Arthritis & Rheumatology最新文献

{"title":"Serum cytokine profiling differentiates underlying diseases in cytokine storm syndrome.","authors":"Shuya Kaneko,Maho Hatano,Asami Shimbo,Futaba Miyaoka,Hitoshi Irabu,Yuko Akutsu,Yuko Hayashi,Mao Mizuta,Yasuo Nakagishi,Keiji Akamine,Naomi Iwata,Kenji Furuno,Takayuki Tanaka,Kazuyuki Ueno,Shuhei Fujita,Koji Yokoyama,Toshinori Minato,Kazushi Izawa,Takahiro Yasumi,Tadashi Matsubayashi,Tadashi Hosoya,Hiroki Nishikawa,Junya Fujimura,Ryoko Asano,Yuko Sugita,Kenichi Watanabe,Anna Kobayashi,Takuya Endo,Katsuhide Eguchi,Ryuta Nishikomori,Ryuhei Yasuoka,Takaki Asano,Miyako Kanno,Kazuya Hamada,Yuji Fujita,Daisuke Hayashi,Shojiro Watanabe,Takeshi Shiba,Shinsuke Yasuda,Masaaki Mori,Hirokazu Kanegane,Masatoshi Takagi,Masaki Shimizu","doi":"10.1002/art.43349","DOIUrl":"https://doi.org/10.1002/art.43349","url":null,"abstract":"OBJECTIVECytokine storm syndrome (CSS), commonly associated with hemophagocytic lymphohistiocytosis (HLH), is a fatal hyperinflammatory syndrome. Differentiating the underlying diseases responsible for CSS is essential for timely therapeutic decisions. This study explored the clinical usefulness of serum cytokine profiling in distinguishing underlying diseases in patients with CSS.METHODSSerum samples were collected from 143 adult and pediatric patients with CSS and 22 healthy controls. The cohort included patients with various diagnoses of primary and secondary HLH, and Kawasaki disease (KD)-like hyperinflammatory syndromes. Serum levels of 48 cytokines were analyzed in 97 patients using a bead-based multiplex immunoassay (Luminex assay). Serum levels of IFN-α, IL-18, IL-6, CXCL9, and sTNF-RII were measured in 165 participants using enzyme-linked immunosorbent assay (ELISA).RESULTSLuminex assay categorized patients with CSS into five clusters based on serum cytokine patterns. ELISA revealed distinct cytokine patterns, wherein patients with histiocytic necrotizing lymphadenitis-associated HLH and systemic lupus erythematosus-associated-MAS showed elevated IFN-α; systemic juvenile idiopathic arthritis- and adult-onset Still's disease-associated MAS, XIAP deficiency with HLH, and NLRC4-associated autoinflammatory disorder exhibited higher IL-18 levels. Additionally, KD shock syndrome had higher IL-6 levels than the other groups. CXCL9 was significantly elevated in patients with virus-associated HLH, familial HLH, malignant lymphoma-associated HLH, and KD-MAS. Multisystem inflammatory syndrome in children and toxic shock syndrome also showed moderate elevations of CXCL9 and IL-6 levels.CONCLUSIONSerum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"156 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796796","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":"Epidermal Interferon kappa drives cutaneous lupus-like lesions, photosensitivity and systemic autoimmunity in vivo.","authors":"Benjamin Klein,Deborah J Colesa,Yiqing Gao,Patrick A O'Brien,Lin Zhang,Lori Lowe,Kelsey E McNeely,Nguyen Thi Kim Nguyen,Svenja Henning,Mehrnaz Gharaee-Kermani,Jeffrey B Hodgin,Jacob W S Martens,Johann E Gudjonsson,Celine C Berthier,J Michelle Kahlenberg","doi":"10.1002/art.43350","DOIUrl":"https://doi.org/10.1002/art.43350","url":null,"abstract":"OBJECTIVEKeratinocyte-derived interferon kappa (IFN-κ) is chronically overexpressed in human non-lesional systemic lupus erythematosus (SLE) skin. Recent evidence suggests that epidermal signals instruct the immune system in SLE, but whether epidermal IFN-κ alone is sufficient to drive lupus phenotypes has not been investigated. This study aimed to identify whether epidermal-specific overexpression of Interferon kappa (Ifnk) results in lupus-like cutaneous and systemic inflammation.METHODSWe compared three month (young) and twelve month (aged) old Balb/c mice that overexpress Ifnk in the epidermis under the keratin 14 promoter (transgenic, TG) with age-matched Balb/c wild type mice (WT) and assessed local and systemic immune responses at baseline and after UV exposure. Skin lesions were assessed by histopathology, bulk RNA sequencing and immunohistochemistry and subsequently compared to human cutaneous lupus erythematosus (CLE). Flow cytometry on lymph nodes and splenocytes at baseline and after UV exposure was performed to phenotype immune cell compositions.RESULTSIfnk TG mice spontaneously develop CLE-like lesions and systemic immune dysregulation. Lesions show facial predominance, lymphocytic infiltration, immune complex deposition and a transcriptional signature reflective of human CLE. Ifnk TG mice exhibit increased immune cell activation and spontaneous signs of systemic autoimmunity with higher anti-dsDNA-antibodies, lymphadenopathy and splenomegaly, but lack signs of renal inflammation. UV exposure enhanced cutaneous inflammation and splenic T cell activation in Ifnk TG mice.CONCLUSIONTogether, we describe a new CLE mouse model that recapitulates features of human CLE and substantiates the role of epidermal IFN-κ as a driver of CLE, photosensitivity and systemic inflammation.