Clinical Rheumatology最新文献

{"title":"Exploring the molecular mechanism of Tripterygium Wilfordii Hook F in treating systemic lupus erythematosus via network pharmacology and molecular docking.","authors":"Yanggang Hong, Deqi Wang, Hengrong Qian, Xiaoyang Jiang, Yi Wang, Xinyue Liang, Sheng Gao, Chunyan Hua","doi":"10.1007/s10067-025-07311-4","DOIUrl":"https://doi.org/10.1007/s10067-025-07311-4","url":null,"abstract":"<p><strong>Background: </strong>Tripterygium wilfordii Hook F (TwHF) is a prominent Chinese herbal formula. It exhibits significant clinical efficacy in treating systemic lupus erythematosus (SLE), though its mechanisms remain unclear. Our study employs network pharmacology and molecular docking to explore active compounds of TwHF and their associated targets for SLE treatment.</p><p><strong>Methods: </strong>Primary active compounds of TwHF and their targets were sourced from the TCMSP, SwissTargetPrediction, and UniProt databases. SLE-relevant target proteins were identified from the OMIM and GeneCards databases. Enrichment analyses were conducted to reveal results of common TwHF-SLE targets. STRING and Cytoscape software were used to systematically analyze and construct protein-protein interaction (PPI) networks, compound-target-pathway, and target-organ networks. Molecular docking was utilized to confirm the binding of key targets to the top active compounds.</p><p><strong>Results: </strong>A total of 14 active compounds and 300 overlapping targets between TwHF and SLE were identified. PPI network analysis revealed 29 core targets. Several pathways were found to contribute to the potential therapeutic effects of TwHF in SLE, including PI3K-Akt signaling pathway, Th17 cell differentiation, chemokine signaling, and T cell receptor signaling. Disease Ontology (DO) analysis highlighted the involvement of TwHF in genes associated with myocardial infarction (MI), atherosclerosis (AS), breast carcinoma, and ischemia. Molecular docking results demonstrated strong binding affinities, with 37 signal molecule-receptor interactions in SLE and 97 interactions in SLE-related MI and AS showing binding energies lower than -7 kJ/mol.</p><p><strong>Conclusions: </strong>This research effectively anticipates the potent constituents, probable targets, and pathways implicated in treating SLE with TwHF, specifically addressing complications such as MI and AS. Comprehending the precise molecular mechanism targeting SLE of TwHF and its efficacious bioactive components furnishes a theoretical groundwork for enhancing its clinical utilization. Key Points •SLE is characterized by aberrant immune activation and persistent inflammation. •TwHF exerts immunomodulatory and anti-inflammatory effects. •TwHF exhibits prospects in the treatment of SLE with unknown molecular mechanisms. •Network pharmacology and molecular docking reveal promise in the mechanism of TwHF.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating treatment responsiveness in rheumatoid arthritis through predictive metabolomic profiling: A systematic review of studies examining methotrexate, TNF, and IL-6 inhibitors as therapeutic interventions.","authors":"Larisa M Musaeva, Ksenia M Shestakova, Sabina N Baskhanova, Valeria G Varzieva, Alex Brito, Irina Menshikova, Svetlana A Appolonova","doi":"10.1007/s10067-025-07355-6","DOIUrl":"https://doi.org/10.1007/s10067-025-07355-6","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease characterized by joint damage and systemic involvement. Despite advancements in understanding RA, early diagnosis and effective treatment remain challenging due to the complex pathogenesis and limited specificity of current biomarkers. Metabolomics, offers a promising approach for identifying new biomarkers to assess treatment responsiveness in RA. A systematic review was conducted to identify key metabolites and metabolic pathways that may reveal responsiveness to different drug therapy strategies (methotrexate, TNF, and IL-6 inhibitors) in RA treatment. The systematic search was conducted in PubMed and Google Scholar in accordance with PRISMA recommendations. The risk of bias and the quality of the final selected studies were assessed in duplicate using the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool and using the QUADOMICS tool. Eighteen studies were eligible for data extraction. Metabolomic studies revealed distinct profiles for responders and non-responders