Susan Manzi, Ian N Bruce, Eric F Morand, Richard Furie, Yoshiya Tanaka, Kenneth C Kalunian, Anca Askanase, Patricia Puzio, Emon Khan, Jenny Wissmar, Michael Song, Catharina Lindholm, The Tulip-Sc Investigators
Objective: The multinational, phase 3, double-blind, placebo-controlled TULIP-SC trial evaluated the efficacy and safety of subcutaneous anifrolumab in adults who have moderate-to-severe SLE activity, despite receiving standard therapy.
Methods: Adults with SLE received subcutaneous anifrolumab 120 mg or placebo once weekly for 52 weeks (1:1 randomization). Only the primary endpoint (treatment difference in BILAG-based Composite Lupus Assessment [BICLA] response at 52 weeks) was formally tested in a pre-planned interim analysis; key secondary and other endpoints were tested in the full analysis.
Results: At the interim analysis (220 patients, anifrolumab: n=109; placebo: n=111), the primary endpoint was met (anifrolumab vs placebo: 59.4% vs 43.9%; BICLA response difference [95% confidence interval]=15.5% [2.3-28.6%], p=0.0211). The full analysis included 367 patients (anifrolumab: n=184; placebo: n=183). Versus placebo, more patients treated with anifrolumab attained a BICLA response whilst maintaining low/reduced oral glucocorticoid doses through Week 52 (56.2% vs 34.0%; difference=22.3% [12.3-32.2] p<0.0001), and the time to first sustained BICLA response was reduced (Hazard ratio=2.2 [1.5-3.2]; p<0.0001). Treatment differences in Week 52 DORIS remission and Low Lupus Disease Activity State attainment rates favored anifrolumab over placebo (14.2% [5.6-22.8%], p=0.0012, and 14.1% [4.6-23.6%], p=0.0038). The frequencies of serious adverse events were 11.9% with anifrolumab and 10.4% with placebo; the frequencies of herpes zoster were 3.8% and 1.1%, respectively.
Conclusion: Consistent with the well-established profile of intravenous anifrolumab, subcutaneous anifrolumab demonstrated significant, clinically meaningful treatment benefits when added to standard therapy, and an acceptable safety profile in patients with moderate to severe SLE.
目的：这项跨国、三期、双盲、安慰剂对照的TULIP-SC试验评估了皮下anfrolumab在接受标准治疗的中度至重度SLE患者中的疗效和安全性。方法：成人SLE患者接受皮下注射anfrolumab 120 mg或安慰剂，每周1次，共52周（1:1随机分组）。在预先计划的中期分析中，只有主要终点（52周时基于bilag的复合狼疮评估[BICLA]疗效的治疗差异）被正式测试；在完整的分析中测试了关键的次要终点和其他终点。结果：在中期分析（220例患者，anifrolumab: n=109；安慰剂：n=111）中，达到了主要终点（anifrolumab vs安慰剂：59.4% vs 43.9%； BICLA反应差[95%置信区间]=15.5% [2.3-28.6%],p=0.0211）。完整的分析包括367例患者（anifrolumab: n=184；安慰剂：n=183）。与安慰剂相比，更多接受anifrolumab治疗的患者在维持低/减少口服糖皮质激素剂量的情况下获得了BICLA反应（56.2% vs 34.0%；差异=22.3%[12.3-32.2]）。结论：与静脉注射anifrolumab的既定特征一致，皮下注射anifrolumab在标准治疗中显示出显着的、有临床意义的治疗益处，并且在中度至重度SLE患者中具有可接受的安全性。
{"title":"Efficacy and Safety of Subcutaneous Anifrolumab in Systemic Lupus Erythematosus: the Randomized, Phase 3, TULIP-SC Study.","authors":"Susan Manzi, Ian N Bruce, Eric F Morand, Richard Furie, Yoshiya Tanaka, Kenneth C Kalunian, Anca Askanase, Patricia Puzio, Emon Khan, Jenny Wissmar, Michael Song, Catharina Lindholm, The Tulip-Sc Investigators","doi":"10.1002/art.70041","DOIUrl":"https://doi.org/10.1002/art.70041","url":null,"abstract":"<p><strong>Objective: </strong>The multinational, phase 3, double-blind, placebo-controlled TULIP-SC trial evaluated the efficacy and safety of subcutaneous anifrolumab in adults who have moderate-to-severe SLE activity, despite receiving standard therapy.</p><p><strong>Methods: </strong>Adults with SLE received subcutaneous anifrolumab 120 mg or placebo once weekly for 52 weeks (1:1 randomization). Only the primary endpoint (treatment difference in BILAG-based Composite Lupus Assessment [BICLA] response at 52 weeks) was formally tested in a pre-planned interim analysis; key secondary and other endpoints were tested in the full analysis.</p><p><strong>Results: </strong>At the interim analysis (220 patients, anifrolumab: n=109; placebo: n=111), the primary endpoint was met (anifrolumab vs placebo: 59.4% vs 43.9%; BICLA response difference [95% confidence interval]=15.5% [2.3-28.6%], p=0.0211). The full analysis included 367 patients (anifrolumab: n=184; placebo: n=183). Versus placebo, more patients treated with anifrolumab attained a BICLA response whilst maintaining low/reduced oral glucocorticoid doses through Week 52 (56.2% vs 34.0%; difference=22.3% [12.3-32.2] p<0.0001), and the time to first sustained BICLA response was reduced (Hazard ratio=2.2 [1.5-3.2]; p<0.0001). Treatment differences in Week 52 DORIS remission and Low Lupus Disease Activity State attainment rates favored anifrolumab over placebo (14.2% [5.6-22.8%], p=0.0012, and 14.1% [4.6-23.6%], p=0.0038). The frequencies of serious adverse events were 11.9% with anifrolumab and 10.4% with placebo; the frequencies of herpes zoster were 3.8% and 1.1%, respectively.</p><p><strong>Conclusion: </strong>Consistent with the well-established profile of intravenous anifrolumab, subcutaneous anifrolumab demonstrated significant, clinically meaningful treatment benefits when added to standard therapy, and an acceptable safety profile in patients with moderate to severe SLE.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852778","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}
David. S. Pisetsky, Jennifer L. Rogers, Amanda M. Eudy, Katherine T. Martucci, Ru‐Rong Ji, Peter E. Lipsky
