RMD Open最新文献

{"title":"The metabolic score for insulin resistance predicts the risk of cardiovascular disease in patients with psoriatic arthritis: results from the 10-year prospective CARMA cohort.","authors":"Miguel A Gonzalez-Gay, Ivan Ferraz-Amaro, Santos Castañeda, Jose A Pinto Tasende, Miren Uriarte-Ecenarro, Zulema Plaza, Fernando Sánchez-Alonso, Carmen García Gómez, Carlos González-Juanatey, Javier Llorca","doi":"10.1136/rmdopen-2024-005352","DOIUrl":"10.1136/rmdopen-2024-005352","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the predictive value of the metabolic score for insulin resistance (METS-IR) in identifying patients with psoriatic arthritis (PsA) at high risk of cardiovascular (CV) events.</p><p><strong>Methods: </strong>Assessment of patients with PsA enrolled in the Spanish prospective CARdiovascular in ReuMAtology (CARMA) project. Baseline data from 500 PsA patients without a history of CV events, chronic kidney disease, diabetes mellitus or statin use at the baseline visit were analysed. Patients were prospectively followed for 10 years in rheumatology outpatient clinics at tertiary centres. The performance of the METS-IR in predicting CV events was evaluated. METS-IR was categorised into three groups: <2.25, 2.25-2.48 and >2.48.</p><p><strong>Results: </strong>Over 4788 patient-years of follow-up, 27 individuals experienced at least one CV event. The annualised incidence rate was 5.6 events per 1000 patient-years (95% CI: 3.7 to 8.2). PsA patients with CV events had significantly higher METS-IR scores than those without CV events (2.37±0.24 vs 2.26±0.19; p=0.01). In this regard, patients who had CV events were more commonly included in the METS-IR 2.25-2.48 and >2.48 categories than those without CV events (p=0.008). Adjusted regression models indicated that PsA patients with a METS-IR >2.48 at baseline had an increased risk of experiencing a CV event during the follow-up period.</p><p><strong>Conclusions: </strong>In PsA patients under close observation in rheumatology units included in the prospective CARMA project, METS-IR serves as a reliable prognostic predictor of CV.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased concentrations of C5a complement receptor antibodies are associated with relapse in eosinophilic granulomatosis with polyangiitis (EGPA).","authors":"Sebastian Klapa, Antje Müller, Sabrina Arnold, Andreas Koch, Anja Staehle, Wataru Kaehler, Harald Heidecke, Gabriela Riemekasten, Christian M Karsten, Peter Lamprecht","doi":"10.1136/rmdopen-2024-005323","DOIUrl":"10.1136/rmdopen-2024-005323","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental myositis: an optimised version of C-protein-induced myositis.","authors":"Margherita Giannini, Daniela Rovito, Mustapha Oulad-Abdelghani, Nadia Messaddeq, Léa Debrut, Giulia Quiring, Pascal Kessler, Anne-Laure Charles, Bernard Geny, Daniel Metzger, Gilles Laverny, Alain Meyer","doi":"10.1136/rmdopen-2024-004558","DOIUrl":"10.1136/rmdopen-2024-004558","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory myopathies (IM) are a group of severe autoimmune diseases, sharing some similarities, whose cause is unknown and treatment is empirical.While C-protein-induced myositis (CIM), the most currently used mouse model of IM, has removed some roadblocks to understand and improve the treatment of IM, it has only been partially characterised and its generation limited by poor reproducibility. This study aimed at optimising the generation and the characterisation of CIM.</p><p><strong>Methods: </strong>In silico analysis was run to identify the top three specific and immunogenic regions of C-protein. The cognate polypeptides were synthesised and used to immunise C57BL/6N mice. Grip strength, walking ability, serum creatine kinase levels and muscle pathology (histological and electron microscopic features) were assessed. Immune cell proportions and interferon signature in muscles were also determined.