{"title":"Rheumatoid arthritis: emerging insights into molecular mechanisms and targeted immunotherapy.","authors":"Weiming Yang, Juanjuan Chen, Xiaozhong Wang","doi":"10.55563/clinexprheumatol/dgbqaa","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/dgbqaa","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disease that characterised by persistent synovial joints inflammation, which ultimately results in progressive joint destruction and significant disability. Ineffective drug treatment for severe arthritis can lead to significant physical disability and a marked decline in quality of life. Recent research has significantly advanced our understanding of the underlying molecular mechanisms of RA, which leads to the emergence of novel immunotherapeutic strategies that provide patients with a broader range of treatment options. This review aims to synthesise the current knowledge of the molecular mechanisms of RA, related signalling pathways, and the latest immunotherapy approaches, including biologic agents, targeted small molecules, and novel therapies.Furthermore, we will discuss the efficacy and safety profiles of these therapies, analyse pressing issues in contemporary research, and explore future directions in the field.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisa Bellis, Mariele Gatto, Gloria Crepaldi, Valeria Data, Claudia Lomater, Elena M Marucco, Silvia Perrone, Marta Saracco, Annamaria Iagnocco
{"title":"Retention rate and predictors of discontinuation for secukinumab treatment: real-life data in a cohort of patients with spondyloarthritis.","authors":"Elisa Bellis, Mariele Gatto, Gloria Crepaldi, Valeria Data, Claudia Lomater, Elena M Marucco, Silvia Perrone, Marta Saracco, Annamaria Iagnocco","doi":"10.55563/clinexprheumatol/cruuvo","DOIUrl":"10.55563/clinexprheumatol/cruuvo","url":null,"abstract":"<p><strong>Objectives: </strong>This study evaluated the real-world retention rate and predictors of discontinuation for secukinumab therapy in patients with spondyloarthritis (SpA).</p><p><strong>Methods: </strong>This observational, retrospective cohort study included SpA patients treated with secukinumab at a referral centre. Baseline demographic and clinical data were recorded, covering comorbidities, prior biologic/targeted synthetic therapies, and disease duration. Secukinumab retention rates were analysed at 12 months and at the end of the study (last observation or discontinuation). Drug retention rate (DRR) was assessed using time-to-discontinuation, with log-rank testing for comparisons. Cox proportional hazards regression models identified baseline predictors of discontinuation.</p><p><strong>Results: </strong>A total of 178 patients (64.6% female) were included. The overall DRR for secukinumab was 64%, with the highest retention rate of 78% at 1 year. Discontinuation reasons included secondary inefficacy (57.8%), primary inefficacy (25%), and adverse events (17.2%), with infections being the most common adverse event. Higher body mass index (BMI) (HR 1.07, 95% CI: 1.02-1.12, p=0.010) and previous treatments (HR 1.34, 95% CI: 1.03-1.73, p=0.030) predicted long-term discontinuation. For 12-month discontinuation, peripheral phenotype (HR 4.28, 95% CI: 1.26-14.48, p=0.019) and prior biologic/targeted synthetic therapies (HR 1.76, 95% CI: 1.24-2.51, p=0.002) were predictors, while axial involvement was protective (HR 0.37, 95% CI: 0.17-0.83, p=0.016).</p><p><strong>Conclusions: </strong>Secukinumab demonstrates sustained effectiveness in SpA patients, with a significant proportion maintaining therapy over time. Retention is influenced by BMI, prior treatments, and disease phenotype, suggesting that outcomes may be optimised through tailored patient selection and early intervention.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1561-1567"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alojzija Hočevar, Aleš Grošelj, Gregor Hawlina, Matic Koželj, Andrej Škoberne, Jože Pižem, Vesna Jurčić
{"title":"The performance of histological criteria for IgG4-related disease in clinical practice.","authors":"Alojzija Hočevar, Aleš Grošelj, Gregor Hawlina, Matic Koželj, Andrej Škoberne, Jože Pižem, Vesna Jurčić","doi":"10.55563/clinexprheumatol/peqyb4","DOIUrl":"10.55563/clinexprheumatol/peqyb4","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1696-1697"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pathogenesis of rheumatoid arthritis: one year in review 2025.","authors":"Giulia Noto, Francesca Salvetti, Adriana Demaj, Piera Altieri, Erica Chericoni, Elisa Ferrigno, Alessia Alunno, Ilaria Puxeddu","doi":"10.55563/clinexprheumatol/53rkan","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/53rkan","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterised by joint destruction and extra-articular manifestations. A close interaction between both innate and adaptive immune systems leads to the development of the clinical features of the disease, characterised by inflammation and structural changes. Progress in the basic and clinical research in the field of RA has improved the current knowledge on the mechanisms underlying its pathogenesis. The data obtained from basic and clinical studies in RA has actively contributed to identifying new potential targets for novel therapeutic approaches to design personalised therapy of the disease.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":"43 9","pages":"1533-1540"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yong-Long Yan, Ya-Shuang Su, Jing-Jing Cao, Jie Lin, Jun-Lie Sun, Cui-Fang Zhang, Rui-De Su