to different RA treatments. For methotrexate therapy, key metabolites included for example: homocysteine, glycerol-3-phosphate, and diphosphoglyceric acid. TNF inhibitor response was associated mainly with changes in carbohydrate derivatives and amino acids. IL-6 inhibitor studies identified metabolites such as N-acetylglucosamine, N-acetylgalactosamine, and N-acetylneuraminic acid as potential predictors of response. Across studies, metabolomic profiles demonstrated high sensitivity and specificity in distinguishing responders from non-responders. These studies collectively highlight alterations in TCA cycle metabolites, amino acids, nucleotide metabolism, and lipid profiles, among others. This review supports the identification of better treatment strategies choosing methotrexate, TNF, or IL-6 inhibitors as therapeutic interventions based on metabolomics profiling.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early axial spondyloarthritis versus established disease: a single-center analysis based on the new ASAS definition of early disease.","authors":"Sara Alonso, Paula Alvarez, Norma Calleja, Rubén Queiro","doi":"10.1007/s10067-025-07365-4","DOIUrl":"https://doi.org/10.1007/s10067-025-07365-4","url":null,"abstract":"<p><strong>Objectives: </strong>The applicability of the new Assessment of Spondyloarthritis International Society (ASAS) consensus definition of early axial spondyloarthritis (axSpA) has barely been tested in clinical settings. We aimed to check the applicability of this new definition in a real clinical context.</p><p><strong>Methods: </strong>Single-center cross-sectional study involving 330 consecutive patients fulfilling axSpA criteria. Similarities and differences between patients with early (according to the new ad hoc definition) and established disease were analyzed. Logistic regression models adjusted for sex and exposure to biologic therapies were constructed to analyze the different disease outcomes between both subpopulations.</p><p><strong>Results: </strong>Of 299 patients for whom information on defining characteristics of early axSpA could be reliably collated, 45 (15%) met the ASAS definition of early axSpA, median disease duration of 1.0 year [IQR, 1.0-2.0]. Compared to established disease, these patients were younger (p = 0.001), with a similar male-to-female ratio, and a higher exposure to NSAIDs (p = 0.015) but lower to biologics (p = 0.005). Uveitis prevalence was similar between both groups (early, 15.6% and established, 16.1%). Regardless of sex and biologic therapy, inflammatory burden, disease activity and the impact on quality of life were similar in both groups. As expected, structural damage was higher among established cases. Also, regardless of disease duration and exposure to biologic therapies, men had better disease outcomes than women.</p><p><strong>Conclusion: </strong>Patients with early axSpA present similarities and differences with respect to established cases. The new ASAS definition of early disease may be applicable in real-world clinical settings.</p><p><strong>Key points: </strong>• Patients with early axial spondyloarthritis show similarities and differences with respect to established cases. • The overall burden of disease is similar in both subgroups of patients with axial SpA. • In both study groups, men showed better disease outcomes than women. • The new ASAS definition of early axial spondyloarthritis is applicable in real-life clinical settings.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a prediction model for serious infections in rheumatoid arthritis patients treated with tocilizumab in Japan.","authors":"Toshihiro Nanki, Tomohiro Yamaguchi, Kosei Umetsu, Ryunosuke Tanabe, Naoki Maeda, Minori Kanazawa, Yuko Furuno, Shinichi Matsuda, Shinya Takemoto, Keiko Asao, Tatsuya Kamiuchi","doi":"10.1007/s10067-025-07328-9","DOIUrl":"https://doi.org/10.1007/s10067-025-07328-9","url":null,"abstract":"<p><strong>Objectives: </strong>To develop a prediction model for serious infections (SIs) in rheumatoid arthritis (RA) patients treated with tocilizumab in Japan and to evaluate the model's performance compared to previously developed models, i.e., 'DANBIO' and 'postmarketing surveillance' (PMS).