Pub Date : 2025-10-15DOI: 10.1016/S2665-9913(25)00215-2
Shaozhe Cai , Yu Chen , Cong Ye , Umehara Hisanori , Jishuai Zhang , Ziwei Hu , Wei Sun , Lingli Dong
{"title":"Anti-BCMA CAR-T for the treatment of IgG4-related disease: clinical assessment and single-cell transcriptomic analysis","authors":"Shaozhe Cai , Yu Chen , Cong Ye , Umehara Hisanori , Jishuai Zhang , Ziwei Hu , Wei Sun , Lingli Dong","doi":"10.1016/S2665-9913(25)00215-2","DOIUrl":"10.1016/S2665-9913(25)00215-2","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 12","pages":"Pages e834-e836"},"PeriodicalIF":16.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-15DOI: 10.1016/S2665-9913(25)00184-5
Joshua L Bennett PhD , Kieren G Hollingsworth PhD , Arthur G Pratt PhD , Abbie E A Degnan MSc , Prof Gráinne S Gorman MD , Catherine Feeney MClin Res , Najib Naamane MSc , Jérémie Nsengimana PhD , Prof Avan A Sayer PhD , Amy E Anderson PhD , Prof John D Isaacs PhD
<div><h3>Background</h3><div>Rheumatoid arthritis increases the risk of generalised muscle wasting, with chronic inflammation contributing to the loss of muscle mass and strength. Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, increases serum creatinine concentrations without conclusive evidence of nephrotoxicity. In the Rheumatoid Arthritis and Muscle (RAMUS) study, we investigated whether tofacitinib affects muscle volume, strength, and function.</div></div><div><h3>Methods</h3><div>RAMUS was a prospective, single-arm, single-centre, proof of concept experimental study, done at Freeman Hospital, Newcastle upon Tyne, UK. Patients aged older than 18 years, with rheumatoid arthritis (according to the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology [ACR–EULAR] classification criteria for rheumatoid arthritis) initiating tofacitinib as standard care were recruited. Additional inclusion criteria were at least one sarcopenia risk factor, no previous treatment with JAK inhibitors, no systemic glucocorticoid treatment for at least 4 weeks before the baseline visit, and serum creatinine 1·5 times the upper limit of normal or less. Participants provided blood samples at baseline, 1 month, and 6 months; vastus lateralis biopsies were performed at baseline and 6 months. The primary outcome was change in lower limb muscle volume, assessed by quantitative MRI at baseline and after 1 and 6 months of tofacitinib treatment, and was assessed in all participants who completed the study. Secondary outcomes included changes in serum creatinine, appendicular lean mass index, muscle strength, muscle function, and disease activity (Disease Activity Score 28-C-reactive Protein [DAS28-CRP] score). Adverse events were recorded. People with lived experience with rheumatoid arthritis were involved in the design and set-up phases of this study. RAMUS was registered with ISRCTN (ISRCTN13364395).</div></div><div><h3>Findings</h3><div>Between Jan 21, 2021, and March 1, 2023, 22 patients were screened, and 15 (68%) were eligible and completed the study. 13 (87%) of 15 patients were female, two (13%) were male, 12 (80%) were White, and the mean age was 59·6 years (SD 10·0). After 6 months, tofacitinib treatment was associated with significant increases in lower limb muscle volume (mean increase 242 cm<sup>3</sup> [95% CI 44–441], p=0·017), particularly in the thigh, and significant increases in serum creatinine (p=0·0011). Disease activity (DAS28-CRP) was significantly reduced after 1 month of tofacitinib treatment (p=0·0064) with no further changes at 6 months. No significant changes in appendicular lean mass index, muscle strength, or muscle function were observed. 28 adverse events were recorded in 13 (87%) of 15 participants; one event was classified as severe and serious, and concerned a participant being hospitalised with COVID-19 pneumonitis before commencing tofacitinib.</div></div><div><h3>Inte