{"title":"Reply to the Letter to the Editor","authors":"David. S. Pisetsky, Jennifer L. Rogers, Amanda M. Eudy, Katherine T. Martucci, Ru‐Rong Ji, Peter E. Lipsky","doi":"10.1002/art.70040","DOIUrl":"https://doi.org/10.1002/art.70040","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"30 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829990","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}
Junxia Huang, Xue Han, Xiuyuan Wang, Liuting Huang, Manna Lin, Cheng Chen, Linzhu Kang, Yuqing Huang, Feifei Hu, Xinzhi Xu, Xue Yang, Ji Yang
Objectives Localized scleroderma (LoS) and systemic sclerosis (SSc) are both fibrotic diseases, but LoS is limited to the skin, whereas SSc involves systemic organ fibrosis. This study aimed to elucidate the mechanisms underlying these differences. Methods Skin biopsies from 3 healthy controls, 3 patients with LoS, and 3 patients with SSc underwent immunofluorescence and single‐cell RNA sequencing (scRNA‐seq). Key molecular functions were validated using in vitro assays and murine models. Results Immunofluorescence revealed a high prevalence of tertiary lymphoid structures (TLS) in LoS lesions (65.7%) compared to SSc (14.3%, p = 0.0013). scRNA‐seq identified T follicular helper (Tfh) cells enriched within TLS in LoS. Tfh cells likely promote B cell recruitment via the CXCL13/CXCR5 axis, and integrin α4 may support Tfh cell retention, contributing to TLS stability. These organized immune aggregates, together with elevated TGF‐β expression, may drive localized fibroblast activation and skin fibrosis in LoS. In contrast, SSc lesions contained fibroblasts with high CREB3L1 expression. CREB3L1 overexpression increased type I collagen, fibronectin 1, and periostin levels in fibroblasts, while knockdown reduced them. In a SSc mouse model, CREB3L1 upregulation worsened skin and lung fibrosis, whereas knockdown alleviated it. Conclusion These findings suggest that LoS fibrosis is driven by TLS‐mediated local immune activation, whereas the systemic activation of CREB3L1‐expressing fibroblasts plays an important role in SSc fibrosis. Targeting local inflammation may benefits LoS, while targeting CREB3L1 offers a promising antifibrotic strategy in SSc.
局限性硬皮病（LoS）和系统性硬化症（SSc）都是纤维化疾病，但LoS仅限于皮肤，而SSc涉及全身器官纤维化。本研究旨在阐明这些差异背后的机制。方法对3例健康对照、3例LoS患者和3例SSc患者的皮肤活检进行免疫荧光和单细胞RNA测序（scRNA - seq）。通过体外实验和小鼠模型验证了关键分子功能。结果免疫荧光显示，LoS病变中三级淋巴结构（TLS）的发生率（65.7%）高于SSc （14.3%, p = 0.0013）。scRNA‐seq鉴定了LoS中富含TLS的T滤泡辅助细胞（Tfh）。Tfh细胞可能通过CXCL13/CXCR5轴促进B细胞募集，而整合素α4可能支持Tfh细胞保留，有助于TLS的稳定性。这些有组织的免疫聚集体，连同TGF‐β表达的升高，可能驱动局部成纤维细胞激活和LoS中的皮肤纤维化。相反，SSc病变中含有高表达CREB3L1的成纤维细胞。CREB3L1过表达增加了成纤维细胞中I型胶原、纤维连接蛋白1和骨膜蛋白的水平，而敲低则降低了它们的水平。在SSc小鼠模型中，CREB3L1上调加重了皮肤和肺纤维化，而下调则减轻了这种情况。这些研究结果表明，LoS纤维化是由TLS介导的局部免疫激活驱动的，而表达CREB3L1的成纤维细胞的全身激活在SSc纤维化中起重要作用。靶向局部炎症可能有利于LoS，而靶向CREB3L1则为SSc提供了一种有希望的抗纤维化策略。
{"title":"Single‐Cell Profiling Reveals Divergent Mechanisms of Fibrosis in Localized Scleroderma and Systemic Sclerosis","authors":"Junxia Huang, Xue Han, Xiuyuan Wang, Liuting Huang, Manna Lin, Cheng Chen, Linzhu Kang, Yuqing Huang, Feifei Hu, Xinzhi Xu, Xue Yang, Ji Yang","doi":"10.1002/art.70039","DOIUrl":"https://doi.org/10.1002/art.70039","url":null,"abstract":"Objectives Localized scleroderma (LoS) and systemic sclerosis (SSc) are both fibrotic diseases, but LoS is limited to the skin, whereas SSc involves systemic organ fibrosis. This study aimed to elucidate the mechanisms underlying these differences. Methods Skin biopsies from 3 healthy controls, 3 patients with LoS, and 3 patients with SSc underwent immunofluorescence and single‐cell RNA sequencing (scRNA‐seq). Key molecular functions were validated using in vitro assays and murine models. Results Immunofluorescence revealed a high prevalence of tertiary lymphoid structures (TLS) in LoS lesions (65.7%) compared to SSc (14.3%, <jats:italic>p</jats:italic> = 0.0013). scRNA‐seq identified T follicular helper (Tfh) cells enriched within TLS in LoS. Tfh cells likely promote B cell recruitment via the <jats:italic>CXCL13/CXCR5</jats:italic> axis, and integrin α4 may support Tfh cell retention, contributing to TLS stability. These organized immune aggregates, together with elevated <jats:italic>TGF‐β</jats:italic> expression, may drive localized fibroblast activation and skin fibrosis in LoS. In contrast, SSc lesions contained fibroblasts with high CREB3L1 expression. CREB3L1 overexpression increased type I collagen, fibronectin 1, and periostin levels in fibroblasts, while knockdown reduced them. In a SSc mouse model, CREB3L1 upregulation worsened skin and lung fibrosis, whereas knockdown alleviated it. Conclusion These findings suggest that LoS fibrosis is driven by TLS‐mediated local immune activation, whereas the systemic activation of CREB3L1‐expressing fibroblasts plays an important role in SSc fibrosis. Targeting local inflammation may benefits LoS, while targeting CREB3L1 offers a promising antifibrotic strategy in SSc.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"25 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830299","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}
Noah Waller, Steven E Harte, Richard E Harris, Andrew Schrepf, Tristin Smith, Eric Ichesco, Chelsea Kaplan, Flavia Sunzini, Deeba Minhas, Wendy Marder, Sara R Till, David A Williams, Chad M Brummett, Neil Basu, Sawsan As‐Sanie, Daniel J Clauw
