Rheumatology最新文献_第6页

Impact of non-serious infections on medication interruptions, quality of life, and disease flares in patients with rheumatoid arthritis. 非严重感染对类风湿关节炎患者药物中断、生活质量和疾病发作的影响

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-19 DOI: 10.1093/rheumatology/keaf503

Heta Patel,Kelly Gavigan,Shilpa Venkatachalam,David Curtis,Laura Stradford,W Benjamin Nowell,Joshua F Baker,Fenglong Xie,Jeffrey R Curtis,Michael D George

{"title":"Impact of non-serious infections on medication interruptions, quality of life, and disease flares in patients with rheumatoid arthritis.","authors":"Heta Patel,Kelly Gavigan,Shilpa Venkatachalam,David Curtis,Laura Stradford,W Benjamin Nowell,Joshua F Baker,Fenglong Xie,Jeffrey R Curtis,Michael D George","doi":"10.1093/rheumatology/keaf503","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf503","url":null,"abstract":"OBJECTIVESPatients with rheumatoid arthritis (RA) are at an increased risk for serious infections, but less is known about more common, non-serious infections. We aimed to assess the frequency and characteristics of non-serious infections and their effect on medication interruptions, quality of life, and disease flares.METHODSWe remotely recruited adults with RA from July 2022 to July 2023 through a community rheumatology practice-based research network. Participants joined the ArthritisPower Registry (now PatientSpot) and completed a baseline survey and up to 6 monthly follow-up surveys, focused on patient-reported outcomes (PROs), infections, medication interruptions, and disease flares. The impact of infections was evaluated by comparing survey measures in those with vs without an infection.RESULTSWe recruited 351 patients with RA who contributed 1674 monthly observations. Patients reported 523 infections (31% of observations), most frequently upper respiratory infections. Although few infections led to emergency department visits or hospitalizations, infections frequently led to missed work (37%) or RA treatment interruptions (26%). RA treatment interruptions were more common in those with vs without healthcare encounters or antibiotic use (38% vs 12%) and in more severe vs less severe infections (47% vs 20%). Infections were associated with worse scores for PROMIS Fatigue but not PROMIS Function, Depression, or Ability to Participate Socially. Frequency of disease flares was greater in those with an infection who interrupted RA treatment, especially in patients receiving tumor necrosis factor inhibitors.CONCLUSIONInfections are common in patients with RA and frequently lead to medication interruptions. These infections are associated with greater fatigue and impaired work productivity and may contribute to more disease flares.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"16 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089868","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}

引用次数: 0

Association of systemic sclerosis with risk of premature ovarian insufficiency: a retrospective cohort study 系统性硬化症与卵巢功能不全风险的关联：一项回顾性队列研究

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-19 DOI: 10.1093/rheumatology/keaf479

Liyi Dai, Yu-Hsun Wang, Lin Zeng, James Cheng-Chung Wei, Rong Mu

{"title":"Association of systemic sclerosis with risk of premature ovarian insufficiency: a retrospective cohort study","authors":"Liyi Dai, Yu-Hsun Wang, Lin Zeng, James Cheng-Chung Wei, Rong Mu","doi":"10.1093/rheumatology/keaf479","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf479","url":null,"abstract":"Objectives Premature ovarian insufficiency (POI) is linked to an elevated risk of premature mortality. Nonetheless, evidence regarding the risk associated with POI in systemic sclerosis (SSc) is deficient. This study aimed to evaluate the risk of POI in SSc, offering insights to advance clinical management strategies. Methods Data from the US Collaborative Network in TriNetX regarding 61569984 females were used in this study. Data on females with SSc and without SSc aged 20–40 worldwide from 2005 to 2022 were gathered. Propensity score matching (PSM) was used to match demographic characteristics, medication, and comorbidities that may affect ovarian function to construct the SSc and matched non-SSc cohorts with a ratio of 1:1. The differences in incidents of POI between the two cohorts were compared. Results A total of 6417 female patients with SSc and 6417 matched individuals were included. The age of the SSc group was 31.9 ± 6.0 years. Patients with SSc were associated with an increased risk of POI compared with the control group [HR = 1.6, 95% CI (1.1–2.2), log-rank test p = 0.017]. This association was consistent across both white and black populations. Notably, the risk was especially increased for SSc aged 30–40 (HR = 1.8, 95% CI 1.2–2.8). Conclusions Our study indicates that SSc is associated with a 1.6 times higher risk of developing POI. It underscores the importance of early evaluation and ongoing surveillance of ovarian health to improve the quality of life in women with SSc.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"90 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089731","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}