</p><p><strong>Results: </strong>Among the three C-protein polypeptides with the highest immunogenic score, immunisation with the amino acids 965-991 induced the most severe phenotype (experimental myositis (EM)) characterised by 37% decrease in strength, 36% increase in hind base width, 45% increase in serum creatine-kinase level and 80% increase in histological inflammatory score. Optical and electron microscopy revealed mononuclear cell infiltrate, myofibre necrosis, atrophy, major histocompatibility complex-I expression as well as sarcolemmal, sarcomeric and mitochondrial abnormalities. Autoantibodies targeting C-protein, proinflammatory T-lymphocytes, macrophages, and type I and II interferon-stimulated transcripts were detected within the muscle of EM mice.</p><p><strong>Conclusion: </strong>EM recapitulates the common hallmarks of IM. This costless, high throughput, reproducible and robust model, generated in the most commonly used background for genetically engineered mice, may foster preclinical research in IM.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients with systemic autoimmune rheumatic diseases remain at risk for hospitalisation for COVID-19 infection in the Omicron era (2022-2024): a retrospective cohort study.","authors":"Naomi J Patel, Shruthi Srivatsan, Emily N Kowalski, Andrew King, Xiaosong Wang, Kathleen Mm Vanni, Grace Qian, Jennifer S Hanberg, Katarina J Bade, Alene A Saavedra, Kevin T Mueller, Buuthien Hang, Zachary K Williams, Colebrooke Johnson, Madison Negron, Jeffrey A Sparks, Zachary S Wallace","doi":"10.1136/rmdopen-2024-005114","DOIUrl":"10.1136/rmdopen-2024-005114","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the risk factors for severe acute COVID-19 outcomes in the Omicron era among individuals with systemic autoimmune rheumatic diseases (SARDs).</p><p><strong>Methods: </strong>We identified patients with confirmed SARDs and COVID-19 (positive PCR and/or antigen test) from 1 September 2022 to 15 March 2024 in the Mass General Brigham healthcare system. We estimated the associations of baseline characteristics with the odds of hospitalisation due to COVID-19 infection, verified by medical record review, using multivariable logistic regression.</p><p><strong>Results: </strong>Of 2061 patients with SARDs and COVID-19 during the Omicron era (75% female, mean age 62.2 years), 134 (6.5%) were hospitalised due to COVID-19, mostly due to respiratory symptoms (84, 63%). Of those hospitalised, 11 (8%) required mechanical ventilation and 20 (15%) died. Older age (adjusted OR (aOR) 1.05 per year), Black race (vs White race, aOR 4.15), ever smoking (vs never, aOR 1.76), CD20 inhibitor use (vs antimalarial monotherapy, aOR 2.22) and glucocorticoid use (vs non-use, aOR 2.07) were significantly associated with higher odds of hospitalisation. Female sex (vs male, aOR 0.63), booster SARS-CoV-2 vaccination (vs initial series, aOR 0.49) and vaccination within either 3 months or 3-6 months prior to infection (aOR 0.41 and aOR 0.38, respectively, vs none within 12 months) were significantly associated with lower odds of hospitalisation.</p><p><strong>Conclusions: </strong>Some patients with SARDs remain at higher risk of severe COVID-19 in the Omicron era. Patients who are older, Black, have more comorbidities, use CD20 inhibitors and/or glucocorticoids, or have not been vaccinated recently may benefit from risk-mitigating strategies, including booster vaccines and pre-exposure prophylaxis.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major adverse cardiovascular, thromboembolic and malignancy events in the filgotinib rheumatoid arthritis and ulcerative colitis clinical development programmes.","authors":"Xavier Mariette, Sven Borchmann, Sandrine Aspeslagh, Zoltan Szekanecz, Christina Charles-Schoeman, Stefan Schreiber, Ernest Hs Choy, Laurent Peyrin-Biroulet, Marc Schmalzing, Yoshiya Tanaka, Hugo Ten Cate, René Westhovens, C Janneke van der Woude, Edmund V Ekoka Omoruyi, Margaux Faes, Tomasz Masior, Paul Van Hoek, Chris Watson, Christine Rudolph, Andreas Stallmach","doi":"10.1136/rmdopen-2024-005033","DOIUrl":"10.1136/rmdopen-2024-005033","url":null,"abstract":"<p><strong>Objectives: </strong>Long-term safety is fundamental for treatment decision-making. This integrated analysis of filgotinib clinical trials in rheumatoid arthritis (RA) and ulcerative colitis (UC) assessed adverse events of interest (AEI): major adverse cardiovascular events (MACE), venous thromboembolism (VTE) and malignancies.