{"title":"Skeletal muscle effects of Janus kinase inhibition in rheumatoid arthritis (RAMUS): a single-arm, experimental medicine study","authors":"Joshua L Bennett PhD , Kieren G Hollingsworth PhD , Arthur G Pratt PhD , Abbie E A Degnan MSc , Prof Gráinne S Gorman MD , Catherine Feeney MClin Res , Najib Naamane MSc , Jérémie Nsengimana PhD , Prof Avan A Sayer PhD , Amy E Anderson PhD , Prof John D Isaacs PhD","doi":"10.1016/S2665-9913(25)00184-5","DOIUrl":"10.1016/S2665-9913(25)00184-5","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis increases the risk of generalised muscle wasting, with chronic inflammation contributing to the loss of muscle mass and strength. Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, increases serum creatinine concentrations without conclusive evidence of nephrotoxicity. In the Rheumatoid Arthritis and Muscle (RAMUS) study, we investigated whether tofacitinib affects muscle volume, strength, and function.</div></div><div><h3>Methods</h3><div>RAMUS was a prospective, single-arm, single-centre, proof of concept experimental study, done at Freeman Hospital, Newcastle upon Tyne, UK. Patients aged older than 18 years, with rheumatoid arthritis (according to the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology [ACR–EULAR] classification criteria for rheumatoid arthritis) initiating tofacitinib as standard care were recruited. Additional inclusion criteria were at least one sarcopenia risk factor, no previous treatment with JAK inhibitors, no systemic glucocorticoid treatment for at least 4 weeks before the baseline visit, and serum creatinine 1·5 times the upper limit of normal or less. Participants provided blood samples at baseline, 1 month, and 6 months; vastus lateralis biopsies were performed at baseline and 6 months. The primary outcome was change in lower limb muscle volume, assessed by quantitative MRI at baseline and after 1 and 6 months of tofacitinib treatment, and was assessed in all participants who completed the study. Secondary outcomes included changes in serum creatinine, appendicular lean mass index, muscle strength, muscle function, and disease activity (Disease Activity Score 28-C-reactive Protein [DAS28-CRP] score). Adverse events were recorded. People with lived experience with rheumatoid arthritis were involved in the design and set-up phases of this study. RAMUS was registered with ISRCTN (ISRCTN13364395).</div></div><div><h3>Findings</h3><div>Between Jan 21, 2021, and March 1, 2023, 22 patients were screened, and 15 (68%) were eligible and completed the study. 13 (87%) of 15 patients were female, two (13%) were male, 12 (80%) were White, and the mean age was 59·6 years (SD 10·0). After 6 months, tofacitinib treatment was associated with significant increases in lower limb muscle volume (mean increase 242 cm<sup>3</sup> [95% CI 44–441], p=0·017), particularly in the thigh, and significant increases in serum creatinine (p=0·0011). Disease activity (DAS28-CRP) was significantly reduced after 1 month of tofacitinib treatment (p=0·0064) with no further changes at 6 months. No significant changes in appendicular lean mass index, muscle strength, or muscle function were observed. 28 adverse events were recorded in 13 (87%) of 15 participants; one event was classified as severe and serious, and concerned a participant being hospitalised with COVID-19 pneumonitis before commencing tofacitinib.</div></div><div><h3>Inte","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 1","pages":"Pages e42-e52"},"PeriodicalIF":16.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/S2665-9913(25)00158-4