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"17 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796797","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":"When less is more, none can be even better: Rethinking routine follow-up of chronic disease exemplified with rheumatoid arthritis.","authors":"Alen Brkic,Glenn Haugeberg","doi":"10.1002/art.43346","DOIUrl":"https://doi.org/10.1002/art.43346","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769785","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":"Investigation of Lysosome-Associated Membrane Protein 3 Highlights the Role of Lysosome in Pathophysiology and Treatment of Sjögren's Disease.","authors":"Hiroyuki Nakamura,Tsutomu Tanaka,Masayuki Noguchi,Tatsuya Atsumi,Blake M Warner,John A Chiorini","doi":"10.1002/art.43347","DOIUrl":"https://doi.org/10.1002/art.43347","url":null,"abstract":"Lysosome-associated membrane protein 3 (LAMP3) is a unique lysosomal membrane protein specifically expressed in mature dendritic cells and type II pneumocytes. Its ectopic expression in salivary gland epithelial cells (SGECs) is induced by type I interferon (IFN) signaling and further amplified through Toll-like receptor 7 (TLR7) activation, which is implicated in the pathogenesis of Sjögren's disease (SjD). This aberrant upregulation disrupts glandular function by promoting endolysosomal degradation of aquaporin 5 (AQP5) and Na-K-Cl cotransporter-1, leading to impaired fluid secretion and associated clinical sequelae (e.g., dry mouth). Additionally, LAMP3-mediated lysosomal exocytosis of damage-associated molecular patterns enhances monocytic bone morphogenetic protein 6 (BMP6) production, which in turn suppresses AQP5 transcription. Moreover, LAMP3 drives the extracellular vesicle-mediated release of autoantigens, which further amplifies autoimmunity, and lysosome-dependent cell death in SGECs contributes to tissue damage. These findings establish LAMP3 as a pivotal regulatory hinge in SjD pathogenesis, linking IFN-TLR7 signaling, lysosomal dysfunction, and glandular hypofunction. Its central role makes it a compelling therapeutic target, with strategies including IFN and TLR7 pathway inhibitors to limit its induction, restoration of lysosomal function, BMP6 inhibition to preserve AQP5 expression, and aquaporin gene therapy to improve fluid secretion.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"15 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769781","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":"Response to Chepy et al. and Akbarzadeh et al.","authors":"Wieke M van Oostveen,Eva M Hoekstra,E W Nivine Levarht,Ilana B Kotliar,Thomas P Sakmar,René E M Toes,Jeska K de Vries-Bouwstra,Laura H Heitman,Cynthia M Fehres","doi":"10.1002/art.43348","DOIUrl":"https://doi.org/10.1002/art.43348","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"30 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769747","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":"Prognostic value of lupus anticoagulant and anti-β2 glycoprotein I antibody in adverse pregnancy outcomes.","authors":"Megumi Nonobe,Takahiro Otani,Hiroyuki Yoshihara,Shinobu Goto,Tamao Kitaori,Naomi Nishikawa,Yuichiro Fujieda,Tatsuya Atsumi,Mayumi Sugiura-Ogasawara","doi":"10.1002/art.43341","DOIUrl":"https://doi.org/10.1002/art.43341","url":null,"abstract":"OBJECTIVEInternational criteria for antiphospholipid syndrome (APS) include lupus anticoagulant (LA), anticardiolipin (aCL) immunoglobulin (Ig) G and IgM, and anti-β2-glycoprotein I (β2GPI) IgG and IgM. However, evidence supporting their prognostic value or treatment efficacy in improving live birth rates is limited. The Lancet series on miscarriage recommends testing only for LA and aCL, excluding β2GPI. We aimed to examine whether commercially available antiphospholipid antibody (aPL)-related tests have a prognostic value for obstetric APS.METHODSThis prospective cohort study enrolled 1,237 pregnant women between July 2021 and March 2024. Women using heparin, including those with an obstetric APS diagnosis before pregnancy, were excluded. Pregnancy outcomes were followed until December 2024. The aPL-related tests comprised LA (diluted activated partial prothrombin time and diluted Russell's viper venom time (LA-RVVT)), aCL IgG, IgM, anti-β2GPI IgG, IgM, anti β2GPI domain I IgG, phosphatidylserine-dependent anti-prothrombin (aPS/PT) IgG, IgM, protein S, and coagulation factor XII activity.RESULTSThe prevalence rates of early-onset preeclampsia, intrauterine fetal death (IUFD), and small gestational age were 1.4% (17), 0.7% (9), and 0.9% (11), respectively. Logistic regression analysis revealed that LA-RVVT and anti-β2GPI IgG were each predictor of early-onset preeclampsia and IUFD. The area under the curve for these conditions increased to about 0.8 when combined with a history of preeclampsia or IUFD, respectively.CONCLUSIONLA-RVVT, anti-β2GPI IgG, complications including hypertension and a history of IUFD were valuable in identifying obstetric APS. The variation in test results across facilities limits the ability to establish consistent prognostic or treatment value for each aPL.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"52 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769780","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":"Correction to \"Dysregulated NUB1 and Neddylation Enhances Rheumatoid Arthritis Fibroblast-Like Synoviocyte Inflammatory Responses\".","authors":"","doi":"10.1002/art.43345","DOIUrl":"https://doi.org/10.1002/art.43345","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"15 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777825","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":"Clinical Connections","authors":"","doi":"10.1002/art.43336","DOIUrl":"10.1002/art.43336","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"77 8","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.43336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740113","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":"Journal Club","authors":"","doi":"10.1002/art.43335","DOIUrl":"10.1002/art.43335","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"77 8","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.43335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740271","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.43336","DOIUrl":"10.1002/art.43336","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"77 8","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.43336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740339","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}