</p><p><strong>Methods: </strong>Data were integrated from all phase II and III trials that have investigated filgotinib 100 mg or 200 mg once daily in RA and UC to date.</p><p><strong>Results: </strong>Analyses represent >12 500 (RA) and >2800 (UC) patient-years of exposure (PYE) to filgotinib. Incidences of AEI in the integrated analysis population were low. Modest numerical increases in incidence rates occurred in patients aged ≥65 years, including MACE (patients with RA), and malignancies (excluding non-melanoma skin cancer (NMSC)) and NMSC (patients with RA or UC). VTE was rare; in patients with RA aged ≥65 years receiving filgotinib 200 mg, exposure-adjusted incidence rate (95% CI) for VTE was 0.3 (0.1, 0.8)/100 PYE; no VTE events occurred in patients with UC aged ≥65 years. In patients with RA aged ≥65 years, MACE incidence rates were identical between filgotinib 100 mg and 200 mg; rates of malignancies and NMSC were numerically higher with 200 mg compared with 100 mg.</p><p><strong>Conclusions: </strong>Data are consistent with previous overall safety analyses demonstrating low rates of AEI in the overall study population. Numerically increased rates of AEI occurred in patients aged ≥65 years; further data are needed to assess the effect of CV risk factors. Overall, in this analysis, there was no consistent filgotinib dose effect on AEI.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of upadacitinib in subgroups of patients with axial spondyloarthritis with early versus established disease.","authors":"Victoria Navarro-Compán, Filip Van den Bosch, Percival Degrava Sampaio-Barros, Andrew J K Östör, Bhumik Parikh, Koji Kato, Tianming Gao, Jayne Stigler, Sofia Ramiro","doi":"10.1136/rmdopen-2024-005110","DOIUrl":"10.1136/rmdopen-2024-005110","url":null,"abstract":"<p><strong>Objectives: </strong>Early disease activity control with targeted therapies may improve long-term outcomes in axial spondyloarthritis (axSpA). Here, we evaluated the efficacy of upadacitinib in patients with axSpA with shorter versus longer symptom durations.</p><p><strong>Methods: </strong>SELECT-AXIS 1 and 2 studies enrolled patients with radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) naïve to biologic disease-modifying antirheumatic drugs (bDMARD-naïve) and with an intolerance or inadequate response to bDMARD therapy. Patients were stratified by symptom duration (nr-axSpA: early vs established (≤2 vs >2 years=Assessment of SpondyloArthritis international Society (ASAS) definition) and shorter vs longer (≤5 vs >5 years); r-axSpA: ≤5 vs >5 years). Efficacy endpoints assessed through week 14 included the proportion of patients achieving Axial Spondyloarthritis Disease Activity Score and ASAS40 responses, among others. Across all endpoints, the efficacy of upadacitinib versus placebo was assessed by relative risk (RR), and the placebo-adjusted effect of upadacitinib between shorter versus longer symptom duration was assessed by the RR ratio.</p><p><strong>Results: </strong>At week 14, better responses were observed in patients treated with upadacitinib in all endpoints assessed compared with placebo, regardless of symptom duration. When comparing patients with early/shorter versus established/longer symptom durations, for all measures assessed, no statistically significant differences were observed except for the change from baseline in high-sensitivity C-reactive protein in the nr-axSpA group, with a better response in early disease (difference -8.2, 95% CI -14.9 to -1.6).</p><p><strong>Conclusion: </strong>Regarding short-term outcomes, both subgroups of patients (shorter axSpA symptom duration (≤2 years) and longer symptom duration (>2 years)) achieved comparable results when treated with upadacitinib.</p><p><strong>Trial registration number: </strong>NCT03178487 (SELECT-AXIS 1) and NCT04169373 (SELECT-AXIS 2).