Objective Nociplastic pain is pain primarily driven by the central nervous system and, unlike nociceptive pain conditions, is thought to be refractory to peripherally directed therapies. Nociplastic pain is also associated with hypersensitivity to painful and other sensory stimuli (such as visual). Non‐painful sensory measures have not been well studied in nociceptive pain conditions nor directly compared to traditional pain sensitivity measures for their discriminative value. The current study aimed to investigate visual sensitivity across multiple chronic pain conditions, particularly in the context of analgesic treatment responsivity. Methods We compared sensitivity to experimental visual stimulation among individuals with chronic nociceptive pain, including hip osteoarthritis, chronic pelvic pain, rheumatoid arthritis, and psoriatic arthritis. Individuals with fibromyalgia, the prototypical nociplastic condition, and pain‐free controls were included for reference. Lack of analgesic response six months after surgery in osteoarthritis and chronic pelvic pain participants served as a model for nociplastic pain. Results Participants across all pain conditions reported greater perceived brightness in response to visual stimulation compared to controls. Higher self‐reported fibromyalgia symptom severity predicted lack of response to arthroplasty and hysterectomy. Notably, increased visual sensitivity independently predicted non‐responsiveness to surgery, whereas experimental pressure pain sensitivity did not. Visual sensitivity and fibromyalgia symptom severity together predicted greater variance in responder status than either measure alone. Conclusion These findings emphasize the potential value of assessing visual sensitivity to identify pain mechanisms across different diagnostic categories.
{"title":"Visual hypersensitivity as a transdiagnostic marker of surgical pain response in arthritis and chronic pain syndromes","authors":"Noah Waller, Steven E Harte, Richard E Harris, Andrew Schrepf, Tristin Smith, Eric Ichesco, Chelsea Kaplan, Flavia Sunzini, Deeba Minhas, Wendy Marder, Sara R Till, David A Williams, Chad M Brummett, Neil Basu, Sawsan As‐Sanie, Daniel J Clauw","doi":"10.1002/art.70042","DOIUrl":"https://doi.org/10.1002/art.70042","url":null,"abstract":"Objective Nociplastic pain is pain primarily driven by the central nervous system and, unlike nociceptive pain conditions, is thought to be refractory to peripherally directed therapies. Nociplastic pain is also associated with hypersensitivity to painful and other sensory stimuli (such as visual). Non‐painful sensory measures have not been well studied in nociceptive pain conditions nor directly compared to traditional pain sensitivity measures for their discriminative value. The current study aimed to investigate visual sensitivity across multiple chronic pain conditions, particularly in the context of analgesic treatment responsivity. Methods We compared sensitivity to experimental visual stimulation among individuals with chronic nociceptive pain, including hip osteoarthritis, chronic pelvic pain, rheumatoid arthritis, and psoriatic arthritis. Individuals with fibromyalgia, the prototypical nociplastic condition, and pain‐free controls were included for reference. Lack of analgesic response six months after surgery in osteoarthritis and chronic pelvic pain participants served as a model for nociplastic pain. Results Participants across all pain conditions reported greater perceived brightness in response to visual stimulation compared to controls. Higher self‐reported fibromyalgia symptom severity predicted lack of response to arthroplasty and hysterectomy. Notably, increased visual sensitivity independently predicted non‐responsiveness to surgery, whereas experimental pressure pain sensitivity did not. Visual sensitivity and fibromyalgia symptom severity together predicted greater variance in responder status than either measure alone. Conclusion These findings emphasize the potential value of assessing visual sensitivity to identify pain mechanisms across different diagnostic categories.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"22 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830295","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}
Taijie Jin, Jialin Dai, Chenlu Liu, Renkui Bai, Rachel Eisenberg, Yusha Wang, Jiahui Zhang, Wei Yin, Katrina Allis, Lindsay B. Henderson, Michelle Morrow, Natalie T. Deuitch, Pui Y. Lee, Daniel L. Kastner, Xiaomin Yu, Qing Zhou
Objectives This study first identified the biallelic loss‐of‐function variant in AP1M2 as the cause of autoinflammatory disease with colitis and aimed to elucidate the pathogenesis of AP1M2 deficiency in mice and humans. Methods We collected blood sample and sera from patient for genetic diagnosis and determination of inflammatory cytokines, respectively. Ap1m2 ‐deficient mice on the C57BL/6 background and DLD‐1 cells were used to dissect the functional role of Ap1m2 in serum and intestines. Stereo‐seq was performed on Ap1m2–/ – or Ap1m2–/ – :: Tnfr1–/– mouse samples to investigate the regulatory role of Tnfrl signaling in the pathogenesis of Ap1m2 deficiency‐caused intestinal inflammation. Super‐revolution imaging and CCVs enrichment were used to explore the molecular mechanism by which AP1M2 suppresses NF‐κB activation and chemokine