{"title":"Research trends of the aetiology of systemic lupus erythematosus in the past 10 years: a bibliometric analysis (2014-2023).","authors":"Yong-Long Yan, Ya-Shuang Su, Jing-Jing Cao, Jie Lin, Jun-Lie Sun, Cui-Fang Zhang, Rui-De Su","doi":"10.55563/clinexprheumatol/yvqg5k","DOIUrl":"10.55563/clinexprheumatol/yvqg5k","url":null,"abstract":"<p><strong>Objectives: </strong>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by a complex aetiology that encompasses genetic, environmental, and immunological factors. A comprehensive understanding of SLE aetiology is essential for the development of effective therapeutic strategies and the enhancement of patient outcomes. This study aims to provide a thorough bibliometric analysis of research concerning the aetiology of SLE conducted over the past decade.</p><p><strong>Methods: </strong>A bibliometric analysis was conducted based on articles published between January 2014 and December 2023, retrieved from the Web of Science Core Collection database. The analysis employed the R package 'bibliometrix', as well as VOSviewer and CiteSpace.</p><p><strong>Results: </strong>A total of 5,825 publications were analysed. The results underscore the global collaborative nature of SLE research, with significant contributions from China, the USA, and Japan. Notable institutions included Harvard University, the Chinese Academy of Medical Sciences, and the Egyptian Knowledge Bank. Influential journals in the field comprised Arthritis & Rheumatology, Annals of the Rheumatic Diseases, and Frontiers in Immunology. Key word analysis revealed a recent emphasis on terms such as 'management','efficacy', and 'safety', together with emerging interests in 'health' and 'genes'.</p><p><strong>Conclusions: </strong>This study provides a bibliometric analysis of SLE aetiology research, highlighting evolving research trends, influential studies, and collaborative networks. The findings indicate a shift in research focus from specific disease pathogenesis and expression toward genetic mechanisms, diagnostic approaches, and clinical applications. Future research on SLE aetiology is likely to prioritise investigations into DNA, genes, and validating existing findings.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1650-1660"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiujiao Wang, Jian Tang, Fengyun Lu, Xue Zhang, Juan Yao, Ping Gu, Mei Sun, Yanyan Wang
{"title":"A novel nomogram based on the identification of sTREM2 as a biomarker to predict developing neuropsychiatric systemic lupus erythematosus in lupus patients.","authors":"Xiujiao Wang, Jian Tang, Fengyun Lu, Xue Zhang, Juan Yao, Ping Gu, Mei Sun, Yanyan Wang","doi":"10.55563/clinexprheumatol/1tcgmj","DOIUrl":"10.55563/clinexprheumatol/1tcgmj","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify potential biomarkers and construct a nomogram able to predict the development of neuropsychiatric systemic lupus erythematosus (NPSLE) among SLE patients.</p><p><strong>Methods: </strong>Using bioinformatics analysis, TREM2 was identified as an upregulated gene in NPSLE, participating in various pathological pathways of NPSLE. This study included 80 NPSLE patients and three matched SLE controls with no neuropsychiatric events (non-NPSLE controls) for each of the NPSLE patients. Both serum and cerebrospinal fluid (CSF) concentrations of soluble TREM2 (sTREM2) were assessed. The diagnostic capability of sTREM2 for NPSLE was evaluated using the receiver-operating characteristic curve (ROC curves). The study subsequently integrated a substantial volume of clinical data. Following missing data imputation, patients were randomly allocated to either the training set or the validation set. The Boruta algorithm and Multiple analyses were utilized for constructing the nomogram. Diagnostic performance was assessed using ROC curves, the Hosmer-Lemeshow test, and clinical decision curves.</p><p><strong>Results: </strong>sTREM2 levels were notably elevated in both serum and CSF of NPSLE patients compared to non-NPSLE controls. Serum TREM2 concentrations correlated with NPSLE severity and neuropsychiatric state. Notably, higher SLE Disease Activity Index (SLEDAI), increased systemic lupus international collaborating clinics (SLICC)/ACR damage index (SDI), prolonged activated partial thromboplastin time (APTT), a higher serum B cells, and elevated serum sTREM2 levels emerged as significant predictors for NPSLE.</p><p><strong>Conclusions: </strong>sTREM2 presents as a promising biomarker for NPSLE diagnosis. The nomogram that includes serum sTREM2 level as one of the predictors is effective for distinguishing NPSLE from non-NPSLE patients.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1582-1592"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesca Buzzulini, Danilo Villalta, Giulia Previtali, Maria Grazia Alessio, Giacomo Cafaro, Elena Bartoloni, Roberto Gerli, Nicola Bizzaro
