Arthritis Research & Therapy最新文献

{"title":"Bulk RNA-seq conjoined with ScRNA-seq analysis reveals the molecular characteristics of nucleus pulposus cell ferroptosis in rat aging intervertebral discs","authors":"Shipeng Chen, Jiawei Fu, Jiang Long, Chang Liu, Xuezheng Ai, Dan Long, Xue Leng, Yang Zhang, Zhengao Liao, Changqing Li, Yue Zhou, Shiwu Dong, Bo Huang, Chencheng Feng","doi":"10.1186/s13075-025-03550-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03550-7","url":null,"abstract":"Recently, several studies have reported that nucleus pulposus (NP) cell ferroptosis plays a key role in IDD. However, the characteristics and molecular mechanisms of cell subsets involved remain unclear. We aimed to define the key factors driving ferroptosis, and the characteristics of ferroptotic NP cells subsets during IDD. The accumulation of iron ions in NP tissues of rats caudal intervertebral discs (IVDs) was determined by Prussian blue staining. Fluorescent probe Undecanoyl Boron Dipyrromethene (C11-BODIPY) and lipid peroxidation product 4-Hydroxynonenal (4-HNE) staining were performed to assess lipid peroxidation level of NP cells. The differentially expressed genes in NP tissues with aging were overlapped with FerrDB database to screen ferroptosis driving genes associated with aging-related IDD. In addition, single cell sequencing (ScRNA-seq) was used to map the NP cells, and further identify ferroptotic NP cell subsets, as well as their crucial drivers. Finally, cluster analysis was performed to identify the marker genes of ferroptotic NP cells. Histological staining showed that, compared with 10 months old (10M-old) group, the accumulation of iron ions increased in NP tissues of 20 months old (20M-old) rats, and the level of lipid peroxidation was also enhanced. 15 ferroptosis driving factors related to IDD were selected by cross-enrichment. ScRNA-seq identified 14 subsets in NP tissue cells, among which the number and ratio of 5 subsets was reduced, and the intracellular ferroptosis related signaling pathways were significantly enriched, accompanied by enhanced cell lipid peroxidation. Notably, ranking the up-regulation fold of ferroptosis related genes, we found Atf3 was always present within TOP2 of these five cell subsets, suggests it is the key driving factor in NP cell ferroptosis. Finally, cluster cross-enrichment and fluorescence colocalization analysis revealed that Rps6 +/Cxcl1- was a common molecular feature among the 5 ferroptotic NP cell subsets. This study reveals that ATF3 is a key driver of NP cell ferroptosis during IDD, and Rps6 +/Cxcl1- is a common molecular feature of ferroptotic NP cell subsets. These findings provide evidence and theoretical support for subsequent targeted intervention of NP cell ferroptosis, as well as provide directions for preventing and delaying IDD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"6 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841372","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":"Identifying two pathways to poor prognosis in patients with anti-MDA5 antibodies: insights from prognostic factor and cytokines analysis","authors":"Aya Shimizu, Kazuhiro Kurasawa, Tomoka Hiyama, Sara Komatsu, Azusa Kikuchi, Yuhi Yoshida, Anna Hasegawa, Tomoyuki Miyao, Ayae Tanaka, Satoko Arai, Reika Maezawa, Masafumi Arima, Kei Ikeda","doi":"10.1186/s13075-025-03558-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03558-z","url":null,"abstract":"To identify pathways linking cytokine abnormalities to mortality via prognostic factors in patients with anti-melanoma differentiation-associated protein 5 antibodies (anti-MDA5 Ab). This study included patients with anti-MDA5 Ab whose serum was available. Serum cytokine levels were measured using a multiplex bead assay. Prognostic factors were identified using Cox regression and log-rank test. Prognostic factor groups were identified using principal component analysis (PCA) and factor and cluster analyses. The association between cytokine levels and prognostic factors (groups) was examined using PCA and correlation and path analyses. A prognosis-prediction model was developed using prognostic factors from the different groups. Thirty-five patients were included in this study, of whom 31 had rapidly progressive interstitial lung