independently by two radiologists. Serum levels of bone turnover markers, including sclerostin, osteoprotegerin (OPG), procollagen I N-terminal propeptide (PINP), cross linked C-telopeptide of type I collagen (CTX-I), osteocalcin (OC), were measured using enzyme-linked immunosorbent assays. There were no significant differences between two groups in terms of gender, age, body mass index (BMI), duration, smoking, HLA-B27 positivity rate, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), BASDAI, ASDAS-ESR, ASDAS-CRP, biological disease-modifying anti-rheumatic drugs (bDMARDs) rate. No significant differences were observed in terms of OPG, PINP, CTX-I or OC between two groups. The mSASSS were higher in fatty lesions group than in those without fatty lesions (p < 0.001). The serum sclerostin levels were significantly lower in r-axSpA patients with fatty lesions than in those without fatty lesions (p < 0.001). There were correlations between BMI, mSASSS and sclerostin with the comprehensive Berlin scoring method (CBM) scores in the univariate analysis (ρ = 0.311, ρ = 0.306, ρ = -0.920, respectively). However, only sclerostin had correlation with the CBM scores in multivariate analysis (ρ = -0.040, p < 0.001). In the r-axSpA patients with fatty lesions, serum sclerostin levels are declined. Serum sclerostin might be useful as a biomarker to predict the progression of the chronic inflammation in SIJs in r-axSpA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"118 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Anti-PAD4, Anti-CarP, and Anti-RA33 antibodies combined with RF and ACPA in predicting abatacept response in rheumatoid arthritis","authors":"Alberto Floris, Maria Maddalena Angioni, Mattia Fadda, Micaela Rita Naitza, Mattia Congia, Elisabetta Chessa, Matteo Piga, Alberto Cauli","doi":"10.1186/s13075-024-03470-y","DOIUrl":"https://doi.org/10.1186/s13075-024-03470-y","url":null,"abstract":"To explore the role of newly emerging autoantibodies (AAbs) - peptidyl-arginine deiminase 4 (aPAD4), carbamylated proteins (aCarP), and anti-RA33 (aRA33) - alongside the traditionally assessed rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), in predicting the response to abatacept (ABT) and its retention rate in rheumatoid arthritis (RA) patients. Data from 121 consecutive ABT-treated RA patients were recorded. The RF and ACPA status were retrospectively assessed by reviewing the patients’ clinical records. Positivity for aPAD4, aCarP and aRA33 were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The achievement of a moderate or good EULAR response at 6 months and the 3-years retention were analyzed as treatment outcomes. Multiple logistic regression models and Cox regression hazard analysis models were built to identify the association between such outcomes and the different AAbs, after adjustment for different confounders. The AAbs were assessed both individually and in different combinations to identify the most robust predictive model. In the studied cohort, RF, ACPA, aPAD4, aCarP and aRA33-Ab tested positive in 74.4%, 69.4%, 43.8%, 23.9%, 14.9% patients, respectively. A moderate or good EULAR response at 6 months was achieved by 64.5% of subjects and the cumulative 3-years retention rate was 56.6%. A higher EULAR response rate was recorded in patient with positivity for RF (67% in subjects tested positive vs. 58% in negative), ACPA (68% vs. 57%), aPAD4 (68% vs. 62%), and aCarP (72% vs. 62%), although statistical significance was not reached likely due to sample size limitations. Similarly, ACPA, aPAD4, aCarP were associated with higher 3-year retention rates, though not statistically significant individually. The combined analysis revealed that positivity for ACPA and/or aPAD4 predicted a significantly higher EULAR response rate at 6 months compared with double negativity (adjusted OR 2.7, p 0.026). Furthermore, positivity for at least one of ACPA, aPAD4, or aCarP predicted a significantly higher 3-year ABT retention rate compared to triple negativity (62.1% single or double positive vs. 33.5% triple negative, adjusted HR 0.48, p 0.022). This study highlights the potential benefits of using a combined assessment of ACPA aPAD4 and aCarP in predicting effectiveness of ABT in RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"24 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of spinal damage in patients with axial spondyloarthritis as assessed by MRI: a prospective and blinded study","authors":"Andreas Haidmayer, Gabriel Adelsmayr, Christopher Spreizer, Eva Valentina Klocker, Franz Quehenberger, Michael Fuchsjaeger, Jens Thiel, Josef Hermann","doi":"10.1186/s13075-024-03465-9","DOIUrl":"https://doi.org/10.1186/s13075-024-03465-9","url":null,"abstract":"Axial spondyloarthritis (SpA) leads to structural bone lesions in every part of the vertebral column. These lesions are only partially visualized on conventional radiographs, omitting posterior parts of the vertebral column and the thoracic spine, that may nevertheless contribute to impaired spinal mobility and function in patients with axial SpA. In this prospective and blinded investigation, we assessed the distribution of structural spinal lesions using magnetic resonance imaging (MRI) of the whole spine in 55 patients with axial SpA classified according to the Assessment in Spondyloarthritis International Society (ASAS) criteria. After assessment of spinal mobility and function two blinded radiologists independently evaluated MRIs of 23 vertebral units in every patient. Non-parametric statistical methods, Spearman‘s correlation and linear regression models were used to analyze structural lesion distribution and