</p><p><strong>Method: </strong>This non-interventional retrospective cohort study utilized the Medical Data Vision database in Japan. The study population was derived from patients ≥ 18 years with RA who initiated tocilizumab between April 2008 and July 2021. SIs were assessed during the 1-year follow-up from tocilizumab initiation. The candidate predictors were identified based on previous studies, known risk factors, potentially relevant factors, and data availability. The prediction model was developed using logistic regression. The model's performance was compared with previously developed models using cross-entropy and area under the receiver operating characteristic curve (AUC).</p><p><strong>Results: </strong>Of the 6501 RA patients, 4.57% experienced SIs during the 1-year follow-up. The model included 17 predictors for SI (e.g., age (odds ratio 1.013 (95% confidence interval 1.002-1.024)), history of SIs (2.569 (1.636-3.745)), diverticulitis (2.183 (1.000-3.989))). The model showed a lower cross-entropy and a higher AUC (0.1488; 0.712) compared to DANBIO (0.1932; 0.591) and PMS (0.1561; 0.565) models, and the sensitivity, specificity, positive predictive value, and negative predictive value using 5% threshold were 72%, 64%, 7%, and 98%, respectively.</p><p><strong>Conclusions: </strong>The model developed in this study seems to have the potential to inform the risk of SIs in RA patients treated with tocilizumab and may help the early identification of patients at risk of SIs to reduce morbidity and mortality.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediating effect of X-26109 on the causal relationship between CD14⁺ CD16^- monocyte activation complex and rheumatoid arthritis in Europe.","authors":"Han Wang, Jinjie Chu, Yan Wang, Yongqin Wu, Wenchao Zhou","doi":"10.1007/s10067-025-07300-7","DOIUrl":"https://doi.org/10.1007/s10067-025-07300-7","url":null,"abstract":"<p><p>The regulation of the immune system is crucial in the pathogenesis of various diseases. The direct involvement of immune cells in the development of rheumatoid arthritis (RA) and the potential mediation by metabolites remains to be elucidated. This study utilized a two-step, two-sample Mendelian randomization (MR) approach employing the inverse variance weighted (IVW) method to investigate the causal role of immune cells in RA and to assess the mediation effect of metabolites on the association between immune cells and RA. MR analyses identified 44 immune cell traits that were suggestively associated with RA. Additionally, five metabolites demonstrated protective effects against RA. Notably, mediation MR indicated that the causal role of CD14⁺ CD16^- monocyte activation complex (AC) on RA (total effect IVW: OR = 0.978, 95% CI [0.959, 0.998], P = 0.028) was significantly mediated by X-26109 levels, accounting for 7.32% of the total effect. This study provides evidence of a causal relationship between immune cells and RA, with metabolites potentially mediating this relationship. Key Points • Mendelian randomization (MR) analysis was used to investigate the causal impact of immune cells on RA progression and the potential mediating role of metabolites, identifying 44 immune cell traits and several metabolites associated with RA risk • The study found that CD14 + CD16 - monocyte activation complex (AC) is associated with a reduced RA risk, with this effect largely mediated by metabolite X-26109 levels, suggesting a potential therapeutic target for RA prevention and treatment.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with nintedanib is as effective and safe in patients with other connective tissue diseases (CTDs)-interstitial lung disease (ILD) as in patients with systemic sclerosis-ILD: A multicenter retrospective study.","authors":"Salim Mısırcı, Ali Ekin, Burcu Yağız, Belkıs Nihan Coşkun, Fatma Başıbüyük, Ahmet Merih Birlik, İsmail Sarı, Aylin Dolu Karaca, Süleyman Serdar Koca, Gözde Yıldırım Çetin, Burak Okyar, Nurhan Atilla, Ediz Dalkılıç, Yavuz Pehlivan","doi":"10.1007/s10067-025-07323-0","DOIUrl":"https://doi.org/10.1007/s10067-025-07323-0","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to assess the efficacy and safety of nintedanib (NTD) therapy in a real world population of patients with connective tissue diseases related interstitial lung disease (CTDs-ILD).</p><p><strong>Methods: </strong>Our multicenter retrospective study included patients with a CTD-ILD diagnosis who started NTD treatment due to the development of PPF during follow-up. The results of the percentage predicted forced vital capacity (%pFVC) and percentage predicted diffusion capacity (%pDLCO) of patients before NTD treatment and 6, 12 and 18 months after the start of NTD treatment were evaluated. In addition, the patients were divided into two groups, SSc-ILD and other CTDs-ILD, and compared in terms of the efficacy and safety of the NTD.