disease (RP-ILD), and 14 died. We identified white blood cell (WBC), gamma-glutamyl transpeptidase (γ-GTP), lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, and ILD-related factors (Krebs von den Lungen-6 [KL-6], surfactant protein D [SP-D], and CT score) as prognostic factors, in addition to von Willebrand factor and thrombomodulin. Two prognostic factor groups were found: Group 1 included WBC, CRP, and ILD-related factors, and Group 2 included ferritin, LDH, and γ-GTP. Both groups contributed to mortality. Group 1 was associated with IL-6, and Group 2 was related to IL-6, IL-10, and IP-10, and indirectly with TNF-α. A model using CRP (Group1) and γ-GTP (Group2) achieved an area under the curve of 0.84, which was not inferior to previously reported models. Two pathways leading to poor prognosis were identified in anti-MDA5-Ab-positive patients, each marked by specific cytokine abnormalities.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"114 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837077","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":"Impact of Mediterranean diet on mortality in vertebral compression fracture patients","authors":"Longyu Zhang, Yi Zhao, Jiao Xu, Shi Yin, Qiang Wang, Zhiwei Jia, Jingpei Ren, Cong Zhao, Xiaohong Mu","doi":"10.1186/s13075-025-03529-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03529-4","url":null,"abstract":"Vertebral compression fractures (VCF) is a common fragility fracture with high mortality worldwide. The management and prevention of VCF start with a proper nutrition. The Mediterranean diet (MD) is rich in balanced nutrients and has been shown to be beneficial for several chronic diseases. However, the association of adherence to Mediterranean diet (aMED) and prognosis of VCF patients remains unclear. To explore the association between aMED and all-cause and cardiovascular disease (CVD)-cause morality in VCF patients. In present study, patients aged ≥ 40 years old and with the VCF patients measurement were extracted from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. The bone mineral density (BMD) dual-energy X-ray absorptiometry (DXA) was used to diagnose VCF. We used the weighted univariable Cox proportional hazards model to screen the covariates related to the prognosis of VCF patients. We utilized the weighted multivariable Cox proportional hazards models to explore the association between aMED and the risk of mortality in VCF patients, and were described as hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on different complications were further assessed the association. A total of 2,730 eligible VCF patients were included. Until 12 December 2019, 218 (7.99%) deaths were documented. After adjusting for all VCFs, we found a high risk of all-cause mortality (HR = 1.75, 95%CI: 1.13–2.73, P = 0.041) and CVD-cause mortality (HR = 2.35, 95%CI: 1.12–4.91, P = 0.038); however, we found no significant association between aMED and all-cause mortality or CVD-cause mortality (all P > 0.05). Compared to patients without VCF and with aMED score ≥ 6, patients with VCF and aMED score < 6 has a higher risk of all-cause (HR = 2.27, 95%CI: 1.25–4.13, P = 0.025) and CVD-cause mortality (HR = 4.25, 95%CI: 1.64–11.06, P = 0.013). Our study also suggested that compared to patients with aMED ≥ 6, those patients with aMED < 6 has high all-cause (HR = 2.26, 95%CI: 1.22–4.17, P = 0.002) and CVD-cause mortality (HR = 3.31, 95%CI: 1.28–8.57, P = 0.018), this results suggested that aMED may have a moderating effect on the association of VCF and mortality. Subgroups analysis shown this moderating effect remain robust, especially in patients with dyslipidemia (HR: 2.49, 95%CI: 1.29–4.80, P = 0.009), CVD (HR: 3.48, 95%CI: 1.56–7.74, P < 0.001) and CKD (HR: 3.64, 95%CI: 1.50–8.78, P < 0.001). We found aMED have a moderating effect on the association between VCF patients and mortality. Our research further supports the importance of the MD as a potentially healthy eating pattern.