{"title":"letter to the Editor, Nociplasticity, rather than fibromyalgia, best conceptualizes symptoms not linked to well-defined organ disease in systemic lupus erythematosus: Comment on the article by Pisetsky, et al.","authors":"Don L Goldenberg","doi":"10.1002/art.43426","DOIUrl":"https://doi.org/10.1002/art.43426","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"54 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373768","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}
OBJECTIVEThe therapeutic effects of Telitacicept combined with standard of care (SoC) in childhood-onset systemic lupus erythematosus (cSLE) remain unclear. This study aims to evaluate its efficacy in comparison with Belimumab combined with SoC.METHODSWe performed a prospective cohort study across 7 tertiary hospitals in China, enrolling patients aged 5-18 with cSLE. Primary endpoints included the proportions of patients attaining Lupus Low Disease Activity State (LLDAS) and Doris at 3, 6, and 12 months after treatment, complemented by relapse rates and steroid tapering metrics. Propensity score-based inverse probability of treatment weighting (IPTW) was employed to address baseline imbalances between the Telitacicept (n=60) and the historical control group treated with Belimumab (n=67).RESULTSAmong 60 enrolled patients (median follow-up 12 [IQR 6-12] months), LLDAS/Doris achievement rates progressively increased from 19.6%/7.8% at 6months to 65.7%/37.1% at 12 months. Flare rates remained low (3-month: 1.7%; 6-month:11.8%; 12-month: 14.3%). Notably, 74.3% of patients achieved prednisone doses ≤7.5 mg/day by 12 months (vs. baseline 13.3%, P<0.0001). IPTW-adjusted analyses demonstrated comparable efficacy between the Telitacicept and Belimumab groups across all endpoints in terms of LLDAS/Doris attainment, steroid reduction, and immunological normalization (all P > 0.05).CONCLUSIONTelitacicept combined with SoC exhibited significant improvements in disease activity, steroid reduction, and immunological markers, with therapeutic outcomes comparable to Belimumab in cSLE management.
{"title":"The efficacy of Telitacicept in Childhood-onset Systemic Lupus Erythematosus: a prospective multi-center cohort study with IPTW-adjusted comparison to a historical control group treated with Belimumab.","authors":"Chong Luo,Shu Su,Jingyue Liu,Junyu Lin,Jin Song,Zongwen Chen,Yuanyuan Peng,Lijun Jiang,Meng Jia,Li Wang,Xinhui Jiang,Wei Zhang,Zanhua Rong,Bo Zhao,Yajun Wang,Xuemei Tang","doi":"10.1002/art.43417","DOIUrl":"https://doi.org/10.1002/art.43417","url":null,"abstract":"OBJECTIVEThe therapeutic effects of Telitacicept combined with standard of care (SoC) in childhood-onset systemic lupus erythematosus (cSLE) remain unclear. This study aims to evaluate its efficacy in comparison with Belimumab combined with SoC.METHODSWe performed a prospective cohort study across 7 tertiary hospitals in China, enrolling patients aged 5-18 with cSLE. Primary endpoints included the proportions of patients attaining Lupus Low Disease Activity State (LLDAS) and Doris at 3, 6, and 12 months after treatment, complemented by relapse rates and steroid tapering metrics. Propensity score-based inverse probability of treatment weighting (IPTW) was employed to address baseline imbalances between the Telitacicept (n=60) and the historical control group treated with Belimumab (n=67).RESULTSAmong 60 enrolled patients (median follow-up 12 [IQR 6-12] months), LLDAS/Doris achievement rates progressively increased from 19.6%/7.8% at 6months to 65.7%/37.1% at 12 months. Flare rates remained low (3-month: 1.7%; 6-month:11.8%; 12-month: 14.3%). Notably, 74.3% of patients achieved prednisone doses ≤7.5 mg/day by 12 months (vs. baseline 13.3%, P<0.0001). IPTW-adjusted analyses demonstrated comparable efficacy between the Telitacicept and Belimumab groups across all endpoints in terms of LLDAS/Doris attainment, steroid reduction, and immunological normalization (all P > 0.05).CONCLUSIONTelitacicept combined with SoC exhibited significant improvements in disease activity, steroid reduction, and immunological markers, with therapeutic outcomes comparable to Belimumab in cSLE management.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"101 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373770","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}
