Arthritis Research & Therapy最新文献

{"title":"nCD64 index as a new early predictive biomarker for macrophage activation syndrome in adult-onset still’s disease","authors":"Tongxin Wu, Liyang Gu, Bisheng Shi, Yiwei Wu, Jinming Yang, Zhengting He, Xi He, Xinyun Zhu, Liangjing Lu, Xiaoxiang Chen, Ruru Guo","doi":"10.1186/s13075-025-03611-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03611-x","url":null,"abstract":"Macrophage activation syndrome (MAS) represents a severe and potentially life-threatening complication of adult-onset Still’s disease (AOSD), necessitating the identification of sensitive and specific biomarkers for early diagnosis. Our study found significantly elevated CD64 mRNA expression in neutrophils of AOSD patients compared to healthy controls (p = 0.029). The neutrophil CD64 index (nCD64 index) positively correlated with key clinical manifestations, including splenomegaly, sore throat, pulmonary infiltrates, and pericarditis. Effective treatments led to a rapid and significant decrease in the nCD64 index (p < 0.001). Logistic regression showed that an elevated nCD64 index is a risk factor for MAS (OR = 1.073, p = 0.003). ROC curve analysis indicated that the nCD64 index reliably distinguished AOSD patients with MAS (AUC = 0.877; cutoff = 32.09; p < 0.001) and combined utilization of nCD64 index, ferritin, and sIL-2R demonstrated a strong predictive value. Correlations with hospitalization length (r = 0.382, p < 0.001) and maximum glucocorticoid dose (r = 0.326, p = 0.003) were also observed. Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MAS in patients with an nCD64 index > 32.09 (p < 0.001). These findings suggest the nCD64 index is a promising biomarker for early identifying AOSD patients at risk of MAS, aiding in timely diagnosis and management.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"21 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594242","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":"Roles of JAK-STAT signaling and granulocyte–macrophage colony-stimulating factor in the development of osteitis and bone microstructure changes in rheumatoid arthritis","authors":"Tsuneyasu Yoshida, Yoshiki Murotani, Koichi Murata, Hirohiko Imai, Takeshi Iwasaki, Yoichi Nakayama, Masao Katsushima, Mirei Shirakashi, Ran Nakashima, Ryu Watanabe, Kosaku Murakami, Hajime Yoshifuji, Akio Morinobu, Motomu Hashimoto","doi":"10.1186/s13075-025-03597-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03597-6","url":null,"abstract":"Osteitis on magnetic resonance imaging (MRI) and bone microstructure changes (BMC) on high-resolution peripheral quantitative computed tomography (CT) are the earliest signs of arthritis, preceding the development of bone erosion on X-ray in rheumatoid arthritis (RA). Recently, a Janus kinase (JAK) inhibitor, baricitinib, reportedly suppresses these early changes. This study aimed to elucidate the underlying molecular mechanism of osteitis and BMC using an animal model of RA and human samples. Osteitis and BMCs were assessed via MRI and micro-CT, respectively, in zymosan-treated SKG mice. Bone marrow (BM) cells were analysed via flow cytometry. JAK‒signal transducer and activator of transcription (STAT) cytokine expression was measured via performing quantitative PCR. Zymosan-treated SKG mice received baricitinib, anti-granulocyte‒macrophage colony-stimulating factor (GM-CSF) antibodies, or recombinant GM-CSF (r-GM-CSF). r-GM-CSF was also used in an in vitro osteoclast differentiation assay. Osteoclast differentiation was also investigated with human monocytes. Osteitis and BMCs occurred prior to arthritis in SKG mice. Granulocyte‒macrophage-lineage cells and osteoclast precursor cells (OCPs) expanded in the inflammatory BM. Receptor activator of nuclear factor kappa-B ligand-positive osteoclasts were observed at BMC sites. The expression of GM-CSF, a JAK‒STAT cytokine, was upregulated in osteitic BM. Both baricitinib and anti-GM-CSF antibodies suppressed osteitis and BMCs, whereas r-GM-CSF exacerbated these changes. In vitro addition of r-GM-CSF to osteoclast differentiation assay markedly increased the number and size of osteoclasts, especially when added in the late phase of osteoclast differentiation both in mice and humans. GM-CSF drives osteitis and BMCs by increasing granulocyte‒macrophage-lineage cells and OCPs and promoting osteoclast differentiation. Targeting GM-CSF is a potential therapeutic strategy to prevent early radiographic changes in RA. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594245","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 association between metabolic syndrome severity and frailty risk in patients with rheumatoid arthritis: a cross-sectional study","authors":"Yuefang Liu, Yan Xin, Weiwei Wang, Wei Feng, Lei Zhang, Yang Zhao, Youzhuang Zhu","doi":"10.1186/s13075-025-03612-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03612-w","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune disease in which systemic inflammation may put individuals at increased risk of developing frailty and metabolic syndrome (MetS). However, the relationship between MetS severity and frailty remains poorly understood in individuals with RA. Further, traditional MetS diagnostic methods do not assess severity and thus may lack sensitivity in capturing subtle metabolic abnormalities. In this cross-sectional study, data from the National Health and Nutrition Examination Survey (2003–2018) were used to construct weighted multivariable logistic regression models to explore the risk association between MetS severity and frailty in RA patients. Restricted cubic spline analysis was used to examine non-linear correlation between MetS severity and frailty. We also conducted subgroup analyses and interactions as well as sensitivity analysis to evaluate the robustness of results. A total of 802 RA patients were included in this study, among whom 442 were identified as frail (52.05%). RA patients with higher MetS severity had significantly increased frailty risk [adjusted odds ratio (aOR): 1.26; 95% CI: 1.09–1.46; p = 0.003]. There was a non-linear relationship between MetS severity and frailty (p for overall < 0.001; p for non-linear < 0.001), with an inflection point at 0.089. When MetS z-score was < 0.089, there was no significant association between MetS z-score and frailty (p > 0.05), whereas the association was positive for scores ≥ 0.089 (aOR: 1.68; 95% CI: 1.30–2.17; p < 0.001). The risk of frailty increased significantly with increasing MetS severity among alcohol drinkers (aOR: 1.43; 95% CI: 1.19–1.71; p < 0.001) compared with non-drinkers (aOR: 0.97; 95% CI: 0.73–1.29; p = 0.085). Sensitivity analysis confirmed robustness of the association between MetS severity and risk of frailty. We identified a significant association between MetS severity and frailty risk in patients with RA. As MetS severity increased, the risk of frailty was higher among alcohol drinkers compared to non-drinkers. Clinicians should enhance frailty screening and management in patients with RA by incorporating assessments of MetS severity into routine practice.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"10 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594244","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":"Investigation of serum biomarkers in rheumatoid and psoriatic arthritis patients for disease-specific signatures","authors":"James D Veale, Áine Gorman, Douglas J Veale, Ursula Fearon, Carl Orr, Viviana Marzaioli","doi":"10.1186/s13075-025-03608-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03608-6","url":null,"abstract":"Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are systemic auto-immune diseases of unknown aetiology that lead to systemic inflammation and synovial joint destruction. Identification of specific serum proteins that selectively regulate these diseases, or which precede disease development could have great potential as disease biomarkers and predictors. Serum levels of C-reactive protein (CRP), sICAM-1, sVCAM-1, Serum amyloid A (SAA), Matrix metalloproteinases (MMPs 1, 3 and 9) and metabolic markers: Active Glucose-dependent Insulinotropic polypeptide (GIP), active Glucagon-like peptide-1 (GLP-1), C-Peptide, Glucagon, Insulin, Leptin, Pancreatic Polypeptide (PP) were measured by Meso Scale Discovery (MSD) multiplex analysis assay. Serum levels of sICAM-1, MMP1, MMP3, PP, c-Peptide, CRP and SAA were specifically upregulated in RA, but not in PsA disease, displaying high sensitivity (ROC curves). In the early phase of the