</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Getting prepared for the silver wave: challenges in conducting rheumatic and musculoskeletal disease research in older adults.","authors":"Saskia Truijen, Shennah Austen, Fabienne Magdelijns, Annelies Boonen, Marloes van Onna","doi":"10.1136/rmdopen-2024-005280","DOIUrl":"10.1136/rmdopen-2024-005280","url":null,"abstract":"<p><p>Research in older adults diagnosed with rheumatic and musculoskeletal diseases (RMDs) comes with unique challenges, as these patients often face consequences of ageing, such as multimorbidity, polypharmacy, and geriatric syndromes (eg, frailty). In this viewpoint, we highlight various clinical, ethical, regulatory and logistical challenges, including, among others, issues with the decision-making capacity of older adults regarding study participation. We emphasise the need for feasible strategies and protocols to enhance research inclusivity in order to ultimately improve evidence-based care for the growing population of older adults with RMDs.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EducAR: implementing a multicomponent strategy to improve therapeutic adherence in rheumatoid arthritis.","authors":"María Ahijón Lana, Francisca Sivera Mascaró, Antonio Fernández-Nebro, Sara Muntadas Castelló, Marina Pérez, Teresa Otón, María Jesús García de Yébenes, Loreto Carmona","doi":"10.1136/rmdopen-2024-004989","DOIUrl":"10.1136/rmdopen-2024-004989","url":null,"abstract":"<p><strong>Introduction: </strong>The EULAR points to consider (PtC) for reducing non-adherence need implementation.</p><p><strong>Objectives: </strong>To design, implement and evaluate a strategy based on the PtC to improve treatment adherence in rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>A multidisciplinary panel cocreated an intervention that was subsequently tested in a cluster trial, where centres were randomised to access the developed intervention or follow the standard of care (SOC). 6-month initiation and implementation adherence were measured in consecutive patients with <2 years of RA. The results were discussed among the centres assigned to the intervention to explore barriers and facilitators to implementation.</p><p><strong>Results: </strong>The intervention was a two-sided website. The items on the patient site mainly addressed disease and treatment education, self-management and peer support. The healthcare professional site has tutorials on communication to improve trust and adherence, plus shared decision-making aids. It was tested in 141 RA patients (67 control and 74 intervention). Both groups increased adherence at 6 months, mainly in the control group (48% to 67% vs 42% to 47% in the intervention group). Implementation had been very low in relation to barriers identified as lack of time, inadequate focus (exclusively for nurses) and consideration of the current SOC as adequate.</p><p><strong>Conclusion: </strong>Despite designing an intervention based on the best evidence, the results were inconclusive; the lack of a detected effect could be explained by the limited implementation, which was insufficient for the complexity of the changes required (change of culture).</p><p><strong>Trial register number: </strong>ClinicalTrials.gov ID NCT05425485.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a semi-quantitative method to assess interstitial lung disease severity and progression in systemic sclerosis by standard and low-dose HRCT scans.","authors":"Lucas Tschalèr, Suzana Jordan, Trond Mogens Aaløkken, Mike Becker, Cathrine Brunborg, Cosimo Bruni, Christian Clarenbach, Rucsandra Dobrota, Michael Thomas Durheim, Muriel Elhai, Thomas Frauenfelder, Håvard Fretheim, Torhild Garen, Oyvind Midtvedt, Carina Mihai, Øyvind Molberg, Oliver Distler, Anna-Maria Hoffmann-Vold","doi":"10.1136/rmdopen-2024-004938","DOIUrl":"10.1136/rmdopen-2024-004938","url":null,"abstract":"<p><strong>Background: </strong>While the presence of distinct imaging abnormalities by high-resolution CT (HRCT) defines interstitial lung disease (ILD), there is a relative lack of validated methods to quantify these abnormalities in clinical practice, limiting ILD severity and progression assessments. We aimed to validate a semi-quantitative method for lung fibrosis assessment in patients with systemic sclerosis associated ILD (SSc-ILD) by standard and low-dose HRCT, considering lung structure and function as integral components of ILD evaluation.