Gregory C McDermott MD , Ritu Gill MD , Suzanne Byrne MD , Staci Gagne MD , Xiaosong Wang MSc , Misti L Paudel PhD , Emily Kowalski BS , Grace Qian BA&Sc , Katarina Bade BS , Kevin Mueller BS , Alene Saavedra BA , Kathleen M M Vanni BA , Liya S Getachew MD , Caleb Bolden BA , Lauren A O'Keeffe BS , Natalie A Davis MSc , Alison Puri BA , Tina Mahajan MD , Erica Mulcaire-Jones MD , Neda Kortam BA , Jeffrey A Sparks MD
<div><h3>Background</h3><div>Evaluation of risk factors and screening strategies for rheumatoid arthritis-associated interstitial lung disease (ILD) in patients with early rheumatoid arthritis has been scarce. We investigated the prevalence of rheumatoid arthritis-associated ILD, risk factors, and the performance of proposed screening methods for rheumatoid arthritis-associated ILD in patients with early rheumatoid arthritis.</div></div><div><h3>Methods</h3><div>We performed a cross-sectional analysis of the prospective Study of Inflammatory Arthritis and Interstitial Lung Disease in Early RA (SAIL-RA). Study participants were eligible for inclusion if diagnosed with early rheumatoid arthritis, defined as being within 2 years of a diagnosis. Exclusions were pregnancy at enrolment or inability or unwillingness to obtain high-resolution CT (HRCT) chest imaging. Participants were enrolled at five academic health-care centres in the USA and assessed through surveys, medical history, HRCT chest imaging, pulmonary function tests, and laboratory testing for autoantibodies. Rheumatoid arthritis-associated ILD was identified through independent review of HRCTs by thoracic radiologists. We investigated risk factors for rheumatoid arthritis-associated ILD using multivariable logistic regression and reported the predictive performance of screening strategies for rheumatoid arthritis-associated ILD (from the ANCHOR-RA study; the 2023 guidelines from the American College of Rheumatology and American College of Chest Physicians [ACR–CHEST]; a four-factor risk score proposed in 2023; Sociedad Española de Reumatología and Sociedad Española de Neumología y Cirugía Torácica criteria; criteria proposed by Paulin and colleagues; and criteria derived from the ESPOIR cohort). The primary outcome was the presence of rheumatoid arthritis-associated ILD.</div></div><div><h3>Findings</h3><div>Participants were recruited between May 1, 2017, and Feb 22, 2024. Of 191 patients who were assessed for eligibility and included in the SAIL-RA cohort, 172 completed HRCT chest imaging and were included in this analysis: 128 (74%) were female, 44 (26%) were male, mean age was 55·3 years (SD 13·7), 126 (74%) of 171 were anti-cyclic citrullinated peptide (CCP) positive, 116 (68%) of 170 were rheumatoid factor positive, and median rheumatoid arthritis duration was 0·79 years (IQR 0·36–1·60); 19 (11%) had rheumatoid arthritis-associated ILD on HRCT. Factors associated with rheumatoid arthritis-associated ILD included moderate or high rheumatoid arthritis disease activity, determined by Disease Activity Score using 28 joints with erythrocyte sedimentation rate more than or equal to 3·2 (adjusted odds ratio [aOR] 7·00 [95% CI 1·95–25·13] <em>vs</em> remission or low disease activity) and age of 60 years or older (aOR 3·87 [1·33–11·27] <em>vs</em> age <60 years). Sensitivity of screening strategies ranged from 0·05 (95% CI 0·00–0·15) with the Paulin criteria (four-point cutoff) to 1·00 (