disease, these markers may be suitable for discriminating RA from PsA patients. Differences in sex, BMI, and disease activity were observed. This is the first study which directly compare serum metabolic markers between diseases and identifies specific disease signatures between RA and PsA. In addition, this study identified that CRP, SAA, GLP-1, GIP-1, Leptin and PP serum protein precede disease onset, as they are already altered in the serum of ‘individuals at risk’ of developing RA. Of these, CRP, SAA, Leptin and PP might predict IAR conversion to RA+, thus making them suitable candidates for disease prediction. Altogether, this study identifies selective serum markers associated with RA and PsA, which are pathotype-specific and are predictors of RA disease onset.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"109 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594241","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":"Receptor activator of nuclear factor-kappa B ligand-derived microglia healing peptide 1-AcN inhibits osteoarthritis progression in mice","authors":"Yuji Fukuda, Munehisa Shimamura, Yuki Etani, Takaaki Noguchi, Takuya Kurihara, Atsushi Goshima, Taihei Miura, Makoto Hirao, Nagahiro Ochiai, Nan Ju, Atsushi Sugimoto, Takashi Kanamoto, Ken Nakata, Seiji Okada, Kosuke Ebina","doi":"10.1186/s13075-025-03609-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03609-5","url":null,"abstract":"Osteoarthritis (OA) is a degenerative disease characterized by subchondral bone sclerosis, chronic inflammation, and cartilage degradation. Abnormal mechanical stress by meniscal deviation activates osteoclasts and induces the release of transforming growth factor-beta (TGF-β), which promotes mesenchymal stem cell (MSC)-mediated type H angiogenesis and osteogenesis, contributing to bone sclerosis and cartilage damage. Subsequently, macrophages recognize cartilage-derived damage-associated molecular patterns (DAMPs) via Toll-like receptor 4 (TLR4), polarizing into the pro-inflammatory M1 phenotype, thereby exacerbating synovitis and cartilage loss. We developed Microglia Healing Peptide 1 with N-terminal acetylation and C-terminal amidation (MHP1-AcN), a modified peptide derived from receptor activator of nuclear factor-kappa B ligand (RANKL), exhibiting both anti-osteoclastic and anti-inflammatory properties. This study aimed to evaluate the therapeutic potential of MHP1-AcN in a murine OA model and elucidate its underlying mechanisms. OA was induced in mice via destabilization of the medial meniscus (DMM) surgery. Mice were randomly assigned to three groups (n = 8/group): Sham (sham surgery + saline), Vehicle (DMM + saline), and MHP1-AcN (DMM + MHP1-AcN). MHP1-AcN (600 µg) was administered intraperitoneally five times per week from a day after surgery. Knee joints were harvested at 2, 4, and 8 weeks post-surgery. In vitro, the effects of MHP1-AcN were assessed on osteoclast differentiation, inflammatory cytokine expression, and M1/M2 macrophage polarization using mouse bone marrow-derived macrophages. Additionally, its effects on TGF-β-induced osteogenic differentiation of bone marrow-derived MSCs (BMMSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated. MHP1-AcN markedly suppressed key pathological features of OA in vivo, including synovial inflammation, osteoclast-driven subchondral bone remodeling, aberrant angiogenesis, and cartilage degeneration. In vitro, MHP1-AcN effectively inhibited TLR4-mediated inflammatory cascades by reducing M1 macrophage polarization and inflammasome activation. Despite being derived from RANKL, MHP1-AcN supressed RANKL-induced osteoclastogenesis through NF-κB pathway suppression. Furthermore, MHP1-AcN attenuated TGF-β-induced osteogenic and angiogenic activities via Smad2 signaling inhibition in BMMSCs and HUVECs. MHP1-AcN attenuates OA progression by modulating multi-pathways including aberrant bone remodeling, angiogenesis, and macrophage polarization, representing a promising disease-modifying therapeutic candidate for OA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"109 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586878","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":"UBE2D1 as a key biomarker in systemic juvenile idiopathic arthritis: a new