production. Results Ap1m2–/– mice exhibited elevated chemokine production in serum and spontaneously developed intestinal inflammation, which phenocopies the patient with AP1M2 variant. Mechanistically, the deficiency of intestinal epithelial specific AP1M2 expression resulted in accumulation of TNFR1 signaling downstream proteins, including RIPK1, TBK1, IKKα/β and ΝΕΜΟ, leading to enhanced NF‐κB activation and subsequent chemokine overproduction. Tnfr1 knockout rescued gastrointestinal inflammation induced by Ap1m2 deficiency through suppressing NF‐κB activation and chemokine production. Conclusion This study identifies the deficiency of AP1M2 as the cause of a new autoinflammatory disease with colitis, and highlights the critical function of AP‐1 in suppressing NF‐κB activation and chemokine production. image
{"title":"Deficiency of AP1M2 causes a new autoinflammatory disease with colitis","authors":"Taijie Jin, Jialin Dai, Chenlu Liu, Renkui Bai, Rachel Eisenberg, Yusha Wang, Jiahui Zhang, Wei Yin, Katrina Allis, Lindsay B. Henderson, Michelle Morrow, Natalie T. Deuitch, Pui Y. Lee, Daniel L. Kastner, Xiaomin Yu, Qing Zhou","doi":"10.1002/art.70038","DOIUrl":"https://doi.org/10.1002/art.70038","url":null,"abstract":"Objectives This study first identified the biallelic loss‐of‐function variant in <jats:italic>AP1M2</jats:italic> as the cause of autoinflammatory disease with colitis and aimed to elucidate the pathogenesis of <jats:italic>AP1M2</jats:italic> deficiency in mice and humans. Methods We collected blood sample and sera from patient for genetic diagnosis and determination of inflammatory cytokines, respectively. <jats:italic>Ap1m2</jats:italic> ‐deficient mice on the C57BL/6 background and DLD‐1 cells were used to dissect the functional role of Ap1m2 in serum and intestines. Stereo‐seq was performed on <jats:italic>Ap1m2</jats:italic> <jats:sup> <jats:italic>–/</jats:italic> – </jats:sup> or <jats:italic>Ap1m2</jats:italic> <jats:sup> <jats:italic>–/</jats:italic> – </jats:sup> :: <jats:italic>Tnfr1</jats:italic> <jats:sup> <jats:italic>–/–</jats:italic> </jats:sup> mouse samples to investigate the regulatory role of Tnfrl signaling in the pathogenesis of Ap1m2 deficiency‐caused intestinal inflammation. Super‐revolution imaging and CCVs enrichment were used to explore the molecular mechanism by which AP1M2 suppresses NF‐κB activation and chemokine production. Results <jats:italic>Ap1m2</jats:italic> <jats:sup> <jats:italic>–/–</jats:italic> </jats:sup> mice exhibited elevated chemokine production in serum and spontaneously developed intestinal inflammation, which phenocopies the patient with <jats:italic>AP1M2</jats:italic> variant. Mechanistically, the deficiency of intestinal epithelial specific <jats:italic>AP1M2</jats:italic> expression resulted in accumulation of TNFR1 signaling downstream proteins, including RIPK1, TBK1, IKKα/β and ΝΕΜΟ, leading to enhanced NF‐κB activation and subsequent chemokine overproduction. <jats:italic>Tnfr1</jats:italic> knockout rescued gastrointestinal inflammation induced by <jats:italic>Ap1m2</jats:italic> deficiency through suppressing NF‐κB activation and chemokine production. Conclusion This study identifies the deficiency of <jats:italic>AP1M2</jats:italic> as the cause of a new autoinflammatory disease with colitis, and highlights the critical function of AP‐1 in suppressing NF‐κB activation and chemokine production. <jats:boxed-text content-type=\"graphic\" position=\"anchor\"> <jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/art70038-toc-0001-m.png\"> <jats:alt-text>image</jats:alt-text> </jats:graphic> </jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"25 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830294","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}
Morgan B. Downes, Sonia B. Nambadan, Joanne Chow, Ainsley R. Davies, Gemma Hart, Thomas D. Andrews, Nicole Lehmann, Isabella Bales, Alamelu Vengatasalam, Arthur Richard Kitching, Carolyn Hawkins, Ted Tsai, Chandima Perera, Giles Walters, Vicki Athanasopoulos, Simon Jiang
Objective Phenotypic diversity of autoimmune diseases presents an ongoing diagnostic and therapeutic challenge. The discovery of mutations in RELA (encoding RELA/p65) in patients with diverse disease phenotypes suggests heterogeneous pathophysiologic mechanisms are at play which may explain the observed phenotypic diversity. We identified seven novel/rare RELA variants in patients with autoimmune diseases and examined the functional consequences on immune signalling. Methods Whole exome sequencing analysis (WES) revealed seven novel/rare RELA variants. Following ectopic expression of wild type (WT) and mutant (MT) RELA proteins in HEK293 cells, NF‐ κ B/interferon‐β (IFNβ) luciferase reporter assays were used to determine transcriptional activity. RELA expression was also assessed in transfected HEK293 cells and in patient PBMCs (peripheral blood mononuclear cells) via western blot. NF‐ κ B and interferon stimulated genes (ISGs) in patient PBMCs were assessed via qPCR following toll‐like receptor (TLR) activation. Results RELA I250V , RELA R295H and RELA E3* displayed a loss in NF‐κB transcriptional activity. RELA I250V and RELA R295H induced hyperactivation of the IFNβ promoter. Comparative to RELA WT , ectopically expressed RELA I250V protein levels were reduced. Collectively, an elevated IFN gene signature was not detected in patient PBMCs following TLR activation, however the patient heterozygous for I250V had elevated IFNβ transcripts after TLR7/8 activation. Conclusion We expand upon the clinical syndromes linked to RELA dysfunction and uncover rare/novel variants that have distinct functional effects on gene transcription downstream of NF‐κB and IFNβ promoter elements. These findings reinforce an important role for RELA in a range of autoimmune and autoinflammatory diseases.