背景：早期类风湿关节炎患者类风湿关节炎相关间质性肺疾病（ILD）的危险因素评估和筛查策略很少。我们调查了类风湿关节炎相关ILD的患病率，危险因素，以及在早期类风湿关节炎患者中类风湿关节炎相关ILD筛查方法的表现。方法：我们对早期类风湿关节炎和间质性肺疾病的前瞻性研究（SAIL-RA）进行了横断面分析。如果研究参与者被诊断为早期类风湿关节炎（定义为诊断后2年内），则有资格纳入研究。排除入组时怀孕或不能或不愿意获得高分辨率CT （HRCT）胸部成像。参与者在美国的五个学术保健中心登记，并通过调查、病史、HRCT胸部成像、肺功能测试和自身抗体实验室测试进行评估。类风湿关节炎相关ILD由胸科放射科医师通过hrct的独立审查确定。我们使用多变量logistic回归研究了类风湿关节炎相关ILD的危险因素，并报告了类风湿关节炎相关ILD筛查策略的预测性能(来自ANCHOR-RA研究；美国风湿病学会和美国胸科医师学会2023年指南[ACR-CHEST]； 2023年提出的四因素风险评分；Sociedad Española de Reumatología和Sociedad Española de Neumología y Cirugía Torácica标准；Paulin及其同事提出的标准；和来自ESPOIR队列的标准)。主要结局是类风湿关节炎相关ILD的存在。研究结果：参与者是在2017年5月1日至2024年2月22日期间招募的。在191例评估合格并纳入saill - ra队列的患者中，172例完成HRCT胸部成像并纳入本分析：女性128例（74%），男性44例（26%），平均年龄54.3岁（SD 13.7）， 171例中126例（74%）抗环氨酸肽（CCP）阳性，170例中116例（68%）类风湿因子阳性，中位类风湿关节炎病程0.79年（IQR 0.36 - 0.60）；HRCT显示19例（11%）有类风湿关节炎相关ILD。类风湿关节炎相关ILD的相关因素包括中度或高度类风湿关节炎疾病活动性，由28个关节的疾病活动性评分确定，红细胞沉降率大于或等于3.2（校正优势比[aOR] 7.00 [95% CI 1.95 - 25.13] vs缓解或低疾病活动性）和年龄≥60岁（aOR为3.87 [1.33 - 11.27]vs年龄）。在这些早期类风湿关节炎患者中，11%患有类风湿关节炎相关的ILD。中度或高度疾病活动度和年龄在60岁或以上与类风湿关节炎相关的ILD在早期类风湿关节炎中密切相关。一些建议的筛查策略使用常规的因素在护理点显示有希望检测类风湿关节炎相关的ILD在早期类风湿关节炎。资助：美国国立卫生研究院/国家关节炎、肌肉骨骼和皮肤疾病研究所、风湿病研究基金会、内布拉斯加大学医学中心和内布拉斯加大学卫生系统。
{"title":"Risk factors for interstitial lung disease in early rheumatoid arthritis and external validation of screening strategies: a cross-sectional analysis of the prospective SAIL-RA cohort in the USA","authors":"Gregory C McDermott MD , Ritu Gill MD , Suzanne Byrne MD , Staci Gagne MD , Xiaosong Wang MSc , Misti L Paudel PhD , Emily Kowalski BS , Grace Qian BA&Sc , Katarina Bade BS , Kevin Mueller BS , Alene Saavedra BA , Kathleen M M Vanni BA , Liya S Getachew MD , Caleb Bolden BA , Lauren A O'Keeffe BS , Natalie A Davis MSc , Alison Puri BA , Tina Mahajan MD , Erica Mulcaire-Jones MD , Neda Kortam BA , Jeffrey A Sparks MD","doi":"10.1016/S2665-9913(25)00158-4","DOIUrl":"10.1016/S2665-9913(25)00158-4","url":null,"abstract":"<div><h3>Background</h3><div>Evaluation of risk factors and screening strategies for rheumatoid arthritis-associated interstitial lung disease (ILD) in patients with early rheumatoid arthritis has been scarce. We investigated the prevalence of rheumatoid arthritis-associated ILD, risk factors, and the performance of proposed screening methods for rheumatoid arthritis-associated ILD in patients with early rheumatoid arthritis.</div></div><div><h3>Methods</h3><div>We performed a cross-sectional analysis of the prospective Study of Inflammatory Arthritis and Interstitial Lung Disease in Early RA (SAIL-RA). Study participants were eligible for inclusion if diagnosed with early rheumatoid arthritis, defined as being within 2 years of a diagnosis. Exclusions were pregnancy at enrolment or inability or unwillingness to obtain high-resolution CT (HRCT) chest imaging. Participants were enrolled at five academic health-care centres in the USA and assessed through surveys, medical history, HRCT chest imaging, pulmonary function tests, and laboratory testing for autoantibodies. Rheumatoid arthritis-associated ILD was identified through independent review of HRCTs by thoracic radiologists. We investigated risk factors for