Arthritis & Rheumatology最新文献

{"title":"Per- and Polyfluoroalkyl Substances and Knee Osteoarthritis: Data From the Osteoarthritis Initiative","authors":"Jeffrey B. Driban PhD,&nbsp;Lisa B. Rokoff PhD,&nbsp;Bing Lu MD, DrPH,&nbsp;Timothy E. McAlindon MD, MPH,&nbsp;Charles B. Eaton MD, MS,&nbsp;Mary B. Roberts MS,&nbsp;Diana Mathes BS,&nbsp;Colleen Lestician BS,&nbsp;Zhijin Carrie Xu PhD,&nbsp;Zhihua Tina Fan PhD,&nbsp;Shawn P. O'Leary BS,&nbsp;Ida K. Haugen MD, PhD,&nbsp;Jérémie Sellam MD, PhD,&nbsp;Alice Courties MD, PhD,&nbsp;Abby F. Fleisch MD, MPH","doi":"10.1002/art.70154","DOIUrl":"10.1002/art.70154","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To examine whether concentrations of specific per- and polyfluoroalkyl substances (PFAS) and a mixture of PFAS relate to incident knee osteoarthritis (KOA) and knee pain progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Among a case-cohort sample from the OA Initiative (n = 1,878), we examined associations of serum concentrations of eight PFAS with odds of developing over the subsequent 48 months (1) symptomatic KOA and (2) a clinically meaningful change in the Western Ontario and McMaster Universities OA Index knee pain score. We used weighted logistic regression to assess single PFAS (continuous and quartiles) and quantile g-computation to assess the PFAS mixture in relation to our outcomes, accounting for sociodemographics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-eight percent of participants were female with a mean age of 62 years and body mass index of 28.6 kg/m². Participants with higher perfluorooctanoic acid (continuous) had greater odds of incident symptomatic KOA (odds ratio [OR] per interquartile range [IQR] 1.12, 95% confidence interval [CI] 1.04–1.21). Participants in the highest quartiles of perfluorononanoic acid (PFNA) had greater odds of incident symptomatic KOA [OR for the third quartile 1.63, 95% CI 1.29–2.07; fourth quartile 1.55, 95% CI 1.19–2.01). Perfluorooctanoic acid may have a nonlinear relationship with the greatest chance of incident symptomatic KOA with serum concentrations between 5.19 and 6.88 ng/mL (OR 1.55, 95% CI 1.21–1.97). Participants with greater perfluorooctanoic acid and PFNA (continuous) had greater odds of knee pain progression (OR per IQR: perfluorooctanoic acid 1.10, 95% CI 1.03–1.18; PFNA 1.06, 95% CI 1.01–1.11). Mixture models showed perfluorooctanoic acid and PFNA were among the PFAS with the strongest positive weights for both outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In a large cohort at risk for KOA, higher perfluorooctanoic acid and PFNA serum concentrations may be associated with a greater likelihood of symptomatic KOA incidence and knee pain progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2082-2088"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Connections","authors":"","doi":"10.1002/art.70318","DOIUrl":"https://doi.org/10.1002/art.70318","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Connections","authors":"","doi":"10.1002/art.70318","DOIUrl":"https://doi.org/10.1002/art.70318","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Do Not Arrest Bone Loss in Patients With Rheumatoid Arthritis: A Long-Term Multicenter Observational Study","authors":"Takafumi Aritomi MD,&nbsp;Koshiro Sonomoto MD, PhD,&nbsp;Shingo Nakayamada MD, PhD,&nbsp;Hiroaki Tanaka MD, PhD,&nbsp;Atsushi Nagayasu MD,&nbsp;Satoshi Kubo MD, PhD,&nbsp;Ippei Miyagawa MD, PhD,&nbsp;Ayako Yamaguchi MD, PhD,&nbsp;Naoaki Ohkubo MD, PhD,&nbsp;Yasuyuki Todoroki MD, PhD,&nbsp;Yurie Satoh-Kanda MD, PhD,&nbsp;Masanobu Ueno MD, PhD,&nbsp;Ryuichiro Kanda MD,&nbsp;Yuya Fujita MD,&nbsp;Masashi Funada MD,&nbsp;Hidenori Sakai MD,&nbsp;Satsuki Matsunaga MD,&nbsp;Hiroaki Tanaka MD,&nbsp;Masayuki Shinojima MD,&nbsp;Hiroki Kawamura MD,&nbsp;Kazuki Takahashi MD,&nbsp;Miyabi Ando MD,&nbsp;Kazuki Haru MD,&nbsp;Yusuke Miyazaki MD, PhD,&nbsp;Kentaro Hanami MD, PhD,&nbsp;Masao Nawata MD, PhD,&nbsp;Shunsuke Fukuyo MD, PhD,&nbsp;Keisuke Nakatsuka MD, PhD,&nbsp;Mikiko Tokunaga MD, PhD,&nbsp;Kazuyoshi Saito MD, PhD,&nbsp;Yoshiya Tanaka MD, PhD","doi":"10.1002/art.70125","DOIUrl":"10.1002/art.70125","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Osteoporosis causes fractures that further increase the disease burden of rheumatoid arthritis (RA); however, osteoporosis treatment rates remain low. Although several studies have reported that biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) can prevent or improve osteoporosis in RA, our large-scale, real-world study showed that one-year b/tsDMARDs use did not arrest osteoporosis