</p><p><strong>Results: </strong>In all patients (n = 66), %pFVC and %pDLCO values stabilised after 6, 12 and 18 months compared to baseline values. All patients received at least one immunosuppressive therapy in combination with NTD treatment. The most common side effect after NTD treatment was diarrhoea (n = 20, 30.3%). When we divided the patients into two groups, SSc-ILD (n = 35) and other CTDs-ILDs (n = 31), no significant difference was found between the groups in the change in %pFVC (p values = 0.498, 0.595 and 0.376, respectively) and in the change in %pDLCO (p values = 0.817, 0.185 and 0.399, respectively) at 6, 12 and 18 months follow-up. Again, there was no statistically significant difference between the two groups in terms of adverse events and safety data after NTD treatment (p > 0.05).</p><p><strong>Conclusion: </strong>In summary, the use of NTD in combination with immunosuppressive therapies was effective and safe in SSc-ILD patients as well as in other CTDs-ILD patients. Key Points • This multicenter study provides real-world data on the use of nintedanib in patients with connective tissue disease-interstitial lung disease. • Nintedanib treatment is as effective and safe in patients with other connective tissue disease as in patients with systemic sclerosis.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the causal relationship between rheumatoid arthritis and cardiovascular disease: A Mendelian randomization study.","authors":"Xintong Xie, Guangliang Wei, Zhenboyang Tang, Huidong Chen, Xiru Lin, Chunyan Huang, Hao Yu, Youxian He, Mengxiang Li, Xue Zhang, Chengsong He, Yue He, Jie Chen","doi":"10.1007/s10067-025-07357-4","DOIUrl":"https://doi.org/10.1007/s10067-025-07357-4","url":null,"abstract":"<p><strong>Objective: </strong>Previous research has revealed a positive correlation between rheumatoid arthritis (RA) and cardiovascular diseases, but the causal relationship is unclear. This study applies Mendelian randomization to examine whether RA causally contributes to the likelihood of various cardiovascular diseases, such as heart failure, coronary artery disease, and atrial fibrillation.</p><p><strong>Methods: </strong>Using genome-wide association data, we conducted a univariable MR (UVMR) analysis to evaluate the causal impact of RA on CVD, primarily utilizing the inverse variance weighted method. Additional MR methods were used to test the robustness of the results. Multivariable MR (MVMR) was applied to explore potential confounders.</p><p><strong>Results: </strong>In the European population, genetically predicted RA had a harmful causal effect on HF, with the IVW analysis indicating an OR of 1.06 (95% CI: 1.02-1.10, P < 0.01) based on 23 SNPs. No causal relationships were found between RA and other CVDs. The MVMR analysis did not identify significant causal impact of rheumatoid arthritis on HF after controlling for traditional risk factors. In the Asian population, RA was associated with an adverse effect on AF, with the IVW method reporting an OR of 1.20 (95% CI: 1.01-1.41, P = 0.03) for 5 SNPs. No other CVD relationships were found.</p><p><strong>Conclusions: </strong>Our MR analysis indicates that genetic susceptibility to rheumatoid arthritis increases the likelihood of heart failure in European populations and atrial fibrillation in East Asian populations. However, established CVD risk factors, such as smoking, overweight, and physical inactivity, remain critically important in the management of RA. Key Points • Multiple studies have highlighted a marked increase in the cardiovascular event risk among individuals with RA. However, additional RCTs are needed for confirmation. • We applied Mendelian randomization to explore the potential causal relationship between rheumatoid arthritis and cardiovascular conditions. The findings demonstrated a causal link between RA and heart failure among European populations, as well as an association between RA and atrial fibrillation in East Asian groups. • Further adjustments using multivariable Mendelian randomization to account for the influence of traditional cardiovascular risk factors revealed that the causal association between RA and heart failure disappeared.