rheumatoid arthritis-associated ILD using multivariable logistic regression and reported the predictive performance of screening strategies for rheumatoid arthritis-associated ILD (from the ANCHOR-RA study; the 2023 guidelines from the American College of Rheumatology and American College of Chest Physicians [ACR–CHEST]; a four-factor risk score proposed in 2023; Sociedad Española de Reumatología and Sociedad Española de Neumología y Cirugía Torácica criteria; criteria proposed by Paulin and colleagues; and criteria derived from the ESPOIR cohort). The primary outcome was the presence of rheumatoid arthritis-associated ILD.</div></div><div><h3>Findings</h3><div>Participants were recruited between May 1, 2017, and Feb 22, 2024. Of 191 patients who were assessed for eligibility and included in the SAIL-RA cohort, 172 completed HRCT chest imaging and were included in this analysis: 128 (74%) were female, 44 (26%) were male, mean age was 55·3 years (SD 13·7), 126 (74%) of 171 were anti-cyclic citrullinated peptide (CCP) positive, 116 (68%) of 170 were rheumatoid factor positive, and median rheumatoid arthritis duration was 0·79 years (IQR 0·36–1·60); 19 (11%) had rheumatoid arthritis-associated ILD on HRCT. Factors associated with rheumatoid arthritis-associated ILD included moderate or high rheumatoid arthritis disease activity, determined by Disease Activity Score using 28 joints with erythrocyte sedimentation rate more than or equal to 3·2 (adjusted odds ratio [aOR] 7·00 [95% CI 1·95–25·13] <em>vs</em> remission or low disease activity) and age of 60 years or older (aOR 3·87 [1·33–11·27] <em>vs</em> age <60 years). Sensitivity of screening strategies ranged from 0·05 (95% CI 0·00–0·15) with the Paulin criteria (four-point cutoff) to 1·00 (","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 12","pages":"Pages e851-e863"},"PeriodicalIF":16.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/S2665-9913(25)00252-8
Clément Triaille PhD , Prof Patrick Durez MD , Francesco Natalucci MD , Prof Rik Lories PhD , Prof Peter C Taylor PhD
Synovial tissue is widely considered to be a strong candidate for contributing to the development of individualised therapeutic strategies for the treatment and management of rheumatoid arthritis. Recently, several factors have enabled major developments in synovial tissue analysis: (1) improvement in synovial tissue biopsy techniques; (2) availability of powerful biotechnologies with increasing granularity; (3) recruitment of larger cohorts of patients; (4) development of recommendations to standardise synovial tissue analysis; and (5) an expanded therapeutic armamentarium of targeted therapies. Although recent studies have suggested the existence of rheumatoid arthritis subtypes based on the synovial tissue inflammatory profile, with potential therapeutic implications, other studies have yielded different results. In this Viewpoint we discuss and contextualise the findings of recent major studies in the field of synovial tissue. We highlight how disease activity, synovial tissue inflammatory burden, and response to therapy are interdependent features in rheumatoid arthritis, both earlier and later in the disease course. From there, we discuss how this multidirectional relationship has impacted (and potentially influenced the interpretation of) the findings of synovial tissue-based studies. Finally, we discuss the different hypotheses explaining the link between synovial tissue, clinical features, and therapeutic response.