{"title":"Rare and Novel RELA Variants Contribute to Systemic Autoimmunity","authors":"Morgan B. Downes, Sonia B. Nambadan, Joanne Chow, Ainsley R. Davies, Gemma Hart, Thomas D. Andrews, Nicole Lehmann, Isabella Bales, Alamelu Vengatasalam, Arthur Richard Kitching, Carolyn Hawkins, Ted Tsai, Chandima Perera, Giles Walters, Vicki Athanasopoulos, Simon Jiang","doi":"10.1002/art.70046","DOIUrl":"https://doi.org/10.1002/art.70046","url":null,"abstract":"Objective Phenotypic diversity of autoimmune diseases presents an ongoing diagnostic and therapeutic challenge. The discovery of mutations in <jats:italic>RELA</jats:italic> (encoding RELA/p65) in patients with diverse disease phenotypes suggests heterogeneous pathophysiologic mechanisms are at play which may explain the observed phenotypic diversity. We identified seven novel/rare <jats:italic>RELA</jats:italic> variants in patients with autoimmune diseases and examined the functional consequences on immune signalling. Methods Whole exome sequencing analysis (WES) revealed seven novel/rare <jats:italic>RELA</jats:italic> variants. Following ectopic expression of wild type (WT) and mutant (MT) RELA proteins in HEK293 cells, NF‐ <jats:sc>κ</jats:sc> B/interferon‐β (IFNβ) luciferase reporter assays were used to determine transcriptional activity. RELA expression was also assessed in transfected HEK293 cells and in patient PBMCs (peripheral blood mononuclear cells) via western blot. NF‐ <jats:sc>κ</jats:sc> B and interferon stimulated genes (ISGs) in patient PBMCs were assessed via qPCR following toll‐like receptor (TLR) activation. Results RELA <jats:sup>I250V</jats:sup> , RELA <jats:sup>R295H</jats:sup> and RELA <jats:sup>E3*</jats:sup> displayed a loss in NF‐κB transcriptional activity. RELA <jats:sup>I250V</jats:sup> and RELA <jats:sup>R295H</jats:sup> induced hyperactivation of the <jats:italic>IFNβ</jats:italic> promoter. Comparative to RELA <jats:sup>WT</jats:sup> , ectopically expressed RELA <jats:sup>I250V</jats:sup> protein levels were reduced. Collectively, an elevated IFN gene signature was not detected in patient PBMCs following TLR activation, however the patient heterozygous for I250V had elevated <jats:italic>IFNβ</jats:italic> transcripts after TLR7/8 activation. Conclusion We expand upon the clinical syndromes linked to RELA dysfunction and uncover rare/novel variants that have distinct functional effects on gene transcription downstream of <jats:italic>NF‐κB</jats:italic> and <jats:italic>IFNβ</jats:italic> promoter elements. These findings reinforce an important role for RELA in a range of autoimmune and autoinflammatory diseases.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830296","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}
Jiatian Li, Jing Ye, Tuo Yang, David J. Hunter, Weiya Zhang, Michael Doherty, Yuqing Zhang, Zidan Yang, Hui Li, Yilun Wang, Dongxing Xie, Ziying Wu, Wei Li, Zeqin Wen, Changjun Li, Kai Zhao, Chao Zeng, Guanghua Lei, Jie Wei
Objectives Although gut microbiome dysbiosis is associated with symptomatic hand OA (SHOA), the role of bile acids (BAs), key metabolites in host‐microbiota interactions, in SHOA pathogenesis remains unexplored. We investigated the association between plasma BA metabolism and SHOA. Methods The associations between plasma BAs and SHOA were examined in the Xiangya Osteoarthritis (XO) Study and validated in an independent cohort through logistic regression models. Gut microbiome data from a previous study conducted within the XO Study were integrated to explore associations between SHOA‐related gut microbes and key BAs. As an exploratory analysis, gene‐based meta‐analyses evaluated associations between genes encoding key BA receptors and hand OA. Results In the discovery cohort (n=1,359, mean age 63.1±9.0 years, 58.4% women, SHOA prevalence 5.2%, all participants being Asian), elevated levels of deoxycholic acid (DCA) species (odds ratio [OR]=1.75, 95% confidence interval [CI]:1.03–2.96) and DCA (OR=2.14, 95% CI:1.24–3.70) were positively associated with SHOA presence and severity. These associations were replicated in an independent cohort (n=142). Multi‐omics analyses revealed significant correlations of DCA species, DCA, and the DCA species/total BAs ratio with SHOA‐related gut microbes. DCA interacted with SHOA‐related gut microbes and was associated with SHOA. Gene‐based meta‐analyses identified significant associations between genes encoding the Farnesoid X receptor and the pregnane X receptor and hand OA. Conclusion Dysregulated BA metabolism, particularly elevated DCA levels, is associated with SHOA. The observation that DCA interacts with SHOA‐related gut microbes, together with genes encoding DCA receptors, may help guide future biologically and clinically relevant studies.