progression. This study aimed to examine longer-term changes in bone mineral density (BMD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>BMD was observed for up to five years in patients receiving b/tsDMARDs for active RA. The primary endpoint was change in BMD (T score), and the secondary endpoint was change in T score–related factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 797 patients (antiosteoporosis–, n = 645; antiosteoporosis+, n = 152) were included, with a median 3.1-year follow-up (2,489 patient-years). Clinical Disease Activity Index (CDAI) improved in both groups (antiosteoporosis– 26.0 to 6.6; antiosteoporosis+ 24.4 to 6.8). T scores decreased significantly in the femoral neck and radius in the antiosteoporosis− group but not in the antiosteoporosis+ group (antiosteoporosis–: mean change –0.11 to –0.33, both <i>P</i> &lt; 0.001; antiosteoporosis+ –0.01 to –0.10, <i>P</i> = 0.830 and 0.071, respectively). Overall, 460 patients (58%) experienced a decrease in T score. A high baseline T score correlated with a subsequent decrease, whereas longer osteoporosis treatment duration correlated with an increase. Unexpectedly, the duration of b/tsDMARD use and mean CDAI during observation were not associated with BMD maintenance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Even when RA activity was controlled with b/tsDMARDs, BMD still decreased. This study emphasizes the importance of considering osteoporosis as an independent aspect of RA, beyond inflammation control.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2036-2049"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Carbamylated Protein Antibodies Stabilize Carbamylated Histone H3 to Promote Synovial Activation and Neutrophil Extracellular Trap-Mediated Bone Loss in Rheumatoid Arthritis","authors":"Shuichiro Nakabo MD, PhD,&nbsp;Norio Hanata MD, PhD,&nbsp;Eduardo Patino-Martinez PhD,&nbsp;Ronald Holewinski PhD,&nbsp;Ana Barrera-Vargas MD,&nbsp;Javier Merayo-Chalico MD,&nbsp;Scott A. Coonrod MD,&nbsp;David A. Fox MD,&nbsp;Mariana J. Kaplan MD,&nbsp;Carmelo Carmona-Rivera PhD","doi":"10.1002/art.70158","DOIUrl":"10.1002/art.70158","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Carbamylation, a nonenzymatic post-translational modification, contributes to rheumatoid arthritis (RA) pathogenesis. Anti-carbamylated protein antibodies (anti-CarP) occur in around 50% of patients with RA and associate with greater joint damage. Neutrophil extracellular traps (NETs) are a major source of carbamylated autoantigens. We sought to study how carbamylation and anti-CarP antibodies promote joint pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>NETs were generated with calcium ionophore and analyzed for carbamylation by immunofluorescence, flow cytometry, and mass spectrometry. Enzymatic pathways were interrogated using pharmacologic inhibitors and peptidyl arginine deiminase (PAD)2/4 deficient mice. Degradation kinetics of carbamylated histone H3 (carH3) were evaluated with neutrophil elastase (NE) and anti-CarP IgG from patients with RA. Toll-like receptor 4 (TLR4) activation was quantified using a HEK293 reporter line. RA fibroblast-like synoviocytes (FLS) were stimulated with carH3 or carH3-IgG immune complexes (ICs) and profiled by RNA-sequencing and enzyme-linked immunosorbent assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Histone carbamylation, especially of H3, occurred during NETosis and was independent of peptidylarginine deiminase-4, myeloperoxidase, NE, or oxidative pathways. CarH3 was rapidly degraded by NE, but anti-CarP antibodies protected it from proteolysis. NETs exposed to anti-CarP IgG triggered stronger TLR4 activation and enhanced osteoclastogenesis. In FLS, carH3 and particularly carH3-ICs induced robust up-regulation of pro-inflammatory genes and cytokine secretion (interleukin [IL-]6, IL-8, MCP-1, GM-CSF). Transcriptomic analysis revealed enrichment of immune activation, chemotaxis, and angiogenesis pathways, most pronounced with carH3-IC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Anti-CarP antibodies stabilize carH3 within NETs, amplifying its pro-inflammatory and osteoclastogenic activity. The resulting carH3-IgG ICs potently activate FLS, linking humoral immunity to tissue inflammation and bone destruction in RA. These findings identify carH3 stabilization as a potential therapeutic target in antibody-mediated joint damage.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"78 10","pages":"2074-2081"},"PeriodicalIF":9.