Jayne M MacMahon,Angelo Ravelli,Ana Isabel Rebollo-Giménez,Valentina Natoli,Chiara Campone,Francesca Bovis,Tomo Nozawa,Y Ingrid Goh,Alessandro Consolaro,Brian M Feldman,Silvia Rosina
INTRODUCTIONJuvenile dermatomyositis (JDM) is a rare autoimmune condition. The treat-to-target (T2T) strategy has garnered interest in paediatric rheumatology. It is based on defining clear therapeutic targets, with frequent disease activity monitoring, and adjustment of the treatments if targets are not met within a defined time frame. Recently, an international Task Force of experts launched an initiative aimed at the development of recommendations for the adoption of T2T strategy in JDM. This study was done to support those recommendations.OBJECTIVESWe aimed to determine the time to treatment response in patients with JDM, to better inform the development of a T2T strategy in JDM.METHODSThis is a retrospective review of patients with a physician-confirmed diagnosis of JDM, followed at two tertiary care centres-the IRCCS Istituto Giannina Gaslini (Gaslini), and The Hospital for Sick Children (SickKids). Demographic and clinical data were obtained on all patients with JDM during the first two years following diagnosis. Kaplan-Meier survival curves were used to determine time to outcome definitions.RESULTS187 patients were identified across two sites; the mean age of diagnosis was 8 years. On average, patients with JDM achieved normalization of muscle enzymes and muscle remission 3 and 6 months after treatment initiation, respectively. Skin remission occurred within 12 months after starting treatment. Time to reach inactive disease varied between the sites, with median time 10.3 months (Gaslini) and 8.8 months (SickKids).CONCLUSIONSThis study provides real-world data for potential timelines to target with a T2T strategy for JDM.
{"title":"Toward a treat-to-target strategy in juvenile dermatomyositis: what are the suitable targets and optimal timing of their achievement?","authors":"Jayne M MacMahon,Angelo Ravelli,Ana Isabel Rebollo-Giménez,Valentina Natoli,Chiara Campone,Francesca Bovis,Tomo Nozawa,Y Ingrid Goh,Alessandro Consolaro,Brian M Feldman,Silvia Rosina","doi":"10.1002/art.43431","DOIUrl":"https://doi.org/10.1002/art.43431","url":null,"abstract":"INTRODUCTIONJuvenile dermatomyositis (JDM) is a rare autoimmune condition. The treat-to-target (T2T) strategy has garnered interest in paediatric rheumatology. It is based on defining clear therapeutic targets, with frequent disease activity monitoring, and adjustment of the treatments if targets are not met within a defined time frame. Recently, an international Task Force of experts launched an initiative aimed at the development of recommendations for the adoption of T2T strategy in JDM. This study was done to support those recommendations.OBJECTIVESWe aimed to determine the time to treatment response in patients with JDM, to better inform the development of a T2T strategy in JDM.METHODSThis is a retrospective review of patients with a physician-confirmed diagnosis of JDM, followed at two tertiary care centres-the IRCCS Istituto Giannina Gaslini (Gaslini), and The Hospital for Sick Children (SickKids). Demographic and clinical data were obtained on all patients with JDM during the first two years following diagnosis. Kaplan-Meier survival curves were used to determine time to outcome definitions.RESULTS187 patients were identified across two sites; the mean age of diagnosis was 8 years. On average, patients with JDM achieved normalization of muscle enzymes and muscle remission 3 and 6 months after treatment initiation, respectively. Skin remission occurred within 12 months after starting treatment. Time to reach inactive disease varied between the sites, with median time 10.3 months (Gaslini) and 8.8 months (SickKids).CONCLUSIONSThis study provides real-world data for potential timelines to target with a T2T strategy for JDM.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"28 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477452","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}