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"2 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837108","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":"Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis","authors":"Ilayda Gunes, Elana J. Bernstein, Shawn E. Cowper, Gauri Panse, Niki Pradhan, Lucy Duran Camacho, Nicolas Page, Elizabeth Bundschuh, Alyssa Williams, Mary Carns, Kathleen Aren, Sarah Fantus, Elizabeth R. Volkmann, Heather Bukiri, Chase Correia, Vijaya B. Kolachalama, F. Perry Wilson, Seamus Mawe, J. Matthew Mahoney, Monique Hinchcliff","doi":"10.1186/s13075-025-03508-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03508-9","url":null,"abstract":"The modified Rodnan skin score (mRSS), a measure of systemic sclerosis (SSc) skin thickness, is agnostic to inflammation and vasculopathy. Previously, we demonstrated the potential of neural network-based digital pathology applied to SSc skin biopsies as a quantitative outcome. Here, we leverage deep learning and histologic analyses of clinical trial biopsies to decipher SSc skin features ‘seen’ by artificial intelligence (AI). Adults with diffuse cutaneous SSc ≤ 6 years were enrolled in an open-label trial of belumosudil [a Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitor]. Participants underwent serial mRSS and arm biopsies at week (W) 0, 24 and 52. Two blinded dermatopathologists scored stained sections (e.g., Masson’s trichrome, hematoxylin and eosin, CD3, α-smooth muscle actin) for 16 published SSc dermal pathological parameters. We applied our deep learning model to generate QIF signatures/biopsy and obtain ‘Fibrosis Scores’. Associations between Fibrosis Score and mRSS (Spearman correlation), and between Fibrosis Score and mRSS versus histologic parameters [odds ratios (OR)], were determined. Only ten patients were enrolled due to early study termination, and of those, five had available biopsies due to fixation issues. Median, interquartile range (IQR) for mRSS change (0–52 W) for the ten participants was -2 (-9—7.5) and for the five with biopsies was -2.5 (-11—7.5). The correlation between Fibrosis Score and mRSS was R = 0.3; p = 0.674. Per 1-unit mRSS change (0–52 W), histologic parameters with the greatest associated changes were (OR, 95% CI, p-value): telangiectasia (2.01, [(1.31—3.07], 0.001), perivascular CD3 + (0.99, [0.97—1.02], 0.015), and % of CD8 + among CD3 + (0.95, [0.89—1.01], 0.031). Likewise, per 1-unit Fibrosis Score change, parameters with greatest changes were (OR, p-value): hyalinized collagen (1.1, [1.04 – 1.16], < 0.001), subcutaneous (SC) fat loss (1.47, [1.19—1.81], < 0.001), thickened intima (1.21, [1.06—1.38], 0.005), and eccrine entrapment (1.14, [1—1.31], 0.046). Belumosudil was associated with non-clinically meaningful mRSS improvement. The histologic features that significantly correlated with Fibrosis Score changes (e.g., hyalinized collagen, SC fat loss) were distinct from those associated with mRSS changes (e.g., telangiectasia and perivascular CD3 +). These data suggest that AI applied to SSc biopsies may be useful for quantifying pathologic features of SSc beyond skin thickness.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"33 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819845","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":"CCL23 is a potential biomarker for antineutrophil cytoplasmic antibody–associated vasculitis","authors":"Weiwei Hao, Qianqian Liu, Xiaoping Li, Yiran Xu, Wenjuan Guan, Lei Zhang, Fang Dong, Wenjun Cao, Shengyun Liu, Wei Li","doi":"10.1186/s13075-025-03552-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03552-5","url":null,"abstract":"The present cohort study aimed to evaluate the value of CCL23 in diagnosis, disease activity, and prognosis in patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV). CCL23 levels in serum samples from 317 patients with AAV and 83 healthy controls (HCs) were measured using a customized immune response kit. Patients with AAV had significantly elevated CL23 levels compared with HCs. CCL23 level was closely related to disease activity and was better than birmingham vasculitis activity score (BVAS) in distinguishing disease relapse from remission (area under curve: CCL23 = 0.942, BVAS = 0.84). Elevated CCL23 level was associated with poor prognosis within a 1 year follow-up period in patients with AAV (p = 0.0001). The ability of CCL23 to predict the poor prognosis of disease is better than that of five-factor score. Furthermore, elevated CCL23 levels were a risk factor for renal involvement (odds ratio = 1.722, p = 