Arthritis Research & Therapy最新文献

{"title":"Investigating potential biomarkers associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis using Mendelian randomization and transcriptomic analysis","authors":"Yujia Wang, Zhimin Chen, Kaiqi Huang, Keng Ye, Shiwei He, Yanfang Xu, Hong Chen","doi":"10.1186/s13075-025-03630-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03630-8","url":null,"abstract":"Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disorder characterized by multi-organ involvement. Early identification and accurate diagnosis of AAV is crucial for improving prognosis. However, research on biomarkers associated with AAV is limited. This study aimed to explore novel biomarkers for AAV through transcriptomic data analysis and Mendelian randomization (MR). AAV-related datasets (GSE104948 and GSE108109) were analyzed. Differentially expressed genes (DEGs) between AAV and normal groups were identified in the GSE104948 dataset. MR analysis was then used to investigate the causal relationship between DEGs and AAV. Genes with a significant causal relationship were selected as candidate genes for further analysis. Machine learning algorithms, ROC curve analysis, and expression evaluation were employed to screen for biomarkers. Additionally, artificial neural networks (ANNs) were constructed, enrichment analysis and immune infiltration were performed, a molecular regulatory network was established, and potential drugs were predicted. Finally, immunofluorescence assays validated the significance of these genes in renal biopsies from patients with ANCA-associated glomerulonephritis. PDK4, PSMB10 (IVW, OR > 1, P < 0.05), PPARGC1A, and FN1 (IVW, OR < 1, P < 0.05) were identified as biomarkers. Specifically, PDK4 and PPARGC1A exhibited significant down-regulation in the AAV group compared to the normal group, while FN1 and PSMB10 showed an opposite pattern. The ANN created based on biomarkers exhibited a robust predictive capacity for assessing the risk of AAV. Furthermore, co-enrichment of PDK4 and PPARGC1A was observed in ‘butanoate metabolism’, and ‘fatty acid metabolism’. Meanwhile, there was a strong positive correlation observed between naive B cells and PDK4, while a substantial negative correlation was found with PSMB10. Molecular regulatory network results demonstrated that XIST exerted regulatory effects on PDK4, FN1, and PPARGC1A through hsa-miR-103a-3p, hsa-miR-1271-5p, and hsa-miR-23a-3p simultaneously. Besides, this study revealed that 19 drugs exhibited potential targeting capabilities towards 4 biomarkers, such as dacarbazine, dichloroacetate, and bortezomib. Validation in renal biopsies from patients with ANCA-associated glomerulonephritis confirmed decreased glomerular expression of PDK4 and PPARGC1A, and increased expression of FN1 and PSMB10 compared to controls. PDK4, PPARGC1A, FN1, and PSMB10 were identified as biomarkers causally related to AAV, offering potential for both precise diagnosis and targeted treatment strategies. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901873","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":"Analysis of epigenetic biomarkers for diagnosis and assessment of severity in rheumatoid arthritis: a cross-sectional study","authors":"Arkaitz Mucientes, Gracia María Martín Núñez, Natalia Mena-Vázquez, Jose Manuel Lisbona-Montañez, Sara Manrique-Arija, Andrés González-Jiménez, Patricia Ruiz-Limón, Aimara Garcia-Studer, Fernando Ortiz-Márquez, Laura Cano-García, Antonio Fernández-Nebro","doi":"10.1186/s13075-025-03628-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03628-2","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease influenced by genetic, environmental, and epigenetic factors. Epigenetic modifications, particularly DNA methylation, in immune-related genes may impact inflammation and immune responses. This study aims to analyze methylation patterns in RA patients and controls to identify diagnostic and prognostic epigenetic biomarkers. A cross-sectional study of a prospective cohort comprising 32 patients (16 with severe RA, 16 with nonsevere RA) and 32 healthy controls (discovery cohort) was performed. Severity was defined as a cumulative 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) ≥ 3.2, positive rheumatoid factor (RF) and