{"title":"The relationship between clinical disease activity, synovial inflammatory profile, and treatment response in rheumatoid arthritis","authors":"Clément Triaille PhD , Prof Patrick Durez MD , Francesco Natalucci MD , Prof Rik Lories PhD , Prof Peter C Taylor PhD","doi":"10.1016/S2665-9913(25)00252-8","DOIUrl":"10.1016/S2665-9913(25)00252-8","url":null,"abstract":"<div><div>Synovial tissue is widely considered to be a strong candidate for contributing to the development of individualised therapeutic strategies for the treatment and management of rheumatoid arthritis. Recently, several factors have enabled major developments in synovial tissue analysis: (1) improvement in synovial tissue biopsy techniques; (2) availability of powerful biotechnologies with increasing granularity; (3) recruitment of larger cohorts of patients; (4) development of recommendations to standardise synovial tissue analysis; and (5) an expanded therapeutic armamentarium of targeted therapies. Although recent studies have suggested the existence of rheumatoid arthritis subtypes based on the synovial tissue inflammatory profile, with potential therapeutic implications, other studies have yielded different results. In this Viewpoint we discuss and contextualise the findings of recent major studies in the field of synovial tissue. We highlight how disease activity, synovial tissue inflammatory burden, and response to therapy are interdependent features in rheumatoid arthritis, both earlier and later in the disease course. From there, we discuss how this multidirectional relationship has impacted (and potentially influenced the interpretation of) the findings of synovial tissue-based studies. Finally, we discuss the different hypotheses explaining the link between synovial tissue, clinical features, and therapeutic response.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 1","pages":"Pages e66-e73"},"PeriodicalIF":16.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/S2665-9913(25)00183-3
Javier Narváez
{"title":"ILD risk prediction in routine care for rheumatoid arthritis","authors":"Javier Narváez","doi":"10.1016/S2665-9913(25)00183-3","DOIUrl":"10.1016/S2665-9913(25)00183-3","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 12","pages":"Pages e827-e829"},"PeriodicalIF":16.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/S2665-9913(25)00251-6
John D Pauling PhD , Prof Yannick Allanore PhD , Prof Maya H Buch PhD , Prof Maurizio Cutolo PhD , Prof Francesco Del Galdo PhD , Prof Christopher P Denton PhD , Stefano Di Donato MSc , Robyn T Domsic MD , Tracy Frech MD , Prof Ariane L Herrick MD , Prof Marco Matucci-Cerinic PhD , Prof Vanessa Smith PhD , Prof Marie-Elise Truchetet PhD , Michael Hughes PhD
Immune-mediated vascular endothelial injury is considered one of the earliest pathological features in systemic sclerosis and is thought to occur simultaneously within a broad range of organs, although typically clinically manifesting only as Raynaud's phenomenon in the early stages. Overt vascular systemic sclerosis manifestations include Raynaud's phenomenon, abnormal nailfold capillary morphology, digital ulcers, pulmonary arterial hypertension, cardiovascular disease (primary and coronary), telangiectasia, renal crisis, and gastric antral vascular ectasia. Tissue ischaemia might also contribute to aberrant tissue remodelling, resulting in calcinosis and fibrosis. Recognition of the substantial inter-relationship between these vascular complications is growing; examples of vascular treatment interventions targeting digital vasculopathy having off-target vascular benefits in other organs have been reported. In general, treatment of life-threatening vascular complications, such as pulmonary arterial hypertension, is not commenced until classifiable organ disease has occurred; however, the identification of robust prognostic biomarkers might allow such complications to be averted with preventative disease modification. In this Personal View, we describe the inter-relationship between vascular features of systemic sclerosis. We consider how these features might be exploited to establish a unified vascular conceptual framework that can inform the development of both predictive composite indices to guide preventative intervention, and a unified vascular composite endpoint model that can effectively capture clinically meaningful disease modification in future clinical trials of vasoactive treatments in systemic sclerosis.