0.033), and were significantly related to serum creatinine (r = 0.381, p = 0.009) and eGFR (r = − 0.382, p = 0.01) at the time of diagnosis. High CCL23 level at diagnosis was associated with increased adverse outcomes during 1 year follow-up in patients with AAV with renal involvement (p = 0.0242). Elevated serum CCL23 level was closely related with disease activity and renal involvement in patients with AAV, can be a potential biomarker for diagnosis, and can predict prognosis in patients with AAV, especially adverse renal prognosis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"39 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813645","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":"Methotrexate-related drug reactions on kidneys and liver in rheumatoid arthritis: an analysis of spontaneous reports in EudraVigilance","authors":"Kai Khoroshun, Carsten Bantel, Falk Hoffmann, Kathrin Jobski","doi":"10.1186/s13075-025-03551-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03551-6","url":null,"abstract":"Methotrexate (MTX), a standard treatment for rheumatoid arthritis (RA), is known for its potential kidney and liver toxicity. Whether concomitant use of analgesics, possibly affecting the same organs, has an impact on the occurrence or course of adverse drug reactions (ADRs) remains unclear. We used all spontaneous reports (until 2022) of suspected ADRs associated with MTX in RA patients, from the EudraVigilance database, a spontaneous report system operated by the European Medicines Agency (EMA). We displayed case and treatment characteristics, stratified by the organ affected (kidneys, liver) and the outcome (fatal, non-fatal). We included a total of 10,319 reports (mean age: 62.3 years, 72.6% female). 365 and 1,082 were related to ADRs involving the kidneys and liver, respectively. Patients with ADRs on the kidneys were older and comedication (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, metamizole and corticosteroids) was more common than in cases with ADRs on the liver. More patients with kidney- than liver-related ADRs had a fatal outcome (21.1% vs. 5.8%). In fatal cases with ADRs on the kidneys and with ADRs on the liver comedication was more common compared to non-fatal cases. Liver dysfunction was reported nearly three times more often than renal impairment. However, the kidneys need to be especially watched for, since a fatal outcome was considerably more common in renal failure. More precise and standardized recommendations on renal function tests might be necessary to support physicians in the complex treatment of RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782585","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":"Discontinuation vs. continuation of concomitant methotrexate in patients with rheumatoid arthritis on certolizumab pegol: results from a randomised, controlled trial","authors":"Shuji Asai, Toshihisa Kojima, Hajime Ishikawa, Nobumasa Miyake, Masanari Kodera, Hisanori Hasegawa, Yasumori Sobue, Yasuhide Kanayama, Hiromi Shimada, Yuji Hirano, Toshihiko Hidaka, Takayoshi Fujibayashi, Takuya Matsumoto, Tomonori Kobayakawa, Hidekata Yasuoka, Takefumi Kato, Masahiro Hanabayashi, Yuko Kaneko, Masahiro Tada, Koichi Murata, Kenta Misaki, Masahiko Ando, Yachiyo Kuwatsuka, Mochihito Suzuki, Kenya Terabe, Shiro Imagama","doi":"10.1186/s13075-025-03548-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03548-1","url":null,"abstract":"The present non-inferiority study was designed to compare the effect of discontinuing versus continuing methotrexate (MTX) alongside certolizumab pegol (CZP) on maintaining low disease activity (LDA) in rheumatoid arthritis (RA) patients already stable on combination therapy. This multicentre, open-label, randomised, controlled trial included RA patients with sustained LDA (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with CZP + MTX. Patients were randomised 1:1 by computer to either continue MTX (CZP + MTX group) or discontinue MTX after a 12-week reduction period (CZP group) using a dynamic allocation strategy with the minimisation method. The primary endpoint was the proportion of patients maintaining LDA without a flare (i.e., a CDAI score > 10 or intervention with rescue treatments for any reason) at week 36 (24 weeks after MTX