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low prevalence of methotrexate intolerance in rheumatoid arthritis: a South African study.","authors":"Namuhla Qwabe, Farhanah Paruk, Girish Mahasukhlal Mody","doi":"10.1007/s10067-025-07310-5","DOIUrl":"https://doi.org/10.1007/s10067-025-07310-5","url":null,"abstract":"<p><strong>Introduction: </strong>Methotrexate (MTX) is the first line therapy for rheumatoid arthritis (RA), and despite its widespread use, there is very little information about MTX intolerance in sub-Saharan Africa. The aim of this study was to assess the prevalence of MTX intolerance and other reasons for stopping MTX in RA in South Africa.</p><p><strong>Methods: </strong>A retrospective chart review of all RA patients seen at Inkosi Albert Luthuli Hospital in Durban from 2009 to 2019 was undertaken. We included patients who received MTX for at least three months. All patients received folic acid supplements. Patients who discontinued MTX were categorized as having either MTX related toxicity or other reasons.</p><p><strong>Results: </strong>A total of 695 patients were identified with a female to male ratio of 7:1. The mean age was 57.9 (± 13.3) years, and median duration of MTX use was 67.0 (39.0-106.0) months. Most of the patients were African Blacks (61.2%), and Indians (32.8%). There were 83 (11.9%) patients who stopped MTX, and it was successfully reintroduced in 25 of them. Thus, 58 (8.3%) patients discontinued therapy, 33 (4.7%) due to intolerance and 25 (3.6%) due to factors other than adverse effects. The commonest causes of MTX intolerance were respiratory, gastrointestinal and haematological. The other reasons for discontinuation included co-morbidities and pregnancy related concerns.</p><p><strong>Conclusions: </strong>The low prevalence of MTX intolerance in a multiethnic population in this single centre study, confirms the value of MTX as anchor therapy, especially in resource constrained settings. Key Points • We report a low and similar prevalence of methotrexate intolerance in a large population of African Blacks and Indians with RA in sub-Saharan Africa. • Even though there was heterogeneity among other studies, our review indicates that MTX was tolerated better in our patients compared to patients in Europe and the United States of America.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International overview on juvenile-, adult- and elderly-onset rheumatoid arthritis: The age at disease onset as a fundamental determinant of clinical presentation.","authors":"Nevin Hammam, Tahsin El-Hadidi, Khaled El-Hadidi, Ahmed Elsaman, Samah A El-Bakry, Maha Nassr, Hanan M El-Saadany, Doaa Mosad, Samah I Nasef, Zahraa I Selim, Nermeen Samy, Abdelhfeez Moshrif, Hanan Taha, Rasha M Fawzy, Suzan S Al-Adle, Amira M Ibrahim, Nora Y Elsaid, Samar Tharwat, Nada M Gamal, Maha E Ibrahim, Soha Senara, Rawhya El Shereef, Marwa A Amer, Faten Ismail, Mervat I Abd Elazeem, Nouran M Abaza, Eman F Mohamed, Dina F El-Essawi, Saad M Elzokm, Samar M Fawzy, Nahla N Eesa, Enas A Abdelaleem, Ahmed M Abdalla, Hanan M Fathi, Hatem H El-Eishi, Safaa Sayed, Reem Hamdy A Mohammed, Tamer A Gheita","doi":"10.1007/s10067-025-07356-5","DOIUrl":"https://doi.org/10.1007/s10067-025-07356-5","url":null,"abstract":"<p><strong>Background: </strong>Elderly-onset rheumatoid arthritis (EORA) may have peculiar findings compared to juvenile-onset RA (JORA). The aim of the work was to present and compare the clinical characteristics of RA patients with JORA and elderly-onset EORA to a group of cases with adult-onset (AORA) and to contrast the findings worldwide.</p><p><strong>Methods: </strong>The study included 1100 adult RA patients: 209 JORA and 329 EORA, compared with 562 AORA extracted from a big data national study on 10,364 RA patients. Clinical characteristics, laboratory investigations, medications received, and co-morbidities were recorded. The disease activity index (DAS28) and health assessment questionnaire (HAQ) were estimated.