引用次数: 0

Methyl-prednisolone plus methotrexate-based regime vs prednisone-based standard of care for giant cell arteritis: a propensity score study 甲基强的松龙加甲氨蝶呤治疗方案vs以强的松为基础的巨细胞动脉炎标准治疗：倾向评分研究

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-19 DOI: 10.1093/rheumatology/keaf499

Adriana Soto-Peleteiro, José Hernández-Rodríguez, Fátima Raad, Borja de Miguel, Leonor Acha, Marina Torio, Halbert Hernandez-Negrin, Verónica Gómez-Caverzaschi, Ioana Ruiz-Arruza, Olga Araujo, Sergio Prieto-González, Georgina Espígol-Frigolé, Maria C Cid, Guillermo Ruiz-Irastorza

{"title":"Methyl-prednisolone plus methotrexate-based regime vs prednisone-based standard of care for giant cell arteritis: a propensity score study","authors":"Adriana Soto-Peleteiro, José Hernández-Rodríguez, Fátima Raad, Borja de Miguel, Leonor Acha, Marina Torio, Halbert Hernandez-Negrin, Verónica Gómez-Caverzaschi, Ioana Ruiz-Arruza, Olga Araujo, Sergio Prieto-González, Georgina Espígol-Frigolé, Maria C Cid, Guillermo Ruiz-Irastorza","doi":"10.1093/rheumatology/keaf499","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf499","url":null,"abstract":"Objectives Treatment of giant cell arteritis (GCA) still requires substantial exposure to glucocorticoids (GC), which are associated with significant toxicity. This study compares the efficacy and safety of the GC-only standard of care (SOC) with a regimen combining intravenous methyl-prednisolone (IVMP) pulses, methotrexate (MTX) and lower-doses of prednisone, in newly diagnosed patients with GCA. Methods A usual clinical practice study was conducted in three Spanish academic hospitals. 151 patients diagnosed with GCA were treated with SOC-prednisone (40–60 mg/d) or with IVMP (125–500 mg/d x3) followed by lower-dose prednisone (≤30 mg/d) and MTX (IVMP/MTX), with a follow-up of 2 years. A propensity score was used to adjust for baseline differences in the multivariate analyses. Results 79 (52.3%) patients received SOC-prednisone and 72 (47.7%) IVMP/MTX. The clinical characteristics at baseline were similar in both groups. 100% patients achieved remission after a median time of 4 weeks, without differences between groups. Relapse rates were also similar. Patients receiving IVMP/MTX had significantly lower cumulative GC doses and reached prednisone ≤5 mg/d faster than SOC patients (mean 13.8 vs 56.5 weeks; p&lt; 0.001). Patients in the IVMP/MTX group were less likely to suffer any GC-related adverse effect (adjusted OR 0.35, 95%CI 0.14–0.85; p= 0.021). Conclusions The combination IVMP/MTX with lower-dose prednisone is as effective as the SOC in inducing remission and preventing relapses in GCA. The IVMP/MTX scheme significantly reduces GC exposure and GC-associated adverse effects. IVMP/MTX could be a potential GC-sparing strategy, especially in patients with GCA at higher risk of GC toxicity.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"18 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089730","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}

引用次数: 0

Differences in spinal structural lesions between patients with early axSpA and non-axSpA chronic back pain: 2-year SPACE cohort results 早期axSpA和非axSpA慢性背痛患者脊柱结构病变的差异：2年SPACE队列结果

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-19 DOI: 10.1093/rheumatology/keaf500

Gizem Ayan, Liese de Bruin, Miranda van Lunteren, Manouk de Hooge, Ana Bento da Silva, Mary Lucy Marques, Monique Reijnierse, Victoria Navarro-Compán, Marleen van de Sande, Inger Jorid Berg, Roberta Ramonda, Sofia Exarchou, Désirée van der Heijde, Floris van Gaalen, Sofia Ramiro