Liang Wu,Qiuping Zhang,Zhigang Tang,Yanhong Li,Tong Wu,Lvyi Chen,Chunyu Tan,Lingshu Zhang,Xing Ji,Sijun Zhang,Yinlan Wu,Aline Bozec,Mario M Zaiss,Yubin Luo
OBJECTIVETo investigate the specific role of tryptophan metabolism, especially that of microbiome-derived metabolites, in the development of rheumatoid arthritis (RA).METHODSWe employed metabolomics to profile metabolites in 53 high-risk for RA individuals (PreRAs), 30 established RA patients and 38 healthy individuals. Fecal microbiota transplantation (FMT) and collagen-induced arthritis (CIA) mouse models were used to investigate the impact of gut microbiome on arthritis severity, gut barrier function, and metabolic change. Treg cell differentiation and epithelial cells' barrier function were assessed by flow cytometry, immunofluoresence staining and western blotting. Co-immunoprecipitation and luciferase were applied for molecular mechanism studies.RESULTSDysregulated tryptophan metabolism exists in RA and PreRA individuals, as well as in FMT mice, characterized by a shift toward the kynurenine pathway and reduced activity of serotonin and indole pathways. Indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) significantly alleviated arthritis in CIA mice by expanding Treg cells via the classical aryl hydrocarbon receptor (AhR)-aryl hydrocarbon receptor nuclear translocator (ARNT)-xenobiotic response element (XRE) signaling pathway. Moreover, ILA repaired the leaking gut by increasing Zo-1 and occludin expression in Caco-2 cells, which was blocked by AhR antagonist CH223191. Moreover, CH223191 treatment could significantly reverse the improving effects of ILA and IAA on arthritis in mice.CONCLUSIONThese findings indicate that Trp indole metabolites may play a negative regulatory role in the progression of RA by affecting Treg cell development and intestinal gut barrier function.
{"title":"Gut microbiota-derived tryptophan indole metabolites ameliorate collagen-induced arthritis in mice via aryl hydrocarbon receptor activation in T cells and intestinal epithelial cells.","authors":"Liang Wu,Qiuping Zhang,Zhigang Tang,Yanhong Li,Tong Wu,Lvyi Chen,Chunyu Tan,Lingshu Zhang,Xing Ji,Sijun Zhang,Yinlan Wu,Aline Bozec,Mario M Zaiss,Yubin Luo","doi":"10.1002/art.43430","DOIUrl":"https://doi.org/10.1002/art.43430","url":null,"abstract":"OBJECTIVETo investigate the specific role of tryptophan metabolism, especially that of microbiome-derived metabolites, in the development of rheumatoid arthritis (RA).METHODSWe employed metabolomics to profile metabolites in 53 high-risk for RA individuals (PreRAs), 30 established RA patients and 38 healthy individuals. Fecal microbiota transplantation (FMT) and collagen-induced arthritis (CIA) mouse models were used to investigate the impact of gut microbiome on arthritis severity, gut barrier function, and metabolic change. Treg cell differentiation and epithelial cells' barrier function were assessed by flow cytometry, immunofluoresence staining and western blotting. Co-immunoprecipitation and luciferase were