Jian Yue,Courtney E LeSon,Casey A Rimland,Kailey Brodeur,Rachel Weng,Evan E Hsu,Michael T Lam,Manpreet Meyer,Seigo Okada,Andrew L D Hsu,Musaab A Alhezam,Megan M Perron,Olha Halyabar,Fatma Dedeoglu,Peter A Nigrovic,Akiko Shimamura,R Grant Rowe,Megan A Cooper,Tiphanie P Vogel,Miriah Gillispie-Taylor,Rosemary Peterson,Clara Lin,Katherine D Nowicki,Kaylee Dollerschell,Taizo A Nakano,Roxane Labrosse,Alexis-Virgil Cochino,Andreea Ioan,Leonardo Oliveira Mendonca,Samar Freschi Barros,Jorge Kalil,Javier Perez Rojas,Alicia Diaz Kuan,Eric S Sobel,Taha Moussa,Samuel Shang Ming Lee,Li Wearn Koh,Archana Khan,Sodality Sutnga,Raju Khubchandani,Walaa Shoman,Yasmine El Chazli,Benzeeta Pinto,Chengappa Kavadichanda,Roshini S Abraham,Xiangwei Sun,Qing Zhou,Gsrsnk Naidu,Aman Sharma,Carl Esperanzate,Daniel L Kastner,Ivona Aksentijevich,Susan J Kelly,Michael Hershfield,Teresa K Tarrant,Pui Y Lee
OBJECTIVESDeficiency of adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disease manifested as polyarteritis nodosa, stroke, and bone marrow failure. Leveraging an international cohort of 200 DADA2 cases, we aimed to characterize the diagnostic utility of a plasma ADA2 enzyme activity assay and understand the implications of residual ADA2 activity.METHODSData were collected from individuals who underwent ADA2 testing from 2018 to 2025. Plasma ADA2 activity was determined using an established spectrophotometric assay. ADA2 variants were analyzed in transfected cells by enzyme assay and western blotting.RESULTSWe determined that plasma ADA2 activity is 99.0%/96.0% sensitive, and 99.7%/98.8% specific in distinguishing genetically confirmed DADA2 cases from controls and carriers, respectively. Eighteen individuals with DADA2 (9%) possessed detectable ADA2 activity, including several cases with levels seen in carriers. Residual ADA2 activity was associated with the vasculitis / inflammatory phenotype but not with disease severity. Genotype analysis revealed that 14/18 cases with residual plasma activity possessed at least one hypomorphic missense variant with >20% residual ADA2 function when overexpressed in 293T cells, often occurring in trans with a more deleterious variant. In vitro analysis revealed that missense ADA2 variants exert variable dominant-negative effects by forming large intracellular protein aggregates via disulfide bond formation at a cysteine residue (Cys408).CONCLUSIONWe confirmed the utility of plasma ADA2 activity as a diagnostic assay and showed that the inflammatory phenotype of DADA2 occurred in cases with residual activity. In vitro findings illustrate potential interactions of ADA2 variants to synergistically disrupt protein function.
{"title":"Diagnostic implications and correlates of plasma ADA2 activity and ADA2 variants.","authors":"Jian Yue,Courtney E LeSon,Casey A Rimland,Kailey Brodeur,Rachel Weng,Evan E Hsu,Michael T Lam,Manpreet Meyer,Seigo Okada,Andrew L D Hsu,Musaab A Alhezam,Megan M Perron,Olha Halyabar,Fatma Dedeoglu,Peter A Nigrovic,Akiko Shimamura,R Grant Rowe,Megan A Cooper,Tiphanie P Vogel,Miriah Gillispie-Taylor,Rosemary Peterson,Clara Lin,Katherine D Nowicki,Kaylee Dollerschell,Taizo A Nakano,Roxane Labrosse,Alexis-Virgil Cochino,Andreea Ioan,Leonardo Oliveira Mendonca,Samar Freschi Barros,Jorge Kalil,Javier Perez Rojas,Alicia Diaz Kuan,Eric S Sobel,Taha Moussa,Samuel Shang Ming Lee,Li Wearn Koh,Archana Khan,Sodality Sutnga,Raju Khubchandani,Walaa Shoman,Yasmine El Chazli,Benzeeta Pinto,Chengappa Kavadichanda,Roshini S Abraham,Xiangwei Sun,Qing Zhou,Gsrsnk Naidu,Aman Sharma,Carl Esperanzate,Daniel L Kastner,Ivona Aksentijevich,Susan J Kelly,Michael Hershfield,Teresa K Tarrant,Pui Y Lee","doi":"10.1002/art.43412","DOIUrl":"https://doi.org/10.1002/art.43412","url":null,"abstract":"OBJECTIVESDeficiency of adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disease manifested as polyarteritis nodosa, stroke, and bone marrow failure. Leveraging an international cohort of 200 DADA2 cases, we aimed to characterize the diagnostic utility of a plasma ADA2 enzyme activity assay and understand the implications of residual ADA2 activity.METHODSData were collected from individuals who underwent ADA2 testing from 2018 to 2025. Plasma ADA2 activity was determined using an established spectrophotometric