{"title":"Bile acids metabolism in symptomatic hand osteoarthritis","authors":"Jiatian Li, Jing Ye, Tuo Yang, David J. Hunter, Weiya Zhang, Michael Doherty, Yuqing Zhang, Zidan Yang, Hui Li, Yilun Wang, Dongxing Xie, Ziying Wu, Wei Li, Zeqin Wen, Changjun Li, Kai Zhao, Chao Zeng, Guanghua Lei, Jie Wei","doi":"10.1002/art.70048","DOIUrl":"https://doi.org/10.1002/art.70048","url":null,"abstract":"Objectives Although gut microbiome dysbiosis is associated with symptomatic hand OA (SHOA), the role of bile acids (BAs), key metabolites in host‐microbiota interactions, in SHOA pathogenesis remains unexplored. We investigated the association between plasma BA metabolism and SHOA. Methods The associations between plasma BAs and SHOA were examined in the Xiangya Osteoarthritis (XO) Study and validated in an independent cohort through logistic regression models. Gut microbiome data from a previous study conducted within the XO Study were integrated to explore associations between SHOA‐related gut microbes and key BAs. As an exploratory analysis, gene‐based meta‐analyses evaluated associations between genes encoding key BA receptors and hand OA. Results In the discovery cohort (n=1,359, mean age 63.1±9.0 years, 58.4% women, SHOA prevalence 5.2%, all participants being Asian), elevated levels of deoxycholic acid (DCA) species (odds ratio [OR]=1.75, 95% confidence interval [CI]:1.03–2.96) and DCA (OR=2.14, 95% CI:1.24–3.70) were positively associated with SHOA presence and severity. These associations were replicated in an independent cohort (n=142). Multi‐omics analyses revealed significant correlations of DCA species, DCA, and the DCA species/total BAs ratio with SHOA‐related gut microbes. DCA interacted with SHOA‐related gut microbes and was associated with SHOA. Gene‐based meta‐analyses identified significant associations between genes encoding the Farnesoid X receptor and the pregnane X receptor and hand OA. Conclusion Dysregulated BA metabolism, particularly elevated DCA levels, is associated with SHOA. The observation that DCA interacts with SHOA‐related gut microbes, together with genes encoding DCA receptors, may help guide future biologically and clinically relevant studies.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"8 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830298","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}
Objective We investigated TNF‐induced neuropilin‐2 (NRP2) in rheumatoid arthritis (RA) and focused on its role in inflammation and disease progression and its potential as a therapeutic target in fibroblast‐like synoviocytes (FLS). Methods Serum and synovial fluid (SF) samples were collected from healthy volunteers (serum, n=30), osteoarthritis (OA) patients (SF, n=20), and RA patients (serum, n=76; SF, n=21) for NRP2 quantification. Synovial tissues from OA (n=6) and RA (n=6) patients were obtained to analyze NRP2 expression and its clinical relevance. Systemic or conditional NRP2 knockout mice were generated, and disease severity was evaluated in serum‐transfer‐induced arthritis (STIA) models. RA‐FLS were transfected with NRP2‐specific siRNA to assess the effects on proliferation, apoptosis, and pro‐inflammatory cytokine secretion. Chromatin immunoprecipitation sequencing (ChIP‐seq) was performed to identify p65‐binding sites in the NRP2 locus. Results NRP2 levels in RA serum (n=76) were elevated and correlated with disease activity. TNF upregulated NRP2 expression in FLS via the transcription factor p65, and elevated NRP2, in turn, amplified local inflammation and tissue damage by increasing FLS proliferation and promoting the release of cytokines, chemokines, and matrix metalloproteinases (MMPs). Both systemic and conditional knockout of NRP2 alleviated joint inflammation and damage in STIA models. The inflammatory regulation mediated by NRP2 was derived primarily from FAPα + THY1 + subset within the synovial sublining layer. Conclusion TNF‐induced NRP2 drives inflammatory persistence in RA and serves as a promising diagnostic biomarker. Targeting the TNF‐p65‐NRP2 axis in FLS may offer a novel strategy for mitigating arthritis progression. image
{"title":"TNF ‐induced neuropilin‐2 in fibroblast‐like synoviocytes exacerbates rheumatoid arthritis","authors":"Ke Jin, Jingjing Ran, Yuxin Deng, Zhiyong Miao, Ling Wei, Ying Yang, Min Yang, Tong Li, Haitao Niu, Geng Yin, Qibing Xie","doi":"10.1002/art.70028","DOIUrl":"https://doi.org/10.1002/art.70028","url":null,"abstract":"Objective We investigated TNF‐induced neuropilin‐2 (NRP2) in rheumatoid arthritis (RA) and focused on its role in inflammation and disease progression and its potential as a therapeutic target in fibroblast‐like synoviocytes (FLS). Methods Serum and synovial fluid (SF) samples were collected from healthy volunteers (serum, n=30), osteoarthritis (OA) patients (SF, n=20), and RA patients (serum, n=76; SF, n=21) for NRP2 quantification. Synovial tissues from OA (n=6) and RA (n=6) patients were obtained to analyze NRP2 expression and its clinical relevance. Systemic or conditional NRP2 knockout mice were generated, and disease severity was evaluated in serum‐transfer‐induced arthritis (STIA) models. RA‐FLS were transfected with NRP2‐specific siRNA to assess the effects on proliferation, apoptosis, and