applied for molecular mechanism studies.RESULTSDysregulated tryptophan metabolism exists in RA and PreRA individuals, as well as in FMT mice, characterized by a shift toward the kynurenine pathway and reduced activity of serotonin and indole pathways. Indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) significantly alleviated arthritis in CIA mice by expanding Treg cells via the classical aryl hydrocarbon receptor (AhR)-aryl hydrocarbon receptor nuclear translocator (ARNT)-xenobiotic response element (XRE) signaling pathway. Moreover, ILA repaired the leaking gut by increasing Zo-1 and occludin expression in Caco-2 cells, which was blocked by AhR antagonist CH223191. Moreover, CH223191 treatment could significantly reverse the improving effects of ILA and IAA on arthritis in mice.CONCLUSIONThese findings indicate that Trp indole metabolites may play a negative regulatory role in the progression of RA by affecting Treg cell development and intestinal gut barrier function.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"40 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477419","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}
Hideaki Tsuji,Fabricio Espinosa-Ortega,Irene Peralta Garcia,Maryam Dastmalchi,Ingrid E Lundberg,Karin Lodin
OBJECTIVESOur aim was to explore maintenance of glucocorticoid-free remission in patients with idiopathic inflammatory myopathy (IIM). Secondary, we examined the performance of the International Myositis Assessment and Clinical Study Group (IMACS) criteria for complete clinical response and flare/worsening.METHODSPatients achieving physician-determined glucocorticoid-free remission were extracted from the Swedish Rheumatology Quality Register (SRQ). Relapse rates and associated factors were analyzed. To assess the performance of complete clinical response criteria, IMACS core set measures were evaluated within 6 months before and after remission. Relapse was defined as IMACS criteria of worsening in IMACS core set measures over 20-30% during every visit, or in the period from remission to a time point with worsening (modified definition), or glucocorticoid/immunosuppressant administration. Changes from remission to all subsequent visits were compared. The visit with the largest change was chosen as the worse time-point (modified definition).RESULTSOf 494 patients, 159 (32%) achieved physician-determined glucocorticoid-free remission. The 12-year cumulative relapse rate was 76%, with anti-Jo1 as a risk factor. From time of remission to 6 months after remission, IMACS complete clinical response fulfillment rates were: CK 23%, HAQ 50%, patient-global assessment 70%, physician-global assessment 80%, extra-muscular activity 83%, MMT8 95%. Only 50% of relapses could be captured by IMACS-worsening definition, but additional relapses were captured by a modified IMACS-worsening definition (15%) or by re-introduction of glucocorticoid/immunosuppressant treatment (35%).CONCLUSIONRelapses were frequent in IIM patients after achieving glucocorticoid-free remission and required management of therapy. IMACS criteria for complete clinical response/worsening need to be amended.
目的探讨特发性炎性肌病（IIM）患者无糖皮质激素缓解的维持情况。其次，我们检查了国际肌炎评估和临床研究组（IMACS）完全临床反应和发作/恶化标准的表现。方法从瑞典风湿病质量登记（SRQ）中提取获得医生确定的无糖皮质激素缓解的患者。分析复发率及相关因素。为了评估完整临床反应标准的表现，在缓解前后6个月内评估IMACS核心组措施。复发定义为每次就诊时IMACS核心组测量值超过20-30%恶化的IMACS标准，或从缓解期到恶化的时间点（修改定义），或糖皮质激素/免疫抑制剂给药。比较了从缓解到所有后续访问的变化。选择变化最大的访问作为最差时间点（修改定义）。结果494例患者中，159例（32%）达到医生确定的无糖皮质激素缓解。12年累计复发率为76%，抗jo1为危险因素。从缓解时间到缓解后6个月，IMACS完全临床反应满意率为：CK 23%， HAQ 50%，患者整体评估70%，医生整体评估80%，肌肉外活动83%，MMT8 95%。只有50%的复发可被imacs恶化定义捕获，但通过修改imacs恶化定义（15%）或重新引入糖皮质激素/免疫抑制剂治疗（35%）捕获了额外的复发。结论IIM患者在达到无糖皮质激素缓解并需要适当治疗后，复发较为频繁。IMACS关于完全临床缓解/恶化的标准需要修订。