perspective on diagnosis and disease activity assessment","authors":"Qiang Luo, Han Hao, Luo Xiwen, Xiang Qiu, Dawei Liu, Yun Liu, Fengning Li, Kening Lu, Xiya Luo, Chenxi Ma, Xiaodong Zhao, Yunfei An, Xuemei Tang","doi":"10.1186/s13075-025-03606-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03606-8","url":null,"abstract":"Early diagnosis is crucial for reducing disability and improving long-term prognosis in patients with systemic Juvenile Idiopathic Arthritis (sJIA), but it remains a significant challenge. This study aims to identify non-invasive biomarkers with superior diagnostic efficacy for sJIA. To predict early potential biomarker candidates and pathogenic mechanisms for sJIA, we performed scRNA-seq and Bulk RNA-seq on PBMCs from the Chinese sJIA cohort. The findings were validated through in vitro experiments and cell sequencing. We also established the relationship between UBE2D1 and other systemic diseases to determine possible complications of sJIA. Using scRNA-seq and Bulk RNA-seq, we discovered that UBE2D1 expression is closely related to disease activity levels, specifically in classical monocytes from sJIA patients. Functional enrichment suggested that UBE2D1 could enhance disease progression by activating NLRs. Follow-up data indicated a significant reduction in UBE2D1 expression and monocyte numbers before and after treatment. Pseudotime analysis revealed that UBE2D1 expression is initially high during monocyte development. Western blot results showed increased levels of UBE2D1 and NLRs marker proteins, which decreased upon introducing UBE2N and NF-κB inhibitors. Co-IP suggested that UBE2D1 mediates the activation of the NLRs pathway by interacting with IKB-α. The UBE2D1 complication map indicates that UBE2D1 might contribute to the development of various diseases across 17 different systems, including autoimmune diseases, the digestive system, and ocular conditions. Our findings provide insights into the biological mechanisms of sJIA, indicating that UBE2D1, which is highly expressed in monocytes, may represent a candidate biomarker for early diagnosis and a potential method for clinical treatment strategies, pending further validation.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"29 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586893","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":"Association between rheumatoid arthritis and kidney stones: A cross-sectional study of NHANES 2007–2020","authors":"Gaoyuanzhi Yue, Yanhua Yan, Xueqing Zeng, Renfei Liu, Tao He, Yongda Liu","doi":"10.1186/s13075-025-03604-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03604-w","url":null,"abstract":"Kidney stones (KS) and Rheumatoid arthritis (RA) are common diseases, but their association remains unclear. Our research aims to investigate a possible link between RA and KS. This study investigates the relationship between RA and KS prevalence and uses data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2020. RA and KS diagnoses were self-reported via validated questionnaires. Weighted logistic regression was used to assess the independent associations between RA and KS (adjustments for age, sex, race, education level, PIR, marital status, smoke status, alcohol status, BMI, diabetes, hypertension, total energy intake, total water intake, Scr, BUN, total cholesterol, triglycerides, HDL, serum uric acid). Moreover, we executed subgroup analyses and interaction assessments to ensure the robustness and reliability of these results. 19,904 participants (≥ 20 years) were included in the study, including 1,477 RA patients. The rate of KS (17.009% vs. 8.123%, p < 0.001) in the RA group was higher than that in the non-RA group. After correcting for all covariates, we found a positive association between RA and KS (OR = 1.770, 95% CI: 1.418–2.209). In addition, a strong correlation between RA and KS persisted across all stratified subgroup analyses. In adults in the United States, RA was significantly associated with higher KS prevalence. Nevertheless, the cross-sectional design restricts causal inference. In the future, additional research is required to confirm this association.