anti–citrullinated peptide antibody (ACPA) values, and a high Collinsella aerofaciens count (OTU ≥ 0.15). Whole genome methylation analysis was performed using the Infinium Methylation EPIC BeadChip kit. Subsequently, validation by pyrosequencing (PyroMark Q48) was performed for the differentially methylated positions (DMPs) selected both in the discovery cohort and in the remainder of the inception cohort (78 patients and 78 controls). More than half of the participants were women (≥ 75%), and the mean age was 56 years. At whole genome level, an epigenetic signature was associated with both RA and severity of RA. Pyrosequencing confirmed that methylation levels at CpG sites in TBC1D22A, PRHOXNB, ALLC, and PRG2 genes were associated with RA or severity of RA. The novel association between hypermethylation in TBC1D22A and RA was subsequently confirmed in an independent cohort. Our results indicate that the level of DNA methylation in validated DMPs is associated with RA. Thus, these methylation levels are potential biomarkers for the diagnosis, prognosis and severity of RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797076","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":"Trim21 deficiency alleviates osteoporosis by inhibiting osteoclast differentiation through regulating Txnip","authors":"Ya-Chen Peng, Yong-Sheng Ye, Qin-Xiao Hu, Zhi-Quan Hao, Zhen-Yan Li, Luo-Yong Jiang, Hao-Ran Peng, Ri-Xu Liu, Zhen-Gang Zha, Huan-Tian Zhang","doi":"10.1186/s13075-025-03624-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03624-6","url":null,"abstract":"The tripartite motif containing 21 (Trim21), an E3 ubiquitin ligase, plays a crucial role in the progression of various skeletal diseases, particularly in osteoporosis. In our previous study, Trim21 deficiency was shown to exert dual effects by suppressing bone resorption and enhancing osteogenesis. However, the specific mechanism by which Trim21 inhibits osteoclast (OC) differentiation remains unclear. In this study, we utilized a myeloid cell–specific conditional knockout model of Trim21 to investigate the underlying regulatory mechanisms. OC-specific Trim21 knockout mice were generated and subjected to ovariectomy (OVX) to establish a model of postmenopausal osteoporosis. Bone mass and OC activity were then evaluated using micro-computed tomography (micro-CT) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow-derived macrophages (BMMs) were induced to differentiate into OCs, and gene expression levels were detected by qRT-PCR. Additionally, proteomic analysis was performed to identify downstream regulatory proteins influenced by Trim21. OC-specific Trim21 deletion alleviated OVX-induced bone loss by inhibiting bone resorption and preserving bone mass. Myeloid-specific Trim21 deletion impaired OC differentiation and suppressed the expression of key OC markers. Thioredoxin-interacting protein (Txnip), was identified as a downstream effector regulated by Trim21. Trim21 deletion attenuates osteoporosis-induced bone loss, likely by suppressing osteoclast differentiation through modulation of Txnip, thereby presenting a potential novel therapeutic target for osteoporosis treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"15 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756440","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":"Oscillometric, greyscale- and novel color-Doppler-ultrasound indices of macrovascular damage in Sjögren’s: the SICARD cohort study","authors":"Konstantinos Triantafyllias, Mirjam Bach, Sebastian Bögel, Muthuraman Muthuraman, George Bertsias, Dimitrios Boumpas, Raoul Bergner, Markus Schepers, Andreas Schwarting","doi":"10.1186/s13075-025-03625-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03625-5","url":null,"abstract":"To assess for the first time a combination of oscillometric, greyscale- and novel color-Doppler ultrasound (US) indices of carotid and aortic damage in patients with primary Sjögren’s syndrome (pSS). Moreover, to examine associations of these markers with patient and disease-characteristics, as well as with a traditional cardiovascular (CV) risk score (SCORE) and its EULAR-modified version (mSCORE). Greyscale and color-Doppler indices [resistance (RI)- and pulsatility (PI)-index], as well as markers of