{"title":"Differences in spinal structural lesions between patients with early axSpA and non-axSpA chronic back pain: 2-year SPACE cohort results","authors":"Gizem Ayan, Liese de Bruin, Miranda van Lunteren, Manouk de Hooge, Ana Bento da Silva, Mary Lucy Marques, Monique Reijnierse, Victoria Navarro-Compán, Marleen van de Sande, Inger Jorid Berg, Roberta Ramonda, Sofia Exarchou, Désirée van der Heijde, Floris van Gaalen, Sofia Ramiro","doi":"10.1093/rheumatology/keaf500","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf500","url":null,"abstract":"Objectives To compare spinal structural lesions on radiography and magnetic resonance imaging (MRI) over 2 years, between patients with early axial spondyloarthritis (axSpA) and non-axSpA chronic back pain. Methods Patients from the SPACE cohort with available radiography or MRI at both baseline and 2-year were included. Spinal lesions on radiography were assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), corner MRI lesions by the modified Canada-Denmark scoring system. Baseline spinal structural lesions and 2-year changes were compared between axSpA and non-axSpA. Generalized Estimating Equations were used to assess the change over 2-year, adjusting for age, sex, NSAID-use, and diagnosis. Results Radiography data from 318 patients (67% axSpA), MRI data from 351 patients (69% axSpA) were included. At baseline, the mean (SD) mSASSS was 0.6 (1.1) for both axSpA and non-axSpA. Over 2 years, mSASSS progression was minimal (0.01 units/year) in both groups. On MRI, axSpA patients had a mean of 1.4 (2.9) total structural lesions compared with 0.7 (2) in non-axSpA at baseline (p= 0.12). Significant 2Y increase in structural lesions [0.5 (1.8)] was mainly due to fat lesions [0.5 (1.6)] in axSpA. On MRI, fat lesions changed at a rate of 0.16 units/year in axSpA (p= 0.002), and -0.02 units/year in non-axSpA (p= 0.70). Conclusion Over 2 years, spinal structural damage typical for axSpA progressed minimally on radiography in axSpA and non-axSpA. On MRI, axSpA showed a significant increase in fat lesions, while non-axSpA had no progression. Fat lesions may be important to assess spinal changes from early disease onwards.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"37 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089729","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}

引用次数: 0

Elevated pre-eclampsia risk in lupus nephritis and antiphospholipid syndrome: a nationwide Spanish registry analysis 狼疮肾炎和抗磷脂综合征子痫前期风险升高：西班牙全国登记分析

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-19 DOI: 10.1093/rheumatology/keaf484

Mario Martín-Portugués, Jorge Esteban-Sampedro, Susana Mellor-Pita, Pablo Tutor de Ureta, Román Fernández-Guitián, Ana Huerta, Guillermo Ruiz-Irastorza, Luis Dueña-Bartolome, Ana Royuela, Alfonso Ortega-de la Puente, Marina de la Cruz-Echeandía, Víctor Moreno-Torres

{"title":"Elevated pre-eclampsia risk in lupus nephritis and antiphospholipid syndrome: a nationwide Spanish registry analysis","authors":"Mario Martín-Portugués, Jorge Esteban-Sampedro, Susana Mellor-Pita, Pablo Tutor de Ureta, Román Fernández-Guitián, Ana Huerta, Guillermo Ruiz-Irastorza, Luis Dueña-Bartolome, Ana Royuela, Alfonso Ortega-de la Puente, Marina de la Cruz-Echeandía, Víctor Moreno-Torres","doi":"10.1093/rheumatology/keaf484","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf484","url":null,"abstract":"Objective Evaluate the association of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE), focusing on lupus nephritis (LN), with risk of preeclampsia (PE) and PE with severity criteria (PESC). Methods Analysis of pregnant women admitted 2016–2022 in the Spanish Hospital Discharge Database. Factors associated with PE and PESC, including early-onset PE, severe PE, eclampsia, and HELLP syndrome, were evaluated. Results Among 1,973 249 admissions, 1,787 patients had SLE (9.1‰), with prior LN in 13.2%. SLE patients experienced higher PE (5.5% vs 2.1%) and PESC (2.1% vs 0.6%) rates; these rose further in SLE women with LN alone (PE: 16.9%, PESC: 5.2%) or with both LN and APS (PE: 18.2%, PESC: 13.6%) (p&lt; 0.05). Adjusted analyses showed PE and PESC were each associated with SLE (OR = 1.78, 95% CI 1.39–2.28; OR = 2.17, 95% CI 1.47–3.22), LN (OR = 1.94, 95% CI 1.18–3.19; OR = 2.45, 95% CI 1.18–5.09) and APS (OR = 1.53, 95% CI 1.28–1.84; OR = 1.91, 95% CI 1.44–2.54). Within SLE patients, baseline hypertension (OR = 4.27, 95% CI 2.45–7.44), LN (OR = 2.06, 95% CI 1.26–3.37) and APS (OR = 1.85, 95% CI 1.03–3.32) were linked to PE, while LN alone predicted PESC (OR = 2.88, 95% CI 1.41–5.91). Conclusion The risk of PE and PESC that patients with SLE exhibit is further amplified in those with a history of LN or APS. Recognizing SLE, APS and especially LN is crucial for precise risk stratification and tailored management to improve maternal and fetal outcomes.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"54 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089728","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}