{"title":"Relapse Rate After Glucocorticoid-free Remission in patients with Idiopathic Inflammatory Myopathies and Validation of the International Myositis Assessment and Clinical Studies Group (IMACS) Criteria for Complete Clinical Response and Worsening.","authors":"Hideaki Tsuji,Fabricio Espinosa-Ortega,Irene Peralta Garcia,Maryam Dastmalchi,Ingrid E Lundberg,Karin Lodin","doi":"10.1002/art.43429","DOIUrl":"https://doi.org/10.1002/art.43429","url":null,"abstract":"OBJECTIVESOur aim was to explore maintenance of glucocorticoid-free remission in patients with idiopathic inflammatory myopathy (IIM). Secondary, we examined the performance of the International Myositis Assessment and Clinical Study Group (IMACS) criteria for complete clinical response and flare/worsening.METHODSPatients achieving physician-determined glucocorticoid-free remission were extracted from the Swedish Rheumatology Quality Register (SRQ). Relapse rates and associated factors were analyzed. To assess the performance of complete clinical response criteria, IMACS core set measures were evaluated within 6 months before and after remission. Relapse was defined as IMACS criteria of worsening in IMACS core set measures over 20-30% during every visit, or in the period from remission to a time point with worsening (modified definition), or glucocorticoid/immunosuppressant administration. Changes from remission to all subsequent visits were compared. The visit with the largest change was chosen as the worse time-point (modified definition).RESULTSOf 494 patients, 159 (32%) achieved physician-determined glucocorticoid-free remission. The 12-year cumulative relapse rate was 76%, with anti-Jo1 as a risk factor. From time of remission to 6 months after remission, IMACS complete clinical response fulfillment rates were: CK 23%, HAQ 50%, patient-global assessment 70%, physician-global assessment 80%, extra-muscular activity 83%, MMT8 95%. Only 50% of relapses could be captured by IMACS-worsening definition, but additional relapses were captured by a modified IMACS-worsening definition (15%) or by re-introduction of glucocorticoid/immunosuppressant treatment (35%).CONCLUSIONRelapses were frequent in IIM patients after achieving glucocorticoid-free remission and required management of therapy. IMACS criteria for complete clinical response/worsening need to be amended.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"6 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477420","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}
Lisa R. Sammaritano, Anca Askanase, Bonnie L. Bermas, Maria Dall'Era, Alí Duarte-García, Linda T. Hiraki, Mary Beth F. Son, Victoria P. Werth, Cynthia Aranow, April Barnado, Anna Broder, Hermine I. Brunner, Benjamin F. Chong, Vaidehi R. Chowdhary, Aimee O. Hersh, Peter M. Izmirly, Marimee Jules, Kenneth Kalunian, Diane Kamen, Tamar B. Rubinstein, Benjamin J. Smith, Natalie M. Smith, Asha Thomas, Homa Timlin, Daniel J. Wallace, Muayad Azzam, Christie M. Bartels, Joanne S. Cunha, Kimberly DeQuattro, Andrea Fava, Gabriel Figueroa-Parra, Shivani Garg, Lais Lopes Almeida Gomes, Maria C. Cuéllar-Gutiérrez, Priyanka Iyer, Andrew S. Johannemann, April Jorge, Shanthini Kasturi, Hassan Kawtharany, Jana Khawandi, Alexandra Legge, Kimberly P. Liang, Megan M. Lockwood, Alain Sanchez-Rodriguez, Marat Turgunbaev, Jessica N. Williams, Amy S. Turner, Reem A. Mustafa