atherosclerosis [Intima-Media-Thickness (cIMT), plaques, and cumulative calcification surface], were examined in the common- (CCA) and internal- (ICA) carotid arteries of pSS patients and healthy controls. The gold standard oscillometric marker of aortic stiffness (carotid-femoral pulse wave velocity; cfPWV) and the traditional SCORE/mSCORE, were also assessed. We recruited 119 pSS-patients and 97 controls. Patients exhibited significantly higher cfPWV (padj = 0.025), cIMT (padj < 0.001), and calcification area (p = 0.013), compared to controls. According to mSCORE, 5.7% of the patients had high CV risk. However, cfPWV and carotid-sonography revealed increased aortic stiffness in 45.4% and carotid atherosclerosis in 69.2%, respectively. Among pSS-patients, cfPWV correlated with C-reactive-protein (rho = 0.325, p < 0.001), erythrocyte-sedimentation-rate (rho = 0.271, p = 0.003), and traditional CV-risk factors (age, cholesterol, systolic blood pressure: all; p < 0.01). ICA-RI and ICA-PI were higher in patients with further (non-rheumatological) autoimmune diseases (both; p < 0.05). In the largest cfPWV/US-cohort examined to date, pSS-patients had significantly higher aortic stiffness and atherosclerosis than controls. Aortic stiffness was predicted by systemic inflammation, alongside traditional CV risk factors. cfPWV and carotid-US may help identify subclinical end-organ disease and atherosclerosis and thus assist CV/CVB-screening in pSS. DRKS00031470. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"145 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756451","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 diagnostic utility of lung ultrasound in the assessment of interstitial lung disease associated with rheumatoid arthritis","authors":"Shaoyu Zheng, Zexuan Zhou, Guangzhou Du, Qingzi Chen, Shaoqi Chen, Jianqun Lin, Shijian Hu, Weijin Zhang, Kedi Zheng, Jinghua Zhuang, Meigan Huang, Barbara Ruaro, Cosimo Bruni, Anna-Maria Hoffmann-Vold, Marco Matucci-Cerinic, Daniel E. Furst, Yukai Wang","doi":"10.1186/s13075-025-03626-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03626-4","url":null,"abstract":"To investigate the diagnostic accuracy of lung ultrasound (LUS) for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). This retrospective study included patients over 18 years with RA evaluated at the Department of Rheumatology and Immunology of Shantou Central Hospital. All patients underwent chest high-resolution computed tomography (HRCT) and LUS within one month. The LUS was performed in a total of 50 scanning sites (ScS), and the number of B-lines present in each ScS was counted and summed up as B-lines score. A positive judgement was given on LUS when the B-lines score exceeded 10. The presence and patterns of ILD were defined by HRCT findings. ROC curve analysis was used to calculate the accuracy of LUS to detect ILD. A total of 120 RA patients (86 women, with a median age of 56.0 [50.0–64.0] years) were enrolled. Based on the HRCT, 76 patients were found to have radiographic ILD, with 63 exhibiting nonspecific interstitial pneumonia (NSIP) and 13 showing usual interstitial pneumonia (UIP). Sonographic ILD was detected in 76 patients who underwent LUS examination. The concordance rate between two modalities was 83.33% (Kappa value = 0.64, 95% CI 0.50–0.78). The diagnostic sensitivity and specificity of LUS were 86.84% and 77.27%, respectively. The positive predictive value, negative predictive value, a positive likelihood ratio and a negative likelihood ratio were 86.84%, 77.27%, 3.82, and 0.17, respectively. The number of B-lines in RA with ILD and without ILD on HRCT showed a significant difference (34.0 [15.0–96.5] vs. 6.5 [2.5–10.0], P < 0.001). The presence of 12 B-lines on 50 ScS was the optimal cutoff value for detecting RA-ILD (AUC = 0.89, 95% CI 0.82–0.94, sensitivity of 85.53%, specificity of 81.82%, P < 0.001). Lung ultrasound is a valuable diagnostic tool for RA-ILD and can be used as a screening method to identify patients who require further evaluation with chest HRCT.