{"title":"Exploiting a unified vascular framework to predict organ-specific complications and accomplish disease modification in systemic sclerosis","authors":"John D Pauling PhD , Prof Yannick Allanore PhD , Prof Maya H Buch PhD , Prof Maurizio Cutolo PhD , Prof Francesco Del Galdo PhD , Prof Christopher P Denton PhD , Stefano Di Donato MSc , Robyn T Domsic MD , Tracy Frech MD , Prof Ariane L Herrick MD , Prof Marco Matucci-Cerinic PhD , Prof Vanessa Smith PhD , Prof Marie-Elise Truchetet PhD , Michael Hughes PhD","doi":"10.1016/S2665-9913(25)00251-6","DOIUrl":"10.1016/S2665-9913(25)00251-6","url":null,"abstract":"<div><div>Immune-mediated vascular endothelial injury is considered one of the earliest pathological features in systemic sclerosis and is thought to occur simultaneously within a broad range of organs, although typically clinically manifesting only as Raynaud's phenomenon in the early stages. Overt vascular systemic sclerosis manifestations include Raynaud's phenomenon, abnormal nailfold capillary morphology, digital ulcers, pulmonary arterial hypertension, cardiovascular disease (primary and coronary), telangiectasia, renal crisis, and gastric antral vascular ectasia. Tissue ischaemia might also contribute to aberrant tissue remodelling, resulting in calcinosis and fibrosis. Recognition of the substantial inter-relationship between these vascular complications is growing; examples of vascular treatment interventions targeting digital vasculopathy having off-target vascular benefits in other organs have been reported. In general, treatment of life-threatening vascular complications, such as pulmonary arterial hypertension, is not commenced until classifiable organ disease has occurred; however, the identification of robust prognostic biomarkers might allow such complications to be averted with preventative disease modification. In this Personal View, we describe the inter-relationship between vascular features of systemic sclerosis. We consider how these features might be exploited to establish a unified vascular conceptual framework that can inform the development of both predictive composite indices to guide preventative intervention, and a unified vascular composite endpoint model that can effectively capture clinically meaningful disease modification in future clinical trials of vasoactive treatments in systemic sclerosis.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 12","pages":"Pages e895-e906"},"PeriodicalIF":16.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-30DOI: 10.1016/S2665-9913(25)00231-0
Ryan Malcolm Hum MBChB , Maria Christofi PhD , Samantha Louise Smith PhD , Lysette Michele Marshall MSc , Darren Plant PhD , Sebastien Viatte PhD , Prof Pauline Ho PhD , Paul Martin PhD , Prof Anne Barton PhD
Although psoriatic arthritis and rheumatoid arthritis are both common types of inflammatory arthritis characterised by synovial inflammation, there are distinct molecular and cellular landscapes between these conditions. Recent advances in synovial research in psoriatic arthritis have begun to unlock important insights into disease pathogenesis and potential clinical applications. For example, studies using high-dimensional technologies have identified psoriatic arthritis-specific macrophage, fibroblast, and mast cell subsets, as well as specific cytokines, such as IL-36 and IL-41, that drive pathogenesis. This Review explores how research of the synovium has advanced the understanding of psoriatic arthritis, the potential of identified cell types and cytokines as biomarkers and novel therapeutic targets, how limited sample sizes in high-dimensional studies are hindering clinical translation, and the future directions for synovial research in psoriatic arthritis.
{"title":"Synovial immunopathology in psoriatic arthritis: cellular and molecular insights","authors":"Ryan Malcolm Hum MBChB , Maria Christofi PhD , Samantha Louise Smith PhD , Lysette Michele Marshall MSc , Darren Plant PhD , Sebastien Viatte PhD , Prof Pauline Ho PhD , Paul Martin PhD , Prof Anne Barton PhD","doi":"10.1016/S2665-9913(25)00231-0","DOIUrl":"10.1016/S2665-9913(25)00231-0","url":null,"abstract":"<div><div>Although psoriatic arthritis and rheumatoid arthritis are both common types of inflammatory arthritis characterised by synovial inflammation, there are distinct molecular and cellular landscapes between these conditions. Recent advances in synovial research in psoriatic arthritis have begun to unlock important insights into disease pathogenesis and potential clinical applications. For example, studies using high-dimensional technologies have identified psoriatic arthritis-specific macrophage, fibroblast, and mast cell subsets, as well as specific cytokines, such as IL-36 and IL-41, that drive pathogenesis. This Review explores how research of the synovium has advanced the understanding of psoriatic arthritis, the potential of identified cell types and cytokines as biomarkers and novel therapeutic targets, how limited sample sizes in high-dimensional studies are hindering clinical translation, and the future directions for synovial research in psoriatic arthritis.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 11","pages":"Pages e808-e822"},"PeriodicalIF":16.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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