the relationship with clinical spinal mobility and function parameters. In 55 patients with axial SpA (13 females, average disease duration 14.9 years) 657 ventral and 139 dorsal vertebral body structural bone lesions and, notably, 534 facet joint lesions could be visualized. The median number of lesions per patient was higher in the thoracic (8.5, range 1.0–41.0) than in the lumbar (7.5, range 0.0-27.5) and the cervical spine (3.5, range 0.0-24.5). A negative correlation was noted between the number of osteoproliferative structural bone lesions and impairment of spinal mobility and function in univariate, but not in multivariate analyses. MRI of the whole spine revealed a high prevalence of lesions in dorsal parts of the vertebral column and in the thoracic spine in patients with axial SpA that may not be adequately visualized on conventional radiographs. These findings could further contribute to a better understanding of reduced mobility of the spine typically associated with axial SpA and assist diagnostics.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eltrombopag for the treatment of refractory connective tissue disease-related thrombocytopenia: a pilot study of 52 cases","authors":"Siying Deng, Bei Wang, Ziwei Hu, Shaozhe Cai, Lingli Dong","doi":"10.1186/s13075-024-03472-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03472-w","url":null,"abstract":"The objective of this study was to investigate the therapeutic effectiveness and safety profile of Eltrombopag, a thrombopoietin receptor agonist, as prolonged therapy in refractory CTD-ITP patients. We conducted a pilot observational study of Eltrombopag in CTD-ITP patients who were unresponsive to or intolerant of conventional medications. Eltrombopag was administered orally at 25–75 mg/qd and adjusted on the basis of tolerance and efficacy until a minimum dosage of 25 mg/qd was reached. Clinical and laboratory data were collected and analysed monthly. The therapeutic response, relapse, and adverse events during the follow-up were also reviewed and evaluated. Fifty-two patients were enrolled and followed monthly for a median of 6 months. Thirty-six (90%) patients achieved durable overall remission. The remission rates were 67.5% at month 1, 87.5% at month 2, 97.5% at month 3, and 95% at month 6. The platelet count of the patients improved significantly, with the median reaching 50 × 109/L within 2 weeks (p = 0.003). Disease activity indices were reduced in SLE and pSS patients (p = 0.016), allowing glucocorticoid tapering (p = 0.004). One patient had no response, four relapsed, and fifteen (28.8%) experienced clinically relevant adverse events. In the analyses, protopathy, comorbidity, and prior treatment were associated with efficacy. For refractory CTD-ITP patients, Eltrombopag demonstrated significant clinical improvement, safety, and a steroid-sparing effect with prolonged use. Patient characteristics at baseline may affect treatment efficacy. First-line treatment with immunosuppressant therapy has a poor effect on ITP secondary to connective tissue disease and brings unignorable side effects on patients. Few studies have sufficiently elucidated the effects of Eltrombopag, a thrombopoietin receptor agonist, in refractory ITP secondary to CTD. Here, we report a series of refractory ITP-CTD patients treated with Eltrombopag. A 90% durable overall remission rate was observed at week 24, and remission rates promptly increased from 67.5% at month 1 to 89.5% at month 2. Eltrombopag had a rapid onset of action and permitted a steroid-sparing effect as the response was sustained. A 28.8% adverse event rate was observed. The baseline characteristics of patients may influence drug efficacy. This study may provide important supporting information for developing a treatment strategy for refractory CTD-ITP patients based on Eltrombopag.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"204 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of macrophage polarization and pyroptosis in collagen-induced arthritis through MSC-exo and ginsenoside Rh2","authors":"Zhongsheng Zhou, Shuhui Wu, Yang Li, Pu Shao, Jinlan Jiang","doi":"10.1186/s13075-025-03473-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03473-3","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, tissue damage, and fibrosis, significantly affecting the quality of life. While there are currently some effective treatments available, they often come with side effects. There is an urgent need to find new treatments that can further improve therapeutic outcomes and reduce side effects. Our study investigates the role of Mesenchymal Stem Cell exosomes (MSC-exo) combined with Ginsenoside Rh2 (Rh2) in the treatment of RA. We specifically focus on how this combined strategy influences macrophage polarization and pyroptosis. This research utilized a collagen-induced rat arthritis model. The study findings reveal that the combination of MSC-exo combined with Rh2 can inhibit the polarization of M1 macrophages, increase the proportion of M2-like macrophages, and suppress M1-like macrophage pyroptosis via the NLRP3/Caspase11/GSDMD-N pathway. In the rat arthritis model, the combination of MSC-exo and Rh2 showed synergistic therapeutic effects. This research contributes to a deeper understanding of RA’s pathogenesis and presents new potential targeted therapeutic interventions. The combined application of MSC-exo and Rh2 offers promising insights for future innovative strategies in RA treatment, paving the way for more effective management of this autoimmune disease.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"101 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}