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737510","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":"Prevalence, characteristics, and outcomes of patients with low baseline C-reactive protein in giant cell arteritis","authors":"Samuel Pichon, Vincent Koether, Amélie Leurs, Aurelien Chepy, Benoît Gachet, Vincent Sobanski, David Launay, Marc Lambert, Eric Hachulla","doi":"10.1186/s13075-025-03594-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03594-9","url":null,"abstract":"Elevated inflammatory markers play a crucial role in the diagnosis and follow-up of patients with giant cell arteritis (GCA). This study aimed to describe the prevalence, characteristics, and outcomes of patients with low baseline (< 10 mg/L) C-reactive protein (CRP) in GCA. A retrospective observational study was conducted at Lille University Hospital, involving all patients diagnosed with GCA between January 2000 and April 2023. Patients were categorized based on their CRP level at diagnosis. Baseline characteristics, clinical manifestations, laboratory findings, imaging results, and outcomes were compared between patients with baseline CRP < 10 mg/L (“low CRP”) and those with CRP ≥ 10 mg/L (“high CRP”). Of the 380 patients, 7.6% (n = 29) had baseline CRP < 10 mg/L at diagnosis. When compared to the high CRP group, the low CRP group exhibited a lower incidence of fever, and had a higher incidence of ocular involvement, particularly anterior ischemic optic neuropathy (28% vs. 13%, p = 0.04), and limb claudication (24% vs. 8%, p < 0.01). Plasma fibrinogen levels were elevated (> 4 g/L) in 77% of patients with low CRP. Despite differences in clinical presentation, relapse rates were equilibrated between the two groups. GCA patients with low CRP are not rare and present with more ocular and peripheral vascular involvement and less constitutional symptoms in our study. Elevated fibrinogen in these patients suggests active inflammation despite low CRP. Clinicians should consider GCA even with a CRP < 10 mg/L, as these patients may present with severe complications.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"25 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737749","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":"Exploration of bioactive variants of the BMP7-derived p[63–82] peptide for ameliorating the OA-associated chondrocyte phenotype","authors":"Jessica S. J. Steijns, Tim J. M. Welting, Andy Cremers, Guus G. H. van den Akker, Pieter J. Emans, Lodewijk W. van Rhijn, Marjolein M. J. Caron","doi":"10.1186/s13075-025-03599-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03599-4","url":null,"abstract":"Osteoarthritis is a highly prevalent, age-associated joint disease characterized by cartilage degeneration, joint dysfunction, and chronic pain. We previously developed a bone morphogenetic protein 7 derived peptide p[63–82], which may be a novel disease-modifying treatment option for OA. In this study we aimed to optimize the bioactivity and biostability of this peptide in the intra-articular environment to evaluate the therapeutic potential of these peptides to treat osteoarthritis. 33 peptide modifications of p[63–82] were custom-designed and synthesized to optimize the bioactivity. Chondrocytes and synovial fluid were collected from end-stage osteoarthritic patients at total knee arthroplasty surgery. To validate improvements in bioactivity, gene expression analysis, glycosaminoglycan content, matrix metalloproteinase-13 protein levels and alkaline phosphatase activity was measured. Several biochemical approaches were used to explore optimization of the original p[63–82] peptide. One cyclized peptide (C2) was able to significantly increase the expression of collagen type 2 and decrease expression of collagen type 10, matrix metalloproteinase-13 and prostaglandin-endoperoxide synthase 2. The linear p[63–82] peptide and the cyclic peptide variant C2 in the same concentration were effective in suppressing the osteoartritic phenotype in SW1353 cells, despite the presence of interleukin-1β or osteoarthritic-synovial fluid. However, peptide variant C2 had a significantly more favorable bioactivity as compared to p[63–82] in reducing matrix metalloproteinase-13 protein levels in the osteoarthritic-synovial fluid exposed condition. At lower concentrations, the cyclic peptide C2 showed a higher bioactivity as compared to the linear p[63–82] peptide. When the activity of both peptides on primary human articular chondrocytes was evaluated, we