To provide evidence-based and expert guidance for the treatment and management of non-renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline.
{"title":"2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus","authors":"Lisa R. Sammaritano, Anca Askanase, Bonnie L. Bermas, Maria Dall'Era, Alí Duarte-García, Linda T. Hiraki, Mary Beth F. Son, Victoria P. Werth, Cynthia Aranow, April Barnado, Anna Broder, Hermine I. Brunner, Benjamin F. Chong, Vaidehi R. Chowdhary, Aimee O. Hersh, Peter M. Izmirly, Marimee Jules, Kenneth Kalunian, Diane Kamen, Tamar B. Rubinstein, Benjamin J. Smith, Natalie M. Smith, Asha Thomas, Homa Timlin, Daniel J. Wallace, Muayad Azzam, Christie M. Bartels, Joanne S. Cunha, Kimberly DeQuattro, Andrea Fava, Gabriel Figueroa-Parra, Shivani Garg, Lais Lopes Almeida Gomes, Maria C. Cuéllar-Gutiérrez, Priyanka Iyer, Andrew S. Johannemann, April Jorge, Shanthini Kasturi, Hassan Kawtharany, Jana Khawandi, Alexandra Legge, Kimberly P. Liang, Megan M. Lockwood, Alain Sanchez-Rodriguez, Marat Turgunbaev, Jessica N. Williams, Amy S. Turner, Reem A. Mustafa","doi":"10.1002/art.43452","DOIUrl":"https://doi.org/10.1002/art.43452","url":null,"abstract":"To provide evidence-based and expert guidance for the treatment and management of non-renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"84 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145434613","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}
Hermine I Brunner,Ekaterina Alexeeva,Marcia Bandeira,Ruy Carrasco,Jeffrey Chaitow,Peter Chiraseveenuprapund,Tracy V Ting,Muferet Erguven,Beth Gottlieb,Sheila Knupp Oliveira,Pooja N Patel,Seza Ozen,Claudia Saad Magalhaes,Inmaculada Calvo Penadés,David Gruben,Rebecca Germino,Holly B Posner,Lori Stockert,Alberto Martini,Daniel J Lovell,Nicolino Ruperto,
OBJECTIVEJuvenile idiopathic arthritis (JIA) is associated with impaired overall health-related quality of life (HRQoL). We evaluated the impact of tofacitinib on patient-reported outcomes (PROs) in patients with JIA.METHODSThis was a post hoc analysis of a phase III, randomized, double-blind, placebo-controlled withdrawal trial (NCT02592434) in patients with JIA. In the open-label phase (Part 1; weeks 0-18), patients received body weight-based doses of tofacitinib. During the double-blind phase (Part 2; weeks 18-44) responders (per JIA-American College of Rheumatology 30 response criteria) were randomized 1:1 to continue tofacitinib or switch to placebo for up to 26 weeks. Assessed PROs included the validated parent/legal guardian versions of the Childhood Health Assessment Questionnaire (CHAQ) for evaluation of disability, arthritis pain, overall well-being, and the Child Health Questionnaire (CHQ).RESULTSOverall, 225 patients were enrolled and received open-label tofacitinib in Part 1, and 173 were randomized in Part 2. During Part 1, least squares (LS) mean (standard error [SE]) disability, arthritis pain, and overall well-being scores numerically improved from 1.04 (0.05), 5.53 (0.20), and 5.07 (0.20) at baseline to 0.57 (0.05), 2.46 (0.18), and 2.47 (0.18) at week 18, respectively. LS mean (SE) CHQ physical summary and psychological summary scores numerically improved from 29.51 (1.15) and 47.24 (0.85) at baseline to 42.70 (0.98) and 51.53 (0.80) at week 18, respectively. Improvements were generally maintained to Week 44 in Part 2.CONCLUSIONTofacitinib improved a range of PROs in patients with JIA, suggesting potential HRQoL benefits.