discontinuation). Non-inferiority is verified if the lower limit of the 90% confidence interval (CI) using normal approximation for the difference in the proportion of cases that maintained LDA at week 36 between the intervention group and control group exceeds the non-inferiority margin. All 84 screened patients were randomised to the CZP + MTX group (n = 41) and CZP group (n = 43), and were included in the efficacy analysis. Proportions (90% CI) of patients who maintained LDA at week 36 were 85.4% (76.3 to 94.4%) in the CZP + MTX group and 83.7% (74.5 to 93.0%) in the CZP group. The difference (90% CI) between the two groups was − 1.6% (-14.6 to 11.3%), with the lower limit of the 90% CI exceeding the non-inferiority margin of -18%. Reported adverse events were broadly similar between the two groups. The proportion of patients with gastrointestinal symptoms, as assessed by a self-administered questionnaire, was significantly lower in the CZP group than in the CZP + MTX group at week 36 (2.4% vs. 15.8%, P = 0.034). Discontinuing concomitant MTX in RA patients on CZP is clinically feasible for maintaining LDA. Japan Registry of Clinical Trials (jRCTs041200048).","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782572","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":"Cluster analysis reveals three clinical phenotypes of pulmonary artery hypertension associated with connective tissue diseases: insights into inflammation and immunity","authors":"Qianwen Wu, Dongyu Li, Huangshu Ye, Zhangdi Zhou, Yixin Zhang, Miaojia Zhang, Xiaoxuan Sun, Qiang Wang","doi":"10.1186/s13075-025-03545-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03545-4","url":null,"abstract":"Inflammation and immune mechanisms play a crucial role in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), though they remain inadequately understood. This study aimed to identify specific clinical phenotypes in CTD-PAH using inflammatory and immune markers through hierarchical cluster analysis. We conducted a single-center, retrospective cohort study of CTD-PAH patients from 2009 to 2024. Clinical variables, including neutrophil lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement C3 and C4, were analyzed to form clusters based on baseline characteristics, clinical outcomes, and treatment goals. Among 184 patients (95.1% female; median age 40.42 years), three distinct clusters were identified: Cluster 1 (vasculopathic phenotype) exhibited lower inflammatory activity but worse hemodynamic outcomes; Cluster 2 (vasculitic phenotype) had higher inflammatory activity with favorable hemodynamics; Cluster 3 (mixed phenotype) showed active inflammation and poor hemodynamic status. Most vasculitic patients were classified as systemic lupus erythematosus-associated PAH (SLE-PAH), which had a shorter course and higher prevalence of autoantibodies. The vasculopathic and mixed phenotypes were common in scleroderma-related PAH (SSc-PAH), undifferentiated CTD- related PAH (UCTD-PAH), and mixed CTD- related PAH (MCTD-PAH), associated with poorer treatment outcomes and survival rate. Distinct clinical phenotypes in CTD-PAH correlate with inflammatory activity and hemodynamic status, influencing treatment responses and prognosis. Inflammation and immune mechanisms are essential for the development of CTD-PAH. Three distinct phenotypes in CTD-PAH were identified through cluster analysis. Distinct phenotypes correlate with inflammatory and hemodynamic status, influencing treatment responses and prognosis. Identifying disease phenotypes might improve the management algorithm for CTD-PAH.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"108 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782587","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":"Infrapatellar fat pad as a source of biomarkers and therapeutic target for knee osteoarthritis","authors":"Betzabeth Pereira Herrera, Kaj Emanuel, Pieter J. Emans, Martijn van Griensven, Berta Cillero-Pastor","doi":"10.1186/s13075-025-03517-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03517-8","url":null,"abstract":"Osteoarthritis (OA) is a multifactorial and highly prevalent disease in elderly adults; however, its pathogenesis, diagnosis, and treatment are unmet needs nowadays. Research efforts have focused on