引用次数: 0

SIRT3 inhibits fibroblast-like synoviocytes activation in rheumatoid arthritis through delactylation of H3K18 SIRT3通过H3K18去乙酰化抑制类风湿关节炎中成纤维细胞样滑膜细胞的激活

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-16 DOI: 10.1093/rheumatology/keaf497

Jianxiong Zheng, Chunhua Liu, Jiayao Hao, Min Tan, Jun Li, Yakun Yu, Jinyue Lu, Jing Mao, Hongxia Wang, Shen Haili

{"title":"SIRT3 inhibits fibroblast-like synoviocytes activation in rheumatoid arthritis through delactylation of H3K18","authors":"Jianxiong Zheng, Chunhua Liu, Jiayao Hao, Min Tan, Jun Li, Yakun Yu, Jinyue Lu, Jing Mao, Hongxia Wang, Shen Haili","doi":"10.1093/rheumatology/keaf497","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf497","url":null,"abstract":"Objectives Metabolic reprogramming and epigenetic modifications are key contributors to the development of rheumatoid arthritis (RA). Recent studies have identified lactate-dependent histone modifications as a novel epigenetic mechanism linking glycolysis to gene regulation. However, the precise role of histone lactylation in RA pathogenesis remains unclear. We aimed to elucidate the specific mechanism of histone lactylation, particularly H3K18la, in the pathogenesis of RA and to explore the therapeutic potential of the SIRT3-mediated delactylation process. Methods H3K18la levels in synovial tissue from RA patients were assessed using Western blot and immunohistochemistry. Collagen-induced arthritis (CIA) models combined with fibroblast-like synoviocytes (FLS) were used to explore H3K18la effects. CUT&Tag and RNA-seq identified pathways driven by H3K18la. SIRT3 function was validated using si-SIRT3 and the SIRT3 agonist honokiol in FLS. SIRT3 expression was assessed in peripheral blood mononuclear cells (PBMCs) from RA patients, and macrophage-FLS co-culture experiments evaluated SIRT3 knockdown effects. Results Lactylation, particularly H3K18la, was significantly elevated in the synovial tissue of RA patients. Reducing H3K18la alleviated CIA model-associated symptoms and mitigated TNF-α’s pathogenic effects on FLS, whereas increasing H3K18la exacerbated TNF-α–induced pathology. H3K18la and lactate co-regulated pathways included chemokine signalling and the inflammatory mediator of transient receptor potential channels. Furthermore, SIRT3, a key regulator of H3K18la, was downregulated in PBMCs from RA patients. Reduced SIRT3 increased H3K18la in FLS and macrophages, which activated FLS. Conclusions SIRT3 suppresses RA progression by delactylating H3K18. These findings may pave the way for novel lactylation-targeted therapies in RA.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"3 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089411","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}

引用次数: 0

A possible mechanism of facial contour and extremity deformity in paediatric patients with linear scleroderma. 线状硬皮病患儿面部轮廓和肢体畸形的可能机制。

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-15 DOI: 10.1093/rheumatology/keaf496