{"title":"Diagnostic performance of particle-based multi-analyte technology compared to indirect immunofluorescence in screening for anti-nuclear antibodies in patients with autoimmune rheumatic diseases.","authors":"Francesca Buzzulini, Danilo Villalta, Giulia Previtali, Maria Grazia Alessio, Giacomo Cafaro, Elena Bartoloni, Roberto Gerli, Nicola Bizzaro","doi":"10.55563/clinexprheumatol/h03g16","DOIUrl":"10.55563/clinexprheumatol/h03g16","url":null,"abstract":"<p><strong>Objectives: </strong>In autoimmune rheumatic disease (ARD), ANA testing is crucial for orienting clinical diagnosis and further diagnostic workups. We evaluated the performance of a fully automated system using particle-based multi-analyte technology (PMAT) and compared it to indirect immunofluorescence (IIF) on HEp-2 cells.</p><p><strong>Methods: </strong>Serum samples from 1241 subjects were collected in 13 Italian rheumatology centres. The ARD group (782 samples) included 164 patients affected by systemic lupus erythematosus, 277 by Sjögren's syndrome, 132 by systemic sclerosis, 106 by idiopathic inflammatory myopathy, and 103 by undifferentiated connective tissue disease. The control group comprised 120 healthy donors, 221 patients affected by other autoimmune/inflammatory disorders, and 118 patients affected by acute or chronic infections.</p><p><strong>Results: </strong>In the overall ARD population, HEp-2 IIF showed higher sensitivity when compared to Aptiva/PMAT (92.8 vs. 82.6%) except in the case of idiopathic inflammatory myopathy (58.5% vs. 82.1%). Conversely, Aptiva/PMAT showed higher specificity (77.9% vs. 54.0%) and a higher likelihood ratio for positive results (3.81 vs. 2.08). Double-positive samples provided an LR for positive results higher than one method alone (6.31).</p><p><strong>Conclusions: </strong>This is the first study comparing Aptiva/PMAT against HEp-2 IIF in ANA detection. While the diagnostic sensitivity of this novel method is lower than that of HEp-2 IIF, its high specificity is a valuable tool in the diagnosis of patients affected by ARD and improves their stratification into specific disease subsets. The combined use of HEp-2 IIF and Aptiva/PMAT assays increases diagnostic accuracy and significantly enhances the potential to accurately classify patients affected by ARDs.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1622-1628"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reduction of non-classical monocytes that suppress interferon-α in patients with systemic lupus erythematosus.","authors":"Akina Ishii, Shingo Nakayamada, Naoaki Ohkubo, Yusuke Miyazaki, Shigeru Iwata, Junpei Annan, Naohiro Hashimoto, Kei Sakata, Yoshiya Tanaka","doi":"10.55563/clinexprheumatol/ziktdx","DOIUrl":"10.55563/clinexprheumatol/ziktdx","url":null,"abstract":"<p><strong>Objectives: </strong>Monocytes are known to be involved in both adaptive and innate immune responses, though their roles in the pathogenesis of systemic lupus erythematosus (SLE) are still unclear. Here, we performed phenotypic and functional analyses of each monocyte subset.</p><p><strong>Methods: </strong>Peripheral blood from patients with autoimmune diseases (SLE: n=53, rheumatoid arthritis: n=12, systemic sclerosis: n=36) was analysed using flow cytometry to compare the number of each monocyte subset and the expression levels of the cell surface markers of patients to those of healthy donors (n=28).</p><p><strong>Results: </strong>The number of CD14dimCD16+ non-classical monocytes in peripheral blood from SLE patients was significantly decreased compared with those from healthy donors and patients with other autoimmune diseases. The number of circulating non-classical monocytes was inversely correlated to SLE disease activity. The number of non-classical monocytes was not related to the use of glucocorticoids or to the presence or absence of specific tissue inflammation. The expression levels of cell surface molecules and the survival rate of non-classical monocytes of patients with SLE were similar to those of healthy donors. An in vitro functional assay revealed that non-classical monocytes suppressed IFN-α production from PBMCs or plasmacytoid DCs, and cell-cell contact through ICAM-4 seemed to be important in this process.</p><p><strong>Conclusions: </strong>Our study demonstrated that the number of circulating non-classical monocytes, which has been shown to have the ability to suppress IFN-α production, was decreased in SLE patients, and this might be related to the excess IFN signature in SLE patients.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1568-1576"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}