pro‐inflammatory cytokine secretion. Chromatin immunoprecipitation sequencing (ChIP‐seq) was performed to identify p65‐binding sites in the NRP2 locus. Results NRP2 levels in RA serum (n=76) were elevated and correlated with disease activity. TNF upregulated NRP2 expression in FLS via the transcription factor p65, and elevated NRP2, in turn, amplified local inflammation and tissue damage by increasing FLS proliferation and promoting the release of cytokines, chemokines, and matrix metalloproteinases (MMPs). Both systemic and conditional knockout of NRP2 alleviated joint inflammation and damage in STIA models. The inflammatory regulation mediated by NRP2 was derived primarily from FAPα <jats:sup>+</jats:sup> THY1 <jats:sup>+</jats:sup> subset within the synovial sublining layer. Conclusion TNF‐induced NRP2 drives inflammatory persistence in RA and serves as a promising diagnostic biomarker. Targeting the TNF‐p65‐NRP2 axis in FLS may offer a novel strategy for mitigating arthritis progression. <jats:boxed-text content-type=\"graphic\" position=\"anchor\"> <jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/art70028-toc-0001-m.png\"> <jats:alt-text>image</jats:alt-text> </jats:graphic> </jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"18 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830297","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}
Objectives Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs, with childhood‐onset SLE (cSLE) typically presenting a more severe course and greater genetic risk than adult‐onset SLE. While DNA methylation plays a key role in lupus pathogenesis, the epigenetic landscape of cSLE remains understudied. This study aimed to investigate DNA methylation changes in cSLE. Methods A total of 64 cSLE patients and 47 healthy control DNA samples isolated from peripheral blood mononuclear cells (PBMCs), along with an independent validation cohort of 38 patient DNA samples from whole blood, were analyzed. DNA methylation was assessed using the Infinium MethylationEPIC v2.0 array. Methylation differences were tested via linear regression adjusting for age, sex, medication use, and cell composition. Clinical features were compared using chi‐square test or Fisher's exact test, and gene ontology enrichment was conducted. Results Differential methylation analysis revealed significant hypomethylation in interferon‐regulated genes (e.g., DTX3L , PARP9 , IFI44L , MX1 ), enriched in type I interferon‐related processes. Hypomethylation in genes linked to B cell activation and senescence correlated with higher SLEDAI scores. K‐means clustering identified three distinct methylation‐based cSLE subgroups, each enriched for different biological processes: cell adhesion/growth factor response (Cluster One), cell differentiation/fate (Cluster Two), and oxidative stress/Rap1 signaling (Cluster Three). Sex‐based analysis showed immune‐related hypomethylation in male patients, with almost 90% of these sites identified in PBMCs also replicating in an independent whole‐blood dataset. Conclusion cSLE displays distinct DNA methylation patterns associated with disease activity, molecular subgroups, and sex, underscoring the potential for epigenetically informed diagnostics and therapies. image
{"title":"DNA methylation profiling reveals distinct epigenetic clusters and suggests epigenetic patterns associated with sex and disease activity in childhood‐onset lupus","authors":"Desiré Casares‐Marfil, Gülşah Kavrul Kayaalp, Vafa Guliyeva, Özlem Akgün, Şeyma Türkmen, Elif Kılıç Könte, Seher Şener, Sezgin Şahin, Özgür Kasapçopur, Betül Sözeri, Selçuk Sözer Tokdemir, Seza Özen, Nuray Aktay Ayaz, Amr H Sawalha","doi":"10.1002/art.70045","DOIUrl":"https://doi.org/10.1002/art.70045","url":null,"abstract":"Objectives Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs, with childhood‐onset SLE (cSLE) typically presenting a more severe course and greater genetic risk than adult‐onset SLE. While DNA methylation plays a key role in lupus pathogenesis, the epigenetic landscape of cSLE remains understudied. This study aimed to investigate DNA methylation changes in cSLE. Methods A total of 64 cSLE patients and 47 healthy control DNA samples isolated from peripheral blood mononuclear cells (PBMCs), along with an independent validation cohort of 38 patient DNA samples from whole blood, were analyzed. DNA methylation was assessed using the Infinium MethylationEPIC v2.0 array. Methylation differences were tested via linear regression adjusting for age, sex, medication use, and cell composition. Clinical features were compared using chi‐square test or Fisher's exact test, and gene ontology enrichment was conducted. Results Differential methylation analysis revealed significant hypomethylation in interferon‐regulated genes (e.g., <jats:italic>DTX3L</jats:italic> , <jats:italic>PARP9</jats:italic> , <jats:italic>IFI44L</jats:italic> , <jats:italic>MX1</jats:italic> ), enriched in type I interferon‐related processes. Hypomethylation in genes linked to B cell activation and senescence correlated with higher SLEDAI scores. K‐means clustering identified three distinct methylation‐based cSLE subgroups, each enriched for different biological processes: cell adhesion/growth factor response (Cluster One), cell differentiation/fate (Cluster Two), and oxidative stress/Rap1 signaling (Cluster Three). Sex‐based analysis showed immune‐related hypomethylation in male patients, with almost 90% of these sites identified in PBMCs also replicating in an independent whole‐blood dataset. Conclusion cSLE displays distinct DNA methylation patterns associated with disease activity, molecular subgroups, and sex, underscoring the potential for epigenetically informed diagnostics and therapies. <jats:boxed-text content-type=\"graphic\" position=\"anchor\"> <jats:graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" mimetype=\"image/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic/art70045-toc-0001-m.png\"> <jats:alt-text>image</jats:alt-text> </jats:graphic> </jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"56 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830300","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}
INTRODUCTIONSystemic sclerosis (SSc) is an autoimmune disease characterized by autoantibody production, fibrosis, and vasculopathy. The coexistence of ANCA-associated vasculitides (AAV) in SSc is rare and poorly characterized, with limited data on the impact of treatments, particularly high-dose glucocorticoids (GCs), on both conditions. This study aimed to describe the clinical phenotype, management, and outcomes of patients with overlapping SSc and AAV.METHODSWe conducted a multicenter retrospective study in 18 French centers, including patients who met the 2013 ACR/EULAR criteria for SSc and the 2022 ACR/EULAR criteria for AAV. Clinical, biologic, and radiologic data were collected.RESULTSWe included 30 patients (median age 51.5 years, 83% female). SSc preceded AAV in all cases; 27% had diffuse cutaneous SSc, while 73% had limited cutaneous SSc. Anti-Scl70 antibodies were detected in 50%, and interstitial lung disease (ILD) was present in 80%, predominantly with a fibrosing non-specific interstitial pneumonia pattern (54%). AAV was microscopic polyangiitis in 90%, with MPO-ANCA positivity in 93%. Renal involvement was common (76%), with a median serum creatinine of 170 μmol/l (IQR 120-361) and proteinuria of 2 g/g (IQR 0.9-2.3). All patients received GCs in combination with cyclophosphamide (50%) or rituximab (47%). No cases of scleroderma renal crisis were observed. SSc manifestations, including ILD and skin involvement, remained stable during follow-up.CONCLUSIONAAV, predominantly microscopic polyangiitis with MPO-ANCA, can occur in SSc, particularly in patients with fibrosing ILD and anti-Scl70. Standard vasculitis treatments appear to be effective and do not worsen outcomes in SSc.
{"title":"ANCA-Associated Vasculitides in Systemic Sclerosis: A Unique Clinical Overlap with Significant Implications for Treatment and Outcomes.","authors":"Deborah Eshagh,Thomas Quéméneur,Alexandre Karras,Viviane Queyrel,Jean-Francois Augusto,Christian Agard,Vincent Audard,Alexandre Cez,Marion Couderc,Pierre Duffau,Cécile Audrey Durel,Stanislas Faguer,Noémie Jourde-Chiche,Aurélie Lavergne,Christian Lavigne,Nicolas Limal,Rafik Mesbah,Amélie Servettaz,Carole Philipponnet,Perrine Smets,Theophile Hubsch,Benjamin Chaigne,Alexis Régent,Xavier Puéchal,Luc Mouthon,Benjamin Terrier, ","doi":"10.1002/art.70032","DOIUrl":"https://doi.org/10.1002/art.70032","url":null,"abstract":"INTRODUCTIONSystemic sclerosis (SSc) is an autoimmune disease characterized by autoantibody production, fibrosis, and vasculopathy. The coexistence of ANCA-associated vasculitides (AAV) in SSc is rare and poorly characterized, with limited data on the impact of treatments, particularly high-dose glucocorticoids (GCs), on both conditions. This study aimed to describe the clinical phenotype, management, and outcomes of patients with overlapping SSc and AAV.METHODSWe conducted a multicenter retrospective study in 18 French centers, including patients who met the 2013 ACR/EULAR criteria for SSc and the 2022 ACR/EULAR criteria for AAV. Clinical, biologic, and radiologic data were collected.RESULTSWe included 30 patients (median age 51.5 years, 83% female). SSc preceded AAV in all cases; 27% had diffuse cutaneous SSc, while 73% had limited cutaneous SSc. Anti-Scl70 antibodies were detected in 50%, and interstitial lung disease (ILD) was present in 80%, predominantly with a fibrosing non-specific interstitial pneumonia pattern (54%). AAV was microscopic polyangiitis in 90%, with MPO-ANCA positivity in 93%. Renal involvement was common (76%), with a median serum creatinine of 170 μmol/l (IQR 120-361) and proteinuria of 2 g/g (IQR 0.9-2.3). All patients received GCs in combination with cyclophosphamide (50%) or rituximab (47%). No cases of scleroderma renal crisis were observed. SSc manifestations, including ILD and skin involvement, remained stable during follow-up.CONCLUSIONAAV, predominantly microscopic polyangiitis with MPO-ANCA, can occur in SSc, particularly in patients with fibrosing ILD and anti-Scl70. Standard vasculitis treatments appear to be effective and do not worsen outcomes in SSc.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"33 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830345","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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