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"106 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586890","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":"Insights into the detection of AMPA cross-reactivity: comparing cyclic peptide- to protein-based assays","authors":"Roxane Biersteker, Aegli Athanasiadou, Stef van der Meulen, Tineke J. van Wesemael, Linda M. Slot, Theresa Kissel, René E. M. Toes, Leendert A. Trouw, Diane van der Woude","doi":"10.1186/s13075-025-03591-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03591-y","url":null,"abstract":"Autoantibodies targeting antigens carrying distinct post-translational modifications (PTMs), including citrullinated, carbamylated, and acetylated residues, are characteristic for rheumatoid arthritis (RA). These anti-modified protein antibodies (AMPAs) are typically detected using enzyme-linked immunosorbent assays (ELISAs), with peptides or protein antigens carrying these modifications. AMPAs exhibit significant cross-reactivity towards multiple PTMs, and increased cross-reactivity before disease onset may serve as a biomarker of disease progression. However, the impact of antigen backbone variations on cross-reactivity detection remains unclear. Therefore, we investigated how PTM-backbone variations affect AMPA-reactivity detection. Sera of 608 RA patients from the Early Arthritis Clinic (EAC) were measured for AMPA reactivity using modified fetal calf serum (FCS)- and cyclic peptide (CXP2)-based ELISAs. To investigate cross-reactivity patterns, we isolated AMPAs from serum using either modified FCS or peptides and assessed the reactivity of the isolated antibodies towards three different PTMs. CXP2-based assays reveal a higher proportion of patients with serum reactivity against multiple PTM residues, while FCS-based assays exhibit a more restricted serological profile. When comparing responses to citrullinated versus carbamylated backbones, 61.2% of samples reacted to both PTM-residues on CXP2, while on FCS this percentage significantly decreased to 54.0%. The antigen backbone also influences AMPA isolation, as modified FCS captures AMPAs with a more restricted, less cross-reactive epitope recognition profile compared to those captured with modified peptides. Antigen backbones influence the detection of AMPA cross-reactivity. Gaining a better understanding of how PTM backbones affect this detection could provide insights into the structural basis of AMPA reactivity, and refine data interpretation by highlighting how assay choice influences results.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"7 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568821","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":"Sicca manifestations and lymphoproliferation in hepatitis C virus: effects of direct acting antiviral therapy on dryness and B-cell activity compared to Sjögren’s disease","authors":"Amina Maher, Mohamed Tharwat Hegazy, Tareq M. Algarf, Manar A. Abdul-Aziz, Luca Quartuccio, Naguib Zoheir, Salvatore De Vita, Gaafar Ragab","doi":"10.1186/s13075-025-03605-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03605-9","url":null,"abstract":"Hepatitis C virus (HCV) can be associated with sicca manifestations. To study the effect of direct-acting antivirals (DAAs) on sicca manifestations in HCV-infected patients and the difference between those patients and others with HCV without dryness & Sjögren’s disease (SjD). We studied 60 patients in 3 groups: Group 1 (20 HCV + sicca), group 2 (20 HCV without sicca), and group 3 (20 SjD). Groups 1 and 2 received DAAs according to the Egyptian Ministry of Health protocols and were evaluated before and after treatment. Group 3 was evaluated once. Our study evaluated the patients by both subjective and objective methods. All HCV cases had sustained viral response (SVR). Comparing the characteristics of groups 1 (before treatment) & 3: Group 1 had a higher frequency of RF, cryoglobulins, and polyclonal-hypergammaglobulinemia (P-values 0.021, 0.003, and ˂0.001 respectively). Group 3 had higher scores of VAS dry eye, VAS dry mouth, VAS fatigue, and VAS pain than group 1 (P-values ˂0.001 in all). Group 3 also had a higher frequency of Anti-Ro and Anti-La (P-values < 0.001). Group-1 before DAAs treatment had higher markers denoting B-cell hyperactivity [higher Rheumatoid factor (RF), cryoglobulins, and beta2-microglobulins (β2M)] compared to group-2 which improved markedly after SVR. This supports that group 1 is further ahead in the direction of lymphoproliferation. Group 1 patients after SVR showed marked improvement in VAS dry eye, VAS dry mouth, VAS fatigue, VAS pain, ESSPRI, and ESSDAI (P-values ˂0.003, ˂0.002, ˂0.016, ˂0.001, ˂0.002, and ˂0.014 respectively). There was a significant improvement in RF, and serum β2M levels (after SVR), (P-values ˂0.013, and 0.001 respectively). Group 1 is further ahead in the direction of lymphoproliferation than group 2 with higher statistically significant serum β2M and polyclonal serum protein electrophoresis (P-values 0.006 and 0.047 respectively). HCV patients with sicca manifestations treated by DAAs showed significant clinical and immunological improvements. The difference between group 1 (before and after SVR) and group 3 supports the notion that they are two different entities, with different characteristic features. Sicca manifestations improved after the eradication of HCV.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568818","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":"Gut microbiome dysbiosis accelerates osteoarthritis progression by inducing IFP-SM inflammation in “double-hit” mice","authors":"Su Liu, Huihui Xu, Lijin Liu, Wenjing Ma, Hao Fan, Fei Liu, Ze Wei, Jing Hao, Zhifa Zheng, Lina Zhao, Bo Yang, Zhihong Wu","doi":"10.1186/s13075-025-03602-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03602-y","url":null,"abstract":"This study investigates the complex interplay between gut microbiome dysbiosis and systemic inflammation as a critical risk factor in the pathogenesis of osteoarthritis (OA). Furthermore, it elucidates the role of gut microbiota (GMB) dysbiosis in driving OA progression. A refined “double-hit” murine model was developed to explore this relationship. The first intervention involved inducing gut microbiota dysbiosis through the administration of colistin and Escherichia coli, followed by surgical destabilization of the medial meniscus (DMM) to induce joint instability. The composition of the gut microbiota was analyzed using 16 S rRNA sequencing. Gut permeability was assessed via RT-PCR and immunofluorescence (IF), while mRNA sequencing was employed to examine alterations in gene expression. Treatment with colistin and E. coli significantly altered the gut microbiota composition, characterized by a marked increase in the absolute abundance of Firmicutes and a concomitant reduction in Bacteroidota and the Bacteroidota/Firmicutes (B/F) ratio. At the genus level, the absolute abundances of Muribaculaceae, Rikenellaceae_RC9_gut_group, and Roseburia were significantly diminished. GMB dysbiosis led to the downregulation of intestinal tight junction proteins, including ZO-1 and Occludin, resulting in increased intestinal permeability. Consequently, serum levels of lipopolysaccharide (LPS) were significantly elevated, indicating LPS translocation from the gut into systemic circulation. Notably, GMB dysbiosis markedly exacerbated OA progression, as evidenced by accelerated cartilage degeneration, increased osteophyte formation, and reduced bone mineral density (BMD). The OARSI scoring system revealed that OA severity in both colistin and E. coli treatment groups was significantly higher than in the control group. Additionally, GMB dysbiosis promoted the expression of inflammation-related genes in the synovium and induced M1 polarization of macrophages, demonstrated by the upregulation of CD86 and an elevated CD86/CD206 ratio. Correlation analyses indicated that Bacteroidota and the B/F ratio were positively associated with intestinal barrier integrity and negatively correlated with OA progression. In contrast, Firmicutes exhibited a positive correlation with inflammation and OA deterioration. These findings collectively underscore the critical role of GMB dysbiosis in modulating intestinal permeability, systemic inflammation, and OA pathogenesis. The protective effects of Bacteroidota and the B/F ratio, as well as the detrimental impact of Firmicutes, highlight potential therapeutic targets for mitigating OA progression through GMB modulation.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568822","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}