{"title":"Reply to the letter regarding \"Granulomatosis with Polyangiitis Presenting as Strawberry Gingivitis: Diagnostic Challenges with Negative ANCA\".","authors":"Hanghang Liu, Xian Liu","doi":"10.1002/art.43172","DOIUrl":"https://doi.org/10.1002/art.43172","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778667","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":"The ever-expanding connections between PAD4 and rheumatoid arthritis.","authors":"Miriam A Shelef, V Michael Holers","doi":"10.1002/art.43170","DOIUrl":"https://doi.org/10.1002/art.43170","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778671","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":"New insights into the multistage development of rheumatoid arthritis","authors":"Lars Klareskog","doi":"10.1002/art.43171","DOIUrl":"https://doi.org/10.1002/art.43171","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"73 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775332","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}
Jason Liebowitz, Hila Milo Rasouly, Kelsie Bogyo, Lynn Petukhova, Elana J Bernstein, Daniella M Schwartz, Peter C Grayson, David Beck, Yiming Luo
{"title":"The Present and Future of Genetic Sequencing as Applied to Diagnosis and Management in Rheumatology.","authors":"Jason Liebowitz, Hila Milo Rasouly, Kelsie Bogyo, Lynn Petukhova, Elana J Bernstein, Daniella M Schwartz, Peter C Grayson, David Beck, Yiming Luo","doi":"10.1002/art.43169","DOIUrl":"https://doi.org/10.1002/art.43169","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778713","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}
Ju Yeon Kim, Se Rim Choi, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Jun Won Park
ObjectiveAlthough previous studies show that primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is effective in patients with rheumatic diseases receiving immunosuppressive treatment, there is limited evidence regarding the optimal timing for prophylaxis withdrawal. This study aimed to identify the risk factors for PJP despite prophylaxis and provide evidence for an optimal prophylaxis schedule.MethodsThis case‐control study included 1,294 prophylactic episodes in 1,148 patients with rheumatic disease who received immunosuppressants and prophylactic trimethoprim‐sulfamethoxazole (TMP‐SMX). The primary outcome was a one‐year incidence of PJP. A Cox proportional hazards model with LASSO was used to evaluate clinical factors associated with outcomes.ResultsDuring 1,174 person‐years of observation, 10 cases of PJP were identified, with an incidence rate of 0.85 per 100 person‐years. The mean (standard deviation [SD]) duration of TMP‐SMX prophylaxis was 181.9 (128.7) days. Except in one case, PJP occurred after discontinuation of TMP‐SMX, with a median (interquartile range [IQR]) interval of 117.0 (86.0‐161.0) days. The dose of glucocorticoids at the time of TMP‐SMX discontinuation was significantly higher in the PJP group relative to the control group (median [IQR]: 22 [20‐40] vs 10 [5‐15] mg). Discontinuing TMP‐SMX while on a glucocorticoid dose >12.5 mg/day of prednisone equivalent significantly increased the risk of PJP (adjusted hazard ratio: 13.84 [95% confidence interval, 1.71‐111.80]). There were 63 cases of adverse events during the observation period, and seven (11.1%) were attributed to TMP‐SMX with probable causality.ConclusionTapering glucocorticoids with 12.5 mg/day of prednisone equivalent could be a reasonable timepoint to initiate the withdrawal of PJP prophylaxis in patients with rheumatic diseases.image
{"title":"Clinical factors associated with pneumocystis pneumonia despite its primary prophylaxis: When to stop prophylaxis?","authors":"Ju Yeon Kim, Se Rim Choi, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Jun Won Park","doi":"10.1002/art.43167","DOIUrl":"https://doi.org/10.1002/art.43167","url":null,"abstract":"ObjectiveAlthough previous studies show that primary prophylaxis against <jats:italic>Pneumocystis jirovecii</jats:italic> pneumonia (PJP) is effective in patients with rheumatic diseases receiving immunosuppressive treatment, there is limited evidence regarding the optimal timing for prophylaxis withdrawal. This study aimed to identify the risk factors for PJP despite prophylaxis and provide evidence for an optimal prophylaxis schedule.MethodsThis case‐control