Guang-Ming Han,Yi-Fei Xu,Xi-Wen Zheng,Xiao-Yi Zhang,Zhao-Xia Li,Yuan-Zhen Lu,Fang Wang,Min-Shan Chen,Yu-Jian Zou

引用次数: 0

Hydroxychloroquine discontinuation in systemic lupus erythematosus: a retrospective cohort study with 3-year follow-up. 羟氯喹停药治疗系统性红斑狼疮：一项3年随访的回顾性队列研究。

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-15 DOI: 10.1093/rheumatology/keaf498

Milena Delai,Rachel B Simon,Eduardo M Cardoso,Vasileios Kyttaris

{"title":"Hydroxychloroquine discontinuation in systemic lupus erythematosus: a retrospective cohort study with 3-year follow-up.","authors":"Milena Delai,Rachel B Simon,Eduardo M Cardoso,Vasileios Kyttaris","doi":"10.1093/rheumatology/keaf498","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf498","url":null,"abstract":"OBJECTIVESTo evaluate the incidence and factors associated with systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) discontinuation.METHODSWe conducted a retrospective single-centre study of adult SLE patients who discontinued HCQ. Clinical and serological characteristics at baseline (time of HCQ discontinuation), were compared between patients who experienced flares (any, repeated, or severe) and those who remained flare-free during the follow-up, with a potential observation period of up to 36 months. Categorical variables were analysed using Fisher's exact test; continuous variables using appropriate tests based on normality and variance.RESULTSAmong 42 patients included, 12 (29%), 15 (36%), and 14 (38%) experienced a flare during the first, second, and third year, respectively. Over 36 months, 21 (50%) had at least one flare, 10 had a severe flare, and 8 had repeated flares. 19 patients remained flare-free. Low C3 levels at baseline were associated with any flare (p< 0.001), repeated flares (p< 0.001), and severe flares (p= 0.014) compared with those without flares. Patients with low C3 at baseline flared earlier and more frequently (log-rank p< 0.001) with hazard ratio of 10.18 (95%CI: 3.26-31.84, p< 0.001) for flaring, compared with those with normal C3. Other clinical and laboratory factors were not associated with flare prevention.CONCLUSIONHalf the patients who discontinued HCQ flared within two years. Low C3 levels at baseline were associated with increased risk of flares. These findings suggest that flares are common soon after HCQ discontinuation, and low C3 may help identify patients at higher risk for disease reactivation after HCQ discontinuation.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"31 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089871","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}

引用次数: 0

N-formyl methionine peptide-driven neutrophil activation in idiopathic inflammatory myopathies. 特发性炎性肌病中n -甲酰基蛋氨酸肽驱动的中性粒细胞活化。

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-15 DOI: 10.1093/rheumatology/keaf495

Jorge A Gonzalez-Chapa,Begum Horuluoglu,Antonella Notarnicola,Arpit Rathee,Noor Kaur,Ryan D Stultz,Lisa Christopher-Stine,Jemima Albayda,Inger Nennesmo,Ingrid E Lundberg,Christian Lood

{"title":"N-formyl methionine peptide-driven neutrophil activation in idiopathic inflammatory myopathies.","authors":"Jorge A Gonzalez-Chapa,Begum Horuluoglu,Antonella Notarnicola,Arpit Rathee,Noor Kaur,Ryan D Stultz,Lisa Christopher-Stine,Jemima Albayda,Inger Nennesmo,Ingrid E Lundberg,Christian Lood","doi":"10.1093/rheumatology/keaf495","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf495","url":null,"abstract":"OBJECTIVENeutrophil activation is heightened in inflammatory myopathies and associated with disease activity, yet its mechanisms remain unclear. This study explores the role of N-formyl methionine (fMET) in formyl peptide receptor 1 (FPR1)-mediated neutrophil activation in idiopathic inflammatory myopathies (IIMs), focusing on dermatomyositis (DM) and inclusion body myositis (IBM).METHODSPlasma from IBM (n = 46), DM (n = 40), and healthy controls (n = 40) was analyzed for fMET, calprotectin, neutrophil elastase DNA (NE-DNA), and cytokines using ELISA. Neutrophil markers CD11b and CD66b were assessed by flow cytometry following plasma stimulation with or without FPR1 inhibition. Correlation analyses were performed between fMET, muscle strength (MMT8), and neutrophil activation markers.RESULTSDM and IBM patients had significantly higher plasma fMET levels than controls (p< 0.0001 for DM; p= 0.0002 for IBM). Median fMET levels were 13 719 pg/ml (75th percentile: 17 236 pg/ml) for IBM, 14 780 pg/ml (75th percentile: 17 631 pg/ml) for DM, and 8,449 pg/ml (75th percentile: 12 632 pg/ml) for controls. fMET correlated inversely with MMT8 in antibody-negative IBM (r=-0.53, p= 0.02). Calprotectin was elevated in DM (p= 0.01) but not IBM; NE-DNA complexes were increased in both DM (p= 0.03) and IBM (p< 0.0001). FPR1 inhibition significantly reduced plasma-induced neutrophil activation in DM (p< 0.0001) and IBM (p= 0.0012), restoring CD66b and partially CD11b to control levels.CONCLUSIONOur findings show that fMET-FPR1 signalling drives neutrophil activation in DM and IBM, promoting inflammation and muscle damage. Targeting this pathway may offer a novel IIM therapy.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"38 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089872","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}