assay. ADA2 variants were analyzed in transfected cells by enzyme assay and western blotting.RESULTSWe determined that plasma ADA2 activity is 99.0%/96.0% sensitive, and 99.7%/98.8% specific in distinguishing genetically confirmed DADA2 cases from controls and carriers, respectively. Eighteen individuals with DADA2 (9%) possessed detectable ADA2 activity, including several cases with levels seen in carriers. Residual ADA2 activity was associated with the vasculitis / inflammatory phenotype but not with disease severity. Genotype analysis revealed that 14/18 cases with residual plasma activity possessed at least one hypomorphic missense variant with >20% residual ADA2 function when overexpressed in 293T cells, often occurring in trans with a more deleterious variant. In vitro analysis revealed that missense ADA2 variants exert variable dominant-negative effects by forming large intracellular protein aggregates via disulfide bond formation at a cysteine residue (Cys408).CONCLUSIONWe confirmed the utility of plasma ADA2 activity as a diagnostic assay and showed that the inflammatory phenotype of DADA2 occurred in cases with residual activity. In vitro findings illustrate potential interactions of ADA2 variants to synergistically disrupt protein function.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"144 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373769","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}
Victoria K Shanmugam,Carmen Ufret-Vincenty,Xinrui Li,Janine A Clayton
{"title":"The Inaugural NIH-Wide Strategic Plan for Autoimmune Disease Research (FY2026-2030).","authors":"Victoria K Shanmugam,Carmen Ufret-Vincenty,Xinrui Li,Janine A Clayton","doi":"10.1002/art.43411","DOIUrl":"https://doi.org/10.1002/art.43411","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"66 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319253","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}
{"title":"Interleukin (IL)‐5, Eosinophils and IL‐5 Pathway Inhibitors in Eosinophilic Granulomatosis with Polyangiitis.","authors":"Alvise Berti, Christian Pagnoux","doi":"10.1002/art.43409","DOIUrl":"https://doi.org/10.1002/art.43409","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"54 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295810","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}
Ji Soo Kim,Rachel S Wallwork,Carrie Richardson,Adrianne Woods,Monica Mukherjee,Steven Hsu,Julie J Paik,Christopher A Mecoli,Laura K Hummers,Fredrick M Wigley,Scott L Zeger,Ami A Shah
BACKGROUNDCardiac involvement in systemic sclerosis (SSc) is a leading cause of death. We sought to investigate predictors of incident left ventricular systolic dysfunction (LVSD) and cardiac recovery in SSc.METHODS2,303 patients in the Johns Hopkins Scleroderma Center Research Registry and 13,209 echocardiograms were analyzed. We identified predictors associated with incident LVSD defined by transitions in left ventricular (LV) ejection fraction (EF) states (EF≥50% declining to <50% and EF>35% dropping to ≤35% [severe LVSD]) by fitting multivariate logistic regression models with time-varying and invariant variables. Variables associated with cardiac recovery were identified by fitting multivariate logistic regression models using important variables identified from random forest analysis.RESULTSMale sex, Black race, diffuse skin disease, higher mRSS, echocardiographic evidence of pulmonary hypertension (PH), kidney disease, and atrial fibrillation (AFib) were associated with increased odds of incident LVSD (EF<50%), while anti-centromere and anti-topoisomerase-1 were protective. Male sex, higher mRSS, PH, skeletal myopathy, kidney disease, AFib, and anti-Ku antibodies were associated with higher odds of incident severe LVSD (EF≤35%). For previous EF<50%, tendon friction rubs were associated with lower odds of cardiac recovery, and anti-RNA polymerase III (POLR3) with higher odds. For previous EF≤35%, diabetes was associated with lower odds of recovering to EF>35%.CONCLUSIONSDistinct demographic, SSc-specific and cardiac characteristics associate with increased risk of incident LVSD in SSc, with skeletal myopathy and anti-Ku antibodies being important risk factors for severe disease. Some patients improve, which is more likely in anti-POLR3-positive patients.