study included 1,294 prophylactic episodes in 1,148 patients with rheumatic disease who received immunosuppressants and prophylactic trimethoprim‐sulfamethoxazole (TMP‐SMX). The primary outcome was a one‐year incidence of PJP. A Cox proportional hazards model with LASSO was used to evaluate clinical factors associated with outcomes.ResultsDuring 1,174 person‐years of observation, 10 cases of PJP were identified, with an incidence rate of 0.85 per 100 person‐years. The mean (standard deviation [SD]) duration of TMP‐SMX prophylaxis was 181.9 (128.7) days. Except in one case, PJP occurred after discontinuation of TMP‐SMX, with a median (interquartile range [IQR]) interval of 117.0 (86.0‐161.0) days. The dose of glucocorticoids at the time of TMP‐SMX discontinuation was significantly higher in the PJP group relative to the control group (median [IQR]: 22 [20‐40] vs 10 [5‐15] mg). Discontinuing TMP‐SMX while on a glucocorticoid dose >12.5 mg/day of prednisone equivalent significantly increased the risk of PJP (adjusted hazard ratio: 13.84 [95% confidence interval, 1.71‐111.80]). There were 63 cases of adverse events during the observation period, and seven (11.1%) were attributed to TMP‐SMX with probable causality.ConclusionTapering glucocorticoids with 12.5 mg/day of prednisone equivalent could be a reasonable timepoint to initiate the withdrawal of PJP prophylaxis in patients with rheumatic diseases.<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/art43167-toc-0001-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"34 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766389","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}
Taejoon Won, Pooja Naik, Megan K. Wood, Hong Wang, Monica V. Talor, Jing Shi, William Bracamonte‐Baran, Mekha A. Thomas, Camille M. Jaime, Wonyoung Jo, Shreyanshu Ray, Catherine A. Foss, Felipe Andrade, Daniela Čiháková, Erika Darrah
ObjectiveAutoantibodies targeting peptidylarginine deiminase 4 (PAD4), an enzyme involved in protein citrullination, are found in a subset of rheumatoid arthritis (RA) patients with severe joint disease. However, the mechanisms by which anti‐PAD4 antibodies participate in disease pathogenesis are incompletely defined.MethodsWe investigated the role of anti‐PAD4 monoclonal antibodies derived from RA patients using a collagen‐induced arthritis (CIA) mouse model and human monocyte in vitro cultures. The cellular targets of anti‐PAD4 antibodies were identified using mouse knee joint cells and human peripheral blood mononuclear cells (PBMC). In addition, PAD4 gene and protein expression were assessed using human fibroblast‐like synoviocyte in vitro cultures and a single‐cell RNA sequencing dataset obtained from RA patients.ResultsWe show that anti‐PAD4 antibody treatment augmented disease severity in the CIA mouse model, with increased joint damage, myeloid cell infiltration, and synovial fibroblast activation. Arthritic mice administered with anti‐PAD4 antibodies had an increased proportion of IL‐17A, TNF‐α, and IFN‐γ‐producing T cells. Anti‐PAD4 antibodies preferentially bound monocytes in both humans and mice, eliciting pro‐inflammatory chemokine production by human monocytes in vitro. T cell cytokines enhanced by anti‐PAD4 antibodies in the CIA model, i.e. IL‐17A, TNF‐α, and IFN‐γ, synergized to induce a pro‐inflammatory phenotype in human fibroblast‐like synoviocytes.ConclusionOur findings suggest a model in which anti‐PAD4 antibody binding to monocytes triggers an inflammatory cascade that promotes immune cell recruitment to the joint and T cell activation, culminating in synovial fibroblast activation and the development of more severe arthritis.image
{"title":"Anti‐Peptidylarginine‐4 Autoantibodies Derived from Patients with Rheumatoid Arthritis Exert Pathogenic Effects by Activating Monocytes and Exacerbating Inflammatory Arthritis","authors":"Taejoon Won, Pooja Naik, Megan K. Wood, Hong Wang, Monica V. Talor, Jing Shi, William Bracamonte‐Baran, Mekha A. Thomas, Camille M. Jaime, Wonyoung Jo, Shreyanshu Ray, Catherine A. Foss, Felipe Andrade, Daniela Čiháková, Erika Darrah","doi":"10.1002/art.43168","DOIUrl":"https://doi.org/10.1002/art.43168","url":null,"abstract":"ObjectiveAutoantibodies targeting peptidylarginine deiminase 4 (PAD4), an enzyme involved in protein citrullination, are found in a subset of rheumatoid