目的：青少年特发性关节炎（JIA）与总体健康相关生活质量（HRQoL）受损相关。我们评估了托法替尼对JIA患者报告预后（pro）的影响。方法：这是一项针对JIA患者的III期、随机、双盲、安慰剂对照戒断试验（NCT02592434）的事后分析。在开放标签期（第1部分，0-18周），患者接受基于体重的托法替尼剂量。在双盲期（第2部分，18-44周），应答者（根据JIA-American College of Rheumatology的30个应答标准）按1:1随机分配，继续使用法西替尼或切换到安慰剂长达26周。评估的优点包括有效的父母/法定监护人版本的儿童健康评估问卷（CHAQ），用于评估残疾、关节炎疼痛、整体幸福感和儿童健康问卷（CHQ）。结果在第一部分中，225名患者入组并接受开放标签托法替尼治疗，在第二部分中，173名患者随机入组。在第一部分中，最小二乘（LS）平均（标准误差[SE]）残疾、关节炎疼痛和总体幸福感得分分别从基线时的1.04（0.05）、5.53（0.20）和5.07（0.20）改善到第18周时的0.57（0.05）、2.46（0.18）和2.47（0.18）。LS平均（SE） CHQ生理总结和心理总结得分分别从基线时的29.51（1.15）和47.24（0.85）提高到第18周时的42.70（0.98）和51.53（0.80）。第2部分的改进一般维持到第44周。结论托法替尼改善了JIA患者的一系列PROs，提示潜在的HRQoL益处。
{"title":"Tofacitinib for the Treatment of Juvenile Idiopathic Arthritis: Patient-Reported Outcomes in a Phase III, Randomized, Double-Blind, Placebo-Controlled Withdrawal Trial.","authors":"Hermine I Brunner,Ekaterina Alexeeva,Marcia Bandeira,Ruy Carrasco,Jeffrey Chaitow,Peter Chiraseveenuprapund,Tracy V Ting,Muferet Erguven,Beth Gottlieb,Sheila Knupp Oliveira,Pooja N Patel,Seza Ozen,Claudia Saad Magalhaes,Inmaculada Calvo Penadés,David Gruben,Rebecca Germino,Holly B Posner,Lori Stockert,Alberto Martini,Daniel J Lovell,Nicolino Ruperto, ","doi":"10.1002/art.43428","DOIUrl":"https://doi.org/10.1002/art.43428","url":null,"abstract":"OBJECTIVEJuvenile idiopathic arthritis (JIA) is associated with impaired overall health-related quality of life (HRQoL). We evaluated the impact of tofacitinib on patient-reported outcomes (PROs) in patients with JIA.METHODSThis was a post hoc analysis of a phase III, randomized, double-blind, placebo-controlled withdrawal trial (NCT02592434) in patients with JIA. In the open-label phase (Part 1; weeks 0-18), patients received body weight-based doses of tofacitinib. During the double-blind phase (Part 2; weeks 18-44) responders (per JIA-American College of Rheumatology 30 response criteria) were randomized 1:1 to continue tofacitinib or switch to placebo for up to 26 weeks. Assessed PROs included the validated parent/legal guardian versions of the Childhood Health Assessment Questionnaire (CHAQ) for evaluation of disability, arthritis pain, overall well-being, and the Child Health Questionnaire (CHQ).RESULTSOverall, 225 patients were enrolled and received open-label tofacitinib in Part 1, and 173 were randomized in Part 2. During Part 1, least squares (LS) mean (standard error [SE]) disability, arthritis pain, and overall well-being scores numerically improved from 1.04 (0.05), 5.53 (0.20), and 5.07 (0.20) at baseline to 0.57 (0.05), 2.46 (0.18), and 2.47 (0.18) at week 18, respectively. LS mean (SE) CHQ physical summary and psychological summary scores numerically improved from 29.51 (1.15) and 47.24 (0.85) at baseline to 42.70 (0.98) and 51.53 (0.80) at week 18, respectively. Improvements were generally maintained to Week 44 in Part 2.CONCLUSIONTofacitinib improved a range of PROs in patients with JIA, suggesting potential HRQoL benefits.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"83 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403859","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}
Valentina Querin, Leonardo Palazzo, Agnes B. Fogo, Mark Haas, David R. W. Jayne, Liz Lightstone, Brad H. Rovin, Surya V. Seshan, Augusto Vaglio, Ioannis Parodis, Ingeborg M. Bajema
Lupus nephritis (LN) is characterized by a variable disease course, necessitating continuous monitoring. There is an urgent need to identify non-invasive biomarkers. By reviewing and critically assessing the quality of existing studies on LN biomarkers correlating with histopathology, we here explore the challenges in promoting their use in clinical practice and identify promising candidates for future validation.