elucidating the molecular mechanisms involved in the pathogenesis, onset, and progression of OA to facilitate early detection and effective therapeutic approaches. Infrapatellar fat pad (IPFP) represents a promising novel source of OA biomarkers given that it is an active player in OA. This review aims to investigate the current literature regarding the potential of the IPFP as a source of diagnostic and prognostic biomarkers for OA as well as potential target for novel therapies. A literature search was conducted in the PubMed database in June 2024. We included cross-sectional and longitudinal studies based on IPFP from human OA patients, oriented in the identification of imaging, biochemical, and molecular biomarkers in the IPFP. After screening and evaluation, we included a total of 61 studies. Most of the imaging publications (n = 47) on IPFP are based on magnetic resonance imaging (MRI) that revealed potential semiquantitative and quantitative imaging biomarkers linked to inflammation, fibrosis, pain, and joint degeneration imaging parameters. Biochemical and molecular studies (n = 14) pointed out an increase in interleukin-6 (IL-6), fatty acid-binding protein 4 (FABP4), adiponectin, and lysophosphatidylcholine (LysoPC) in the IPFP during OA progression. Imaging, biochemical, and molecular studies indicate OA potential biomarkers in the IPFP related to inflammation, lipid dysregulation, and fibrosis. The combination of imaging and biochemical biomarkers could provide a better prediction of OA onset and the identification of OA progressors at an early stage. The IPFP study could also reveal potential therapeutic targets with the vision of better precision medicine.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"34 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782573","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":"Concomitant Sjögren’s disease in patients with NMOSD: impacts on neurologic disease severity and recurrence","authors":"Wanqing Wu, Wenbo Yang, Bo Deng, Helian Li, Xiaoni Liu, Hai Yu, Xiang Zhang, Minrui Liang, Xiangjun Chen","doi":"10.1186/s13075-025-03538-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03538-3","url":null,"abstract":"We aimed to characterize the phenotype of neuromyelitis optica spectrum disorder (NMOSD) in the presence and absence of Sjogren's disease (SjD) and to develop a predictive nomogram to evaluate the risk of coexisting SjD within a single tertiary-center cohort of NMOSD patients. Paraclinical and clinical features of patients with SjD were compared between NMOSD patients with SjD and those without SjD. Zstats v1.0 was utilized to randomly allocate participants into a derivation group (108 patients) and a validation group (47 patients) at a ratio of 7:3. Logistic regression analysis was used to assess the effectiveness of our predictive model, and a nomogram was created to illustrate the findings. A total of 155 NMOSD patients who were serologically positive for AQP4-IgG were cross-sectionally recruited (70 NMOSD patients with SjD [45.16%] and 85 NMOSD patients without SjD [54.84%]). Independent predictors of coexisting SjD were age upon recruitment (P = 0.002); Expanded Disability Status Scale (EDSS) score (P = 0.023); blood white blood cell (WBC) count (P = 0.049); and rheumatoid factor (RF) (P = 0.049), anti-SSA (Ro), and anti-SSB (La) antibody positivity (P < 0.001; P = 0.012). The nomogram had an area under the receiver operating characteristic (ROC) curve (AUC) (95% confidence interval [CI]) of 0.95 (0.89, 1.00) in the derivation cohort and 0.91 (0.79, 1.00) in the validation cohort. Survival curve analysis revealed that the EDSS score in the NMOSD patients with SjD was associated with clinical relapse, and these patients reached an EDSS score of 4.0 earlier than those without SjD. NMOSD patients with SjD manifested more severe disease at attack and relapsed earlier than those without SjD. The nomogram established by combining age upon recruitment; EDSS score; blood WBC count; and RF, anti-SSA (Ro), and anti-SSB (La) antibody levels can significantly predict the risk of NMOSD combined with SjD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"23 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782580","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}