arthritis (RA) patients with severe joint disease. However, the mechanisms by which anti‐PAD4 antibodies participate in disease pathogenesis are incompletely defined.MethodsWe investigated the role of anti‐PAD4 monoclonal antibodies derived from RA patients using a collagen‐induced arthritis (CIA) mouse model and human monocyte <jats:italic>in vitro</jats:italic> cultures. The cellular targets of anti‐PAD4 antibodies were identified using mouse knee joint cells and human peripheral blood mononuclear cells (PBMC). In addition, PAD4 gene and protein expression were assessed using human fibroblast‐like synoviocyte <jats:italic>in vitro</jats:italic> cultures and a single‐cell RNA sequencing dataset obtained from RA patients.ResultsWe show that anti‐PAD4 antibody treatment augmented disease severity in the CIA mouse model, with increased joint damage, myeloid cell infiltration, and synovial fibroblast activation. Arthritic mice administered with anti‐PAD4 antibodies had an increased proportion of IL‐17A, TNF‐α, and IFN‐γ‐producing T cells<jats:italic>.</jats:italic> Anti‐PAD4 antibodies preferentially bound monocytes in both humans and mice, eliciting pro‐inflammatory chemokine production by human monocytes <jats:italic>in vitro</jats:italic>. T cell cytokines enhanced by anti‐PAD4 antibodies in the CIA model, i.e. IL‐17A, TNF‐α, and IFN‐γ, synergized to induce a pro‐inflammatory phenotype in human fibroblast‐like synoviocytes.ConclusionOur findings suggest a model in which anti‐PAD4 antibody binding to monocytes triggers an inflammatory cascade that promotes immune cell recruitment to the joint and T cell activation, culminating in synovial fibroblast activation and the development of more severe arthritis.<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/art43168-toc-0001-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"99 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766391","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}
Huanhuan Liu, Anupama Binoy, Siqi Ren, Thomas C. Martino, Anna E. Miller, Craig R. G. Willis, Shivakumar R. Veerabhadraiah, Joanna Bons, Jacob P. Rose, Birgit Schilling, Michael J. Jurynec, Shouan Zhu
ObjectivesChondrocyte metabolic dysfunction plays an important role in osteoarthritis (OA) development during aging and obesity. Protein post‐translational modifications (PTMs) have recently emerged as an important regulator of cellular metabolism. We aim to study one type of PTM, lysine malonylation (MaK) and its regulator Sirt5 in OA development.MethodsHuman and mouse cartilage tissues were used to measure SIRT5 and MaK levels. Both systemic and cartilage‐specific conditional knockout mouse models were subject to high‐fat diet (HFD) treatment to induce obesity and OA. Proteomics analysis was performed in Sirt5‐/‐ and WT chondrocytes. SIRT5 mutation was identified in the Utah Population Database (UPDB).ResultsWe found that SIRT5 decreases while MAK increases in the cartilage during aging. A combination of Sirt5 deficiency and obesity exacerbates joint degeneration in a sex dependent manner in mice. We further delineate the malonylome in chondrocytes, pinpointing MaK's predominant impact on various metabolic pathways such as carbon metabolism and glycolysis. Lastly, we identified a rare coding mutation in SIRT5 that dominantly segregates in a family with OA. The mutation results in substitution of an evolutionally invariant phenylalanine (Phe–F) to leucine (Leu–L) (F101L) in the catalytic domain. The mutant protein results in higher MaK level and decreased expression of cartilage ECM genes and upregulation of inflammation associated genes.ConclusionsWe found that Sirt5 mediated MaK is an important regulator of chondrocyte cellular metabolism and dysregulation of Sirt5‐MaK could be an important mechanism underlying aging and obesity associated OA development.image