{"title":"Biomarkers of Lupus Nephritis Histopathology: Where Do We Stand?","authors":"Valentina Querin, Leonardo Palazzo, Agnes B. Fogo, Mark Haas, David R. W. Jayne, Liz Lightstone, Brad H. Rovin, Surya V. Seshan, Augusto Vaglio, Ioannis Parodis, Ingeborg M. Bajema","doi":"10.1002/art.43427","DOIUrl":"https://doi.org/10.1002/art.43427","url":null,"abstract":"Lupus nephritis (LN) is characterized by a variable disease course, necessitating continuous monitoring. There is an urgent need to identify non-invasive biomarkers. By reviewing and critically assessing the quality of existing studies on LN biomarkers correlating with histopathology, we here explore the challenges in promoting their use in clinical practice and identify promising candidates for future validation.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"16 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145404682","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}
S Janna Bashar,Courtney B Myhr,Adam H Titi,Zihao Zheng,Miriam A Shelef
OBJECTIVEAnti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) can be promiscuous, with cross-reactive binding to many antigens containing short motifs, or private with little cross-reactivity. Also, ACPA reactivity patterns differ among RA patients, including for motif-containing epitopes in important self-antigens like collagen and IgG (bound by RA-associated rheumatoid factors, RFs), with limited understanding of the underlying mechanism. The objective of this study was to determine if HLA alleles associate with ACPA reactivity patterns.METHODSFor 100 ACPA+RF+ RA participants, serum IgG binding was quantified by enzyme-linked immunosorbent assay to ten citrulline-containing peptides derived from type II collagen and IgG1 (nine with motifs), and HLA loci were genotyped. Also, antibody and serum multi-reactivity were evaluated. HLA alleles present differentially in RA participants with high versus low IgG binding to specific peptides as well as with multi-reactivity versus limited reactivity were identified by Fisher's exact test.RESULTSSerum IgG multi-reactivity for citrulline-glycine motif-containing collagen peptides was high, at least partially due to promiscuous antibodies. HLA-DQA1*01:02 was present in more participants with anti-citrullinated collagen antibodies and multi-reactive sera. In contrast, serum multi-reactivity was low for IgG1-derived peptides due at least in part to more private antibodies. Shared epitope-containing HLA-DRB1*04:01 was present more frequently in participants with RA-associated RFs irrespective of the citrulline-serine motif and less frequently in participants with anti-citrullinated collagen antibodies. Several HLA alleles associated with specific antibody reactivities.CONCLUSIONDifferent HLA alleles may contribute to the different reactivity patterns of promiscuous anti-citrullinated collagen antibodies and more private RA-associated RFs.
{"title":"HLA-DQA1*01:02 is associated with antibody multi-reactivity with citrulline-containing type II collagen epitopes while HLA-DRB1*04:01 is associated with more private antibody reactivity with citrulline-containing IgG epitopes in rheumatoid arthritis.","authors":"S Janna Bashar,Courtney B Myhr,Adam H Titi,Zihao Zheng,Miriam A Shelef","doi":"10.1002/art.43424","DOIUrl":"https://doi.org/10.1002/art.43424","url":null,"abstract":"OBJECTIVEAnti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) can be promiscuous, with cross-reactive binding to many antigens containing short motifs, or private with little cross-reactivity. Also, ACPA reactivity patterns differ among RA patients, including for motif-containing epitopes in important self-antigens like collagen and IgG (bound by RA-associated rheumatoid factors, RFs), with limited understanding of the underlying mechanism. The objective of this study was to determine if HLA alleles associate with ACPA reactivity patterns.METHODSFor 100 ACPA+RF+ RA participants, serum IgG binding was quantified by enzyme-linked immunosorbent assay to ten citrulline-containing peptides derived from type II collagen and IgG1 (nine with motifs), and HLA loci were genotyped. Also, antibody and serum multi-reactivity were evaluated. HLA alleles present differentially in RA participants with high versus low IgG binding to specific peptides as well as with multi-reactivity versus limited reactivity were identified by Fisher's exact test.RESULTSSerum IgG multi-reactivity for citrulline-glycine motif-containing collagen peptides was high, at least partially due to promiscuous antibodies. HLA-DQA1*01:02 was present in more participants with anti-citrullinated collagen antibodies and multi-reactive sera. In contrast, serum multi-reactivity was low for IgG1-derived peptides due at least in part to more private antibodies. Shared epitope-containing HLA-DRB1*04:01 was present more frequently in participants with RA-associated RFs irrespective of the citrulline-serine motif and less frequently in participants with anti-citrullinated collagen antibodies. Several HLA alleles associated with specific antibody reactivities.CONCLUSIONDifferent HLA alleles may contribute to the different reactivity patterns of promiscuous anti-citrullinated collagen antibodies and more private RA-associated RFs.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"27 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403862","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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