found that the linear p[63–82] peptide as well as peptide C2 counteract the hypertrophic and inflammatory state of primary OA chondrocytes. This study demonstrates that among various tested modifications of p[63–82], one cyclic variant (C2) showed similar results in bioactivity as compared to the linear peptide p[63–82], whilst the other modified peptide variants had inactive bioactive properties as compared to the original p[63–82] peptide. This highlights the challenge in enhancing peptide properties without compromising their biological activity and emphasises the need for a cautious approach in peptide modification for therapeutic use. This research underscores that while cyclization and other structural changes may offer benefits, they should be carefully evaluated on a case-by-case basis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"10 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737729","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":"Cytokines, chemokines and antibodies against histone-3/4 citrullinated peptides in rheumatoid arthritis patients with pulmonary fibrosis","authors":"Linda Johansson, Federico Pratesi, Fosca Errante, Lorenzo Pacini, Paola Migliorini, Solbritt Rantapää-Dahlqvist","doi":"10.1186/s13075-025-03603-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03603-x","url":null,"abstract":"Rheumatoid arthritis (RA) associated interstitial lung disease (ILD) is the most common pulmonary manifestations of RA, with a progressive course and a poor survival. An early detection and better treatment is essential to improve outcome. We evaluated 16 analytes that could be relevant for the development of RA ILD. In an inception cohort of 1118 early RA patients, pulmonary fibrosis (PF) were identified in 60 patients after a mean follow-up of 5.3 years using high resolution computer tomography (HRCT). As controls, 124 early RA patients without PF and 94 matched population controls without known rheumatic disease were studied. Analysis of antibodies against histones 3 and 4 derived citrullinated peptides (CitH3/H4), and cytokines/chemokines levels were performed in plasma samples collected at RA diagnosis using in-house ELISA and Luminex analysis. Anti-CitH3(114–135) antibodies were the only antibody with increased frequency and levels in patients with PF versus without PF. The highest OR for PF development were found when combining positivity for anti-CitH3(114–135) and -CitH4(31–50) antibodies, OR 2.26. Levels of IL1α, IL1ß, TNFα, VEGFA and MIPα remained significantly elevated in patients with PF compared without PF, after adjustments and Bonferroni corrections. Several of the cytokines/chemokines correlated significantly with the histone antibodies in patients without PF. Partial least squares discriminant analysis including antibodies against citrullinated histon peptides and cytokines/chemokines identified significantly in PF in non-smokers. Antibodies against CitH3 peptides and several of the analysed cytokines/chemokines in samples collected at diagnosis were associated with subsequent delevopment of PF in patients with RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737750","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":"Lupus nephritis and U1-RNP-antibodies are associated with low bone mineral density and osteoporosis in patients with systemic lupus erythematosus: baseline findings in a sub-cohort of patients with inflammatory rheumatic diseases","authors":"Edgar Wiebe, Elisa Celine Schilling, Dörte Huscher, Andriko Palmowski, Zhivana Boyadzhieva, Sandra Hermann, Burkhard Muche, Mirella Lopez Picazo, Gerhard Krönke, Falk Hiepe, Tobias Alexander, Frank Buttgereit","doi":"10.1186/s13075-025-03610-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03610-y","url":null,"abstract":"Patients with systemic lupus erythematosus (SLE) are at higher risk for osteoporosis and fragility fractures. Our study aimed to identify disease-specific factors with impact on bone mineral density (BMD) and the risk of osteoporosis, and to evaluate the effectiveness of DXA-derived 3D femur parameters versus BMD and trabecular bone score (TBS) in discriminating pre-existent fragility fractures. We analyzed baseline data of a consecutive subcohort of patients with SLE with current or past GC