{"title":"Sirt5 regulates chondrocyte metabolism and osteoarthritis development through protein lysine malonylation","authors":"Huanhuan Liu, Anupama Binoy, Siqi Ren, Thomas C. Martino, Anna E. Miller, Craig R. G. Willis, Shivakumar R. Veerabhadraiah, Joanna Bons, Jacob P. Rose, Birgit Schilling, Michael J. Jurynec, Shouan Zhu","doi":"10.1002/art.43164","DOIUrl":"https://doi.org/10.1002/art.43164","url":null,"abstract":"ObjectivesChondrocyte metabolic dysfunction plays an important role in osteoarthritis (OA) development during aging and obesity. Protein post‐translational modifications (PTMs) have recently emerged as an important regulator of cellular metabolism. We aim to study one type of PTM, lysine malonylation (MaK) and its regulator Sirt5 in OA development.MethodsHuman and mouse cartilage tissues were used to measure SIRT5 and MaK levels. Both systemic and cartilage‐specific conditional knockout mouse models were subject to high‐fat diet (HFD) treatment to induce obesity and OA. Proteomics analysis was performed in <jats:italic>Sirt5</jats:italic><jats:sup><jats:italic>‐/‐</jats:italic></jats:sup> and WT chondrocytes. SIRT5 mutation was identified in the Utah Population Database (UPDB).ResultsWe found that SIRT5 decreases while MAK increases in the cartilage during aging. A combination of Sirt5 deficiency and obesity exacerbates joint degeneration in a sex dependent manner in mice. We further delineate the malonylome in chondrocytes, pinpointing MaK's predominant impact on various metabolic pathways such as carbon metabolism and glycolysis. Lastly, we identified a rare coding mutation in <jats:italic>SIRT5</jats:italic> that dominantly segregates in a family with OA. The mutation results in substitution of an evolutionally invariant phenylalanine (Phe–F) to leucine (Leu–L) (F101L) in the catalytic domain. The mutant protein results in higher MaK level and decreased expression of cartilage ECM genes and upregulation of inflammation associated genes.ConclusionsWe found that Sirt5 mediated MaK is an important regulator of chondrocyte cellular metabolism and dysregulation of Sirt5‐MaK could be an important mechanism underlying aging and obesity associated OA development.<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/art43164-toc-0001-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"28 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766392","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}
Achille Marino, Maria Vittoria Cicinelli, Elisabetta Miserocchi, Stefania Costi, Francesco Baldo, Maurizio Virgilio Gattinara, Pierluigi Scandale, Scott D Smith, Debra A Goldstein, Dina Baddar, Terese KA Gerges, Timothy M Janetos, Matilde Ruiz-Cruz, Kazuichi Maruyama, Massimiliano Serafino, Paola Camicione, Vishali Gupta, Radgonde Amer, Emilio M Dodds, Sebastian Inchauspe, Marion R Munk, Ester Carreño, Soon-Phaik Chee, Aniruddha Agarwal, Ariel Schlaen, Ramiro A Gómez, Cristobal A. Couto, Moncef Khairallah, Piergiorgio Neri, Cecilia B Chighizola, Roberto F Caporali, Francesco Pichi
This study aims to assess the risk of non-infectious uveitis (NIU) relapse in pediatric patients undergoing Adalimumab (ADA) tapering, evaluating potential predictors of such risk
{"title":"Recurrence Risk in Pediatric Non-Infectious Uveitis during Adalimumab Tapering: An International Multicenter Retrospective Study","authors":"Achille Marino, Maria Vittoria Cicinelli, Elisabetta Miserocchi, Stefania Costi, Francesco Baldo, Maurizio Virgilio Gattinara, Pierluigi Scandale, Scott D Smith, Debra A Goldstein, Dina Baddar, Terese KA Gerges, Timothy M Janetos, Matilde Ruiz-Cruz, Kazuichi Maruyama, Massimiliano Serafino, Paola Camicione, Vishali Gupta, Radgonde Amer, Emilio M Dodds, Sebastian Inchauspe, Marion R Munk, Ester Carreño, Soon-Phaik Chee, Aniruddha Agarwal, Ariel Schlaen, Ramiro A Gómez, Cristobal A. Couto, Moncef Khairallah, Piergiorgio Neri, Cecilia B Chighizola, Roberto F Caporali, Francesco Pichi","doi":"10.1002/art.43165","DOIUrl":"https://doi.org/10.1002/art.43165","url":null,"abstract":"This study aims to assess the risk of non-infectious uveitis (NIU) relapse in pediatric patients undergoing Adalimumab (ADA) tapering, evaluating potential predictors of such risk","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"9 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758608","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":"Short‐Term Risk of Cardiovascular Events in People Newly Diagnosed With Gout: Comment on the article by Cipolletta E et al","authors":"Teng‐Fei Li, Rui‐Jun Bai","doi":"10.1002/art.43163","DOIUrl":"https://doi.org/10.1002/art.43163","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"5 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744782","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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