引用次数: 0

Impact of dactylitis and enthesitis resolution on disease control in guselkumab-treated PsA patients with TNFi-IR: COSMOS post-hoc analysis. 在guelkumab治疗的PsA患者中，手指炎和鼻炎消退对疾病控制的影响，伴有TNFi-IR: COSMOS事后分析。

IF 5.5 2区医学

Rheumatology Pub Date : 2025-09-14 DOI: 10.1093/rheumatology/keaf490

Helena Marzo-Ortega,Iain B McInnes,Mohamed Sharaf,Alen Zabotti,Emmanouil Rampakakis,Dennis McGonagle,Ahmed Abogamal,Pascal Richette,Georg Schett

{"title":"Impact of dactylitis and enthesitis resolution on disease control in guselkumab-treated PsA patients with TNFi-IR: COSMOS post-hoc analysis.","authors":"Helena Marzo-Ortega,Iain B McInnes,Mohamed Sharaf,Alen Zabotti,Emmanouil Rampakakis,Dennis McGonagle,Ahmed Abogamal,Pascal Richette,Georg Schett","doi":"10.1093/rheumatology/keaf490","DOIUrl":"https://doi.org/10.1093/rheumatology/keaf490","url":null,"abstract":"OBJECTIVETo evaluate guselkumab efficacy on dactylitis resolution (DR) and enthesitis resolution (ER), and their impact on subsequent disease control, in patients with active psoriatic arthritis (PsA) and prior inadequate response to tumour necrosis factor inhibitors (TNFi-IR).METHODSIn the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks until W44. The Dactylitis Severity Score (DSS) and Leeds Enthesitis Index (LEI) assessed dactylitis and enthesitis. This post-hoc analysis evaluated associations between W24 DR/ER and W48 achievement of stringent disease control measures using logistic regression.RESULTSAt baseline, 103/285 (36.1%) patients had dactylitis (DSS ≥ 1) and 190/285 (66.7%) had enthesitis (LEI ≥ 1). Patients with dactylitis were more likely to have enthesitis, more joint (SJC/DAPSA) and skin involvement, higher PGA score, and lower BMI vs those without dactylitis. Patients with enthesitis were more likely to be female, and have dactylitis, more joints affected (SJC/TJC/DAPSA) and worse physical functioning (HAQ-DI/SF-36 PCS) vs those without enthesitis. Greater proportions of guselkumab- vs placebo-treated patients achieved DR/ER (W24: 44.8%/39.7% vs 25.0%/18.8%); rates increased through W48 among guselkumab-randomized patients (67.2%/55.6%). W24 resolution was associated with W48 achievement of stringent measures, including ACR50/70, DAPSA LDA/remission, PASI100, PASDAS LDA/VLDA, and MDA/VLDA (odds ratios: DR, 3.28-13.38; ER, 2.88-6.09).CONCLUSIONGuselkumab treatment resulted in high DR/ER rates through W48 in TNFi-IR PsA patients. W24 DR/ER was associated with W48 disease control, providing valuable insights for clinical decision-making based on W24 treatment responses.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"54 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089876","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}

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