{"title":"Identification of risk factors for incident left ventricular systolic dysfunction and predictors of cardiac recovery in patients with systemic sclerosis.","authors":"Ji Soo Kim,Rachel S Wallwork,Carrie Richardson,Adrianne Woods,Monica Mukherjee,Steven Hsu,Julie J Paik,Christopher A Mecoli,Laura K Hummers,Fredrick M Wigley,Scott L Zeger,Ami A Shah","doi":"10.1002/art.43408","DOIUrl":"https://doi.org/10.1002/art.43408","url":null,"abstract":"BACKGROUNDCardiac involvement in systemic sclerosis (SSc) is a leading cause of death. We sought to investigate predictors of incident left ventricular systolic dysfunction (LVSD) and cardiac recovery in SSc.METHODS2,303 patients in the Johns Hopkins Scleroderma Center Research Registry and 13,209 echocardiograms were analyzed. We identified predictors associated with incident LVSD defined by transitions in left ventricular (LV) ejection fraction (EF) states (EF≥50% declining to <50% and EF>35% dropping to ≤35% [severe LVSD]) by fitting multivariate logistic regression models with time-varying and invariant variables. Variables associated with cardiac recovery were identified by fitting multivariate logistic regression models using important variables identified from random forest analysis.RESULTSMale sex, Black race, diffuse skin disease, higher mRSS, echocardiographic evidence of pulmonary hypertension (PH), kidney disease, and atrial fibrillation (AFib) were associated with increased odds of incident LVSD (EF<50%), while anti-centromere and anti-topoisomerase-1 were protective. Male sex, higher mRSS, PH, skeletal myopathy, kidney disease, AFib, and anti-Ku antibodies were associated with higher odds of incident severe LVSD (EF≤35%). For previous EF<50%, tendon friction rubs were associated with lower odds of cardiac recovery, and anti-RNA polymerase III (POLR3) with higher odds. For previous EF≤35%, diabetes was associated with lower odds of recovering to EF>35%.CONCLUSIONSDistinct demographic, SSc-specific and cardiac characteristics associate with increased risk of incident LVSD in SSc, with skeletal myopathy and anti-Ku antibodies being important risk factors for severe disease. Some patients improve, which is more likely in anti-POLR3-positive patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283983","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}
Disease-specific mortality statistics are useful measures of disease burden. Population-based studies from a few United States counties have reported mortality in systemic autoimmune diseases (SAID). However, due to substantial differences in the population structure of these counties as well as relatively small numbers of SAID deaths in these counties, it is difficult to extrapolate their findings to assess the SAIDs' national burden. In this regard, national mortality databases offer a large reference population, which is hard to assemble in individual SAIDs. However, two concerns are persistently raised regarding mortality databases for SAIDs: misclassification and under-recording. While misclassification of SAIDs is common in health records and administrative databases, it appears to be rare on death certificates among decedents that did not have a SAID. However, SAIDs are under-recorded in death certificates. The under-recording of SAIDs does not differ by sex and race/ethnicity, but it is common in elderly that die of cardiovascular diseases, neoplasms, and chronic obstructive pulmonary disease. SAIDs' under-recording may occur, because it may be difficult to assign a specific SAID manifestation or treatment complication responsible for death. Furthermore, a SAID is commonly listed as a contributing cause, rather than as the underlying cause of death, on death certificates, which advocates using the multiple-causes-of-death database for SAIDs. Nevertheless, until we have large-scale prospective outcomes data, mortality data from the National Vital Statistics System offer the valuable estimates of SAIDs' national burden, which can be used for setting research priorities, healthcare policy planning, resource allocation, and precision public health.
{"title":"National Mortality Databases to Assess Disease Burden in Systemic Autoimmune Diseases: A Valuable Resource, But with Limitations.","authors":"Ram Raj Singh","doi":"10.1002/art.43410","DOIUrl":"https://doi.org/10.1002/art.43410","url":null,"abstract":"Disease-specific mortality statistics are useful measures of disease burden. Population-based studies from a few United States counties have reported mortality in systemic autoimmune diseases (SAID). However, due to substantial differences in the population structure of these counties as well as relatively small numbers of SAID deaths in these counties, it is difficult to extrapolate their findings to assess the SAIDs' national burden. In this regard, national mortality databases offer a large reference population, which is hard to assemble in individual SAIDs. However, two concerns are persistently raised regarding mortality databases for SAIDs: misclassification and under-recording. While misclassification of SAIDs is common in health records and administrative databases, it appears to be rare on death certificates among decedents that did not have a SAID. However, SAIDs are under-recorded in death certificates. The under-recording of SAIDs does not differ by sex and race/ethnicity, but it is common in elderly that die of cardiovascular diseases, neoplasms, and chronic obstructive pulmonary disease. SAIDs' under-recording may occur, because it may be difficult to assign a specific SAID manifestation or treatment complication responsible for death. Furthermore, a SAID is commonly listed as a contributing cause, rather than as the underlying cause of death, on death certificates, which advocates using the multiple-causes-of-death database for SAIDs. Nevertheless, until we have large-scale prospective outcomes data, mortality data from the National Vital Statistics System offer the valuable estimates of SAIDs' national burden, which can be used for setting research priorities, healthcare policy planning, resource allocation, and precision public health.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"125 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283529","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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