</p><p><strong>Methods: </strong>SSc patients from Oslo and Zurich with HRCT images, pulmonary function tests, including forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the 6-minute walk test with oxygen (O₂) desaturation were enrolled. We validated the semi-quantitative fibrosis extent method by HRCT using criteria for content and construct validity, discrimination, sensitivity to change and feasibility, as well as inter- and intra-rater variability.</p><p><strong>Results: </strong>65 SSc patients from Zurich and 90 from Oslo were included. Significant correlations were observed between the extent of fibrosis on HRCT and FVC (r=-0.517, p<0.001), DLCO (r=-0.400, p<0.001) and O₂ desaturation (r=-0.500, p<0.001), indicating content, construct and criterion validity. Discrimination and sensitivity to change assessments showed moderate correlation with DLCO (r=-0.377, p=0.003) but not with FVC or O₂ desaturation. Inter- and intra-rater variability demonstrated excellent reliability (κ=0.891 and κ=0.996, respectively), with HRCT quantification averaging 9-15 min, indicating high feasibility.</p><p><strong>Conclusion: </strong>This study confirms that semi-quantitative fibrosis assessment of HRCT for SSc-ILD meets most validation criteria, supporting its use in clinical practice and showing additive value of structural to functional ILD assessment.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of peripheral CD8⁺ T cell activation with disease activity and treatment resistance in systemic lupus erythematosus.","authors":"Yuya Fujita, Shingo Nakayamada, Satoshi Kubo, Yusuke Miyazaki, Koshiro Sonomoto, Hiroaki Tanaka, Yoshiya Tanaka","doi":"10.1136/rmdopen-2024-005122","DOIUrl":"10.1136/rmdopen-2024-005122","url":null,"abstract":"<p><strong>Objective: </strong>Various immune-cell subsets intricately mediate the pathogenesis of systemic lupus erythematosus (SLE). However, the role of CD8⁺ T cells in SLE remains unclear. We investigated the proportions and characteristics of peripheral CD8⁺ T cells and their association with clinical manifestations of SLE.</p><p><strong>Methods: </strong>We retrospectively enrolled 211 patients with SLE and 48 age- and sex-matched healthy controls (HCs). Peripheral CD8⁺ T cells were analysed using flow cytometry. The primary endpoint was the comparison of peripheral CD8⁺ T cell subset characteristics between patients and HCs.</p><p><strong>Results: </strong>Patients with SLE (mean age, 42.3 years; women, 89% and mean disease duration, 112.8 months) had significantly higher proportions of naïve CD8⁺ T cells (CCR7⁺CD45RA⁺), CD8⁺ terminally differentiated effector memory cells (CCR7^-CD45RA⁺) and activated CD8⁺ T cells (CD38⁺HLA-DR⁺) in peripheral blood mononuclear cells than HCs (p<0.001). Activated CD8 <b>⁺</b> T cells produced granzyme B and interferon-γ, which correlated with serum double-stranded (ds) DNA antibodies (rs=0.3146, p<0.0001) and 50% haemolytic unit of complement (rs=-0.3215, p=0.0003), and were significantly increased in patients with active systemic, renal or haematological involvement (p<0.05). Cluster analysis-based subgroup classification based on CD8 cell differentiation and activation revealed a group with high numbers of activated CD8⁺ T cells, highly active SLE and organ damage, including active nephritis and persistently high cell counts after a 24-week treatment, indicating treatment resistance (high anti-dsDNA antibody titres and high glucocorticoid doses).</p><p><strong>Conclusion: </strong>In SLE, greater proportions of highly cytotoxic and proinflammatory activated CD8⁺ T cells in peripheral blood-modulated disease activity, organ damage and residual treatment resistance, presenting a potential treatment target.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}