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avacopan in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Real-World Safety After Postmarketing Liver Injury Signals.","authors":"Iftach Sagy, Rona M Smith, Lucy Francis, Rachel B Jones","doi":"10.1002/art.70329","DOIUrl":"10.1002/art.70329","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035668","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":"T Cells in Systemic Lupus Erythematosus: Biology and Clinical Value.","authors":"Rachel Simon, Wenliang Pan, George C Tsokos","doi":"10.1002/art.70355","DOIUrl":"10.1002/art.70355","url":null,"abstract":"<p><p>T cells in patients with systemic lupus erythematosus display multiple defects that contribute to disease pathogenesis and organ damage. Understanding the nature of the abnormalities at the cellular, biochemical, molecular, and metabolic level offers opportunities to understand the origin of specific manifestations and disease complications, develop disease biomarkers, establish personalized medicine, and develop effective therapeutics.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035806","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":"Dual Effects of β-TrCP2 Deletion in Bone Homeostasis: Suppression of Osteoclastogenesis and Enhancement of Osteoblast Activity.","authors":"Woo Jung Kim, Sora Han, Hye In Ka, Sun Young Lee, Jiwon Kim, Hyunjeong Joo, Sujung Soh, Gaeun Oh, Kyung Hyun Yoo, Seung Hyun Han, Yeongkag Kwon, Choogon Lee, Kyung-Hyun Park-Min, Se Hwan Mun, Young Yang","doi":"10.1002/art.70351","DOIUrl":"10.1002/art.70351","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to elucidate the role of beta-transducin repeat-containing protein 2 (β-TrCP2) in bone homeostasis for its potential as a therapeutic target for osteoporosis.</p><p><strong>Methods: </strong>The role of β-TrCP2 in bone phenotypes was investigated using systemic β-TrCP1 knockout (KO) and β-TrCP2KO mice, along with myeloid-specific conditional β-TrCP2KO (β-TrCP2^ΔM) mice. Bone microarchitecture was assessed by micro-computed tomography and osteoclast and osteoblast parameters by histomorphometry. Osteoclast resorptive activity was evaluated using dentine slice pit assays. Mechanisms regulating osteoclastogenesis were investigated by RNA sequencing, real-time quantitative polymerase chain reaction, immunoprecipitation, and immunoblotting. Bone formation and injury-induced repair were assessed by dynamic histomorphometry and drill-hole defect model. Therapeutic potential was evaluated in ovariectomized wild-type (WT) and β-TrCP2KO mice.</p><p><strong>Results: </strong>β-TrCP2KO and β-TrCP2^ΔM mice exhibited the increased bone mass and reduced osteoclast numbers compared to WT, but not β-TrCP1KO, mice. The β-TrCP2KO bone marrow-derived myeloid cells were treated with RANKL. The activity and markers of osteoclast were decreased and of interferon-β (IFNβ) was increased. Mechanistically, β-TrCP2-mediated IKKε ubiquitination and degradation are a critical event for enhancing IFNβ expression via IRF3 by RANKL or lipopolysaccharide stimulation. β-TrCP2KO mice showed increased osteoblast differentiation and bone formation through β-catenin stabilization and up-regulation of osteogenic genes. In post-osteoporosis induction therapeutic ovariectomized model, β-TrCP2KO mice were protected from bone loss through both decreased osteoclast formation and enhanced osteoblast activity.</p><p><strong>Conclusion: </strong>β-TrCP2 regulates osteoclast formation by modulating IKKε-IRF3-IFNβ and NF-κB signaling pathway and influences osteoblast activity by β-catenin accumulation. This study suggests that β-TrCP2 has potential as a novel therapeutic target for osteoporosis.</p>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035736","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":"B-cell Maturation Antigen (BCMA)-CAR-T Therapy in a Patient with Triple Positive Antiphospholipid Syndrome and Recurrent Alveolar Bleeding.","authors":"Dror Mevorach, Shlomo Elias, Shlomit Kfir-Erenfeld, Adi Tabib, Dotan Cohen, Rottem Kuint, Eran Zimran, Elena Karger, Nathalie Asheri, Miri Assayag, Batia Avni, Sigal Grisariu, Cyrille J Cohen, Polina Stepensky, Chamutal Gur","doi":"10.1002/art.70322","DOIUrl":"https://doi.org/10.1002/art.70322","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035691","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":"From ADVOCATE to ADVOGATE: Is This the End of Avacopan?","authors":"Gavin B Chapman, Dan Pugh, Neeraj Dhaun","doi":"10.1002/art.70352","DOIUrl":"10.1002/art.70352","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035809","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}