treatment, fulfilling the EULAR/ACR 2019 SLE classification criteria. We used multivariable linear and logistic regression models to identify BMD- and osteoporosis-related factors. DXA-derived 3D measurements of the femur were performed with 3D-Shaper software. Discriminatory performance of BMD, TBS and 3D femoral parameters for fragility fractures was assessed by AUC values. Forty-one percent of 110 patients with SLE had osteoporosis. Lupus nephritis (LN) was present in 35% of cases, with 61% (23/38) of these being predominantly classified as classes IV and V. Factors significantly associated with lower BMD included LN classes III and IV, U1-RNP antibodies, higher C-reactive protein, and longer disease duration. Clinical remission, higher Siglec-1 levels, higher body mass index, and higher health assessment questionnaire (HAQ) scores correlated positively with BMD. Osteoporosis was linked to LN, higher age, HAQ, and complement factor 3 levels. Our findings suggest that 3D bone structure analysis may be helpful in discriminating past vertebral fractures. Disease severity indicated by LN, high CRP, presence of U1-RNP antibodies, and extended disease duration are detrimental to bone health. Moreover, 3D-DXA parameters can be integrated in clinical practise to assess bone health. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"10 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715326","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":"Type II diabetes in systemic sclerosis patients: insights from an observational, multicenter study of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale)","authors":"Vasiliki Liakouli, Giulio Forte, Piero Ruscitti, Luca Navarini, Francesca Bellisai, Francesco Caso, Giuliana Guggino, Lidia La Barbera, Chiara Rizzo, Ada Corrado, Paola Triggianese, Alberto Lo Gullo, Giuseppe Mandraffino, Luca Cantarini, Bruno Frediani, Paola Cipriani, Francesco Paolo Cantatore, Maria Sole Chimenti, Elvira Favoino, Federico Perosa, Annamaria Iagnocco, Roberto Giacomelli, Francesco Ciccia","doi":"10.1186/s13075-025-03619-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03619-3","url":null,"abstract":"To assess the contribution of Systemic sclerosis (SSc)-specific features on type II diabetes mellitus (T2D) in a large cohort of Italian SSc patients. A total of 613 SSc patients from 11 tertiary Rheumatology Units across Italy were included. All patients underwent full history taking, clinical examination, and relevant laboratory and radiological evaluations. Demographic, socioeconomic, and disease-specific factors were compared between SSc patients with and without T2D. The prevalence of T2D in the study cohort was 7.6%. SSc patients with T2D were significantly older (P < 0.007) and exhibited: higher prevalence of late-stage capillaroscopic pattern (P < 0.001), severe reduction in forced vital capacity (FVC < 50%; P < 0.000), moderate reduction in total lung capacity (TLC 50–69%; P < 0.011), electrocardiographic signs of right ventricular hypertrophy (P < 0.018), higher prevalence of pulmonary arterial hypertension (PAH) confirmed by right heart catheterization (RHC) (P < 0.037) and higher prevalence scleroderma renal crisis (SRC) (P < 0.001); elevated erythrocyte sedimentation rate (ESR) (P < 0.022), and ANA positivity. These patients more frequently assumed angiotensin-converting enzyme inhibitors (ACEi) (P < 0.005) when compared to their non-T2D counterparts, while the use of immunosuppressive therapies was similar between groups. Multivariate analysis identified older age, SRC, and reductions in both TLC and FVC as independent SSc-specific associated factors of T2D. Although the prevalence of T2D in SSc patients is lower than the global estimates reported by the International Federation of Diabetes (IFD), a distinct subgroup of SSc patients with T2D is characterized by unique disease manifestations and complications, including SRC and impaired lung function. These findings underscore the importance of tailored screening and management approaches to address the intersecting metabolic and vascular risks in this population.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"56 12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715327","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}