</p><p><strong>Results: </strong>The JORA cases represented 19% and EORA 29.9% of the included cohort. The mean age at onset for JORA, EORA, and AORA were 15.1 ± 2.1, 64 ± 4.2, and 36.4 ± 10 years (p < 0.0001), and the female-male ratio was 6.2:1, 2.7:1, and 7.3:1 (p < 0.0001), respectively. In EORA, body mass index (28.8 ± 5.8) and frequencies of smokers (11.6%), diabetes (12.2%), hypertension (19.8%), and osteoporosis (5.2%) were significantly higher than in JORA (26.02 ± 5; 5.3%, 2.9%, 3.8%, and 1%) and AORA (27.6 ± 5.6; 3%, 8.4%, 14.9%, and 2.3%, p = 0.016) (p < 0.0001, p = 0.001, p < 0.0001, and p = 0.009, respectively). In JORA, oral ulcers were significantly more frequent (p = 0.04); in EORA, cardiovascular manifestations (p < 0.0001) and hypothyroidism (p = 0.039) were more frequent; and DAS28 (p = 0.01) and HAQ (p = 0.038) were higher. Fibromyalgia and methotrexate administration were significantly more frequent in AORA (p < 0.0001 and p = 0.04, respectively). Rheumatoid factor, anti-cyclic citrullinated peptide, and double seropositivity were significantly more frequent in EORA (p < 0.0001, p = 0.008, and p = 0.002, respectively).</p><p><strong>Conclusion: </strong>Comorbidities, cardiovascular manifestations, hypothyroidism, higher disease activity, and functional disability are more common in EORA patients. Key Points • Juvenile-onset and elderly-onset RA patients have notable differences compared to the adult-onset cases. • Co-morbidities and certain manifestations, including cardiovascular disease and hypothyroidism, as well as higher disease activity and functional disability, are more common in elderly-onset patients. • Fibromyalgia remains more frequent in adult-onset cases.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of Catalpol to attenuate TNF- α and collagen-induced inflammation in vitro HFLS-RA cells and in vivo mice models for the treatment of rheumatoid arthritis.","authors":"Bin Wu, Qinyan Dong, Qin Zhang, Fangqin Jin, Jiangping Weng","doi":"10.1007/s10067-024-07261-3","DOIUrl":"https://doi.org/10.1007/s10067-024-07261-3","url":null,"abstract":"<p><strong>Background/rationale: </strong>Rheumatoid Arthritis (RA) is a prolonged autoimmune condition marked by persistent inflammation, causing joint damage and bone erosion. Catalpol (CAT), an iridoid glycoside, offers anti-inflammatory benefits, warranting its study in RA models.</p><p><strong>Objective: </strong>To investigate the anti-inflammatory effects of CAT in RA by evaluating its impact on cellular and animal RA models.</p><p><strong>Methods: </strong>In vitro biological actions of CAT were investigated by the methods of cell viability, proliferation, migration, invasion, apoptosis, ROS generation, double luciferase reporter assay for NF-κB-p65 activity, Nitrite release detection, and RT-qPCR for gene expression in Tumor Necrosis Factor-alpha (TNF-α)-induced Human Fibroblast-Like Synoviocytes from RA patients (HFLS-RA) (cellular RA model). Arthritis severity, joint cellular structure, gene expression, inflammatory factors, and joint inflammation studies were investigated in mice with collagen-induced arthritis (CIA) (animal RA model).</p><p><strong>Key results: </strong>CAT treatment groups showed significant improvements (P < 0.001) in cell viability, migration, invasion, and apoptosis compared to the TNF-α-induced group. ROS generation and the activity of NF-κB-p65 were significantly reduced (P < 0.001). Nitrite release was decreased (P < 0.01, P < 0.001) in CAT-treatment groups. Pro-inflammatory and bone-metabolizing cytokine gene expression was markedly downregulated (P < 0.05, P < 0.001) in the cellular RA model. CIA mice treated with CAT exhibited significantly reduced arthritis severity, paw edema, and arthritis index (P < 0.05, P < 0.01). Joint pathology scores showed improvement (P < 0.001) in CAT-treatment groups. In the animal RA model, bone-metabolizing and inflammatory cytokine gene expression was significantly reduced in CAT-treatment groups (P < 0.01, P < 0.001).</p><p><strong>Conclusion: </strong>CAT effectively reduces RA's inflammation and bone metabolism issues, suggesting its potential as a therapeutic agent for RA treatments. Key Points • Plant-derived Catalpol compound is an effective choice for rheumatoid arthritis treatment due to its anti-inflammatory potential. • CAT's effects were tested on TNF-α-induced HFLS-RA cells and in CIA mice, assessing cell viability, apoptosis, ROS generation, arthritis severity, inflammatory factors, and joint inflammation studies. • The administration of CAT could greatly enhance cell health and reduce inflammation markers and arthritis symptoms. • Observed significant reduction of RA inflammation and bone issues, confirming CAT as a therapeutic agent in RA treatment.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}