Arthritis & Rheumatology最新文献

{"title":"Association of Abatacept with Lower Mortality Risk Compared to Rituximab in Rheumatoid Arthritis-Associated Interstitial Lung Disease: An Emulated Target Trial.","authors":"Po-Cheng Shih,Shiow-Ing Wang,Qing-Wen Wang,James Cheng Chung Wei","doi":"10.1002/art.43332","DOIUrl":"https://doi.org/10.1002/art.43332","url":null,"abstract":"BACKGROUNDThe optimal treatment strategy for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains uncertain, and direct comparative data between biologics is limited. This study aimed to evaluate the effectiveness and safety of abatacept compared with rituximab in patients with RA-ILD.METHODSAn emulated target trial was designed using the TriNetX US Collaborative Network database, including patients with RA-ILD, diagnosed between 2007 and 2024. Propensity score matching (PSM) was used to balance baseline characteristics between the two treatment groups (abatacept and rituximab). The primary outcome was all-cause mortality, while secondary outcomes included respiratory events, medical utilization, and infection-related adverse events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to use Cox proportional hazards models.RESULTS1,615 patients per group were identified after matching for analysis. Abatacept was associated with a significantly lower risk of all-cause mortality compared with rituximab (HR 0.689, 95% CI 0.581-0.818) and a reduced risk of mechanical ventilation (HR 0.698, 95% CI 0.521-0.934). The subgroup analyses yielded consistent findings. Sensitivity analyses excluding patients with concomitant connective tissue diseases also demonstrated consistent results (mortality, HR 0.679, 95% CI 0.570-0.810), reinforcing the robustness of the findings.CONCLUSIONAbatacept was associated with a lower risk of mortality compared with rituximab in patients with RA-ILD. Because clinicians may preferentially reserve abatacept for less aggressive RA-ILD, residual confounding by indication cannot be excluded; thus, the association should not be interpreted as proof of causality. Prospective randomized trials are needed to confirm whether abatacept confers a true survival advantage.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"110 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677974","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":"Differences in IgG Sialylation Distinguish Asymptomatic from Symptomatic Anti-Nuclear Antibody Positive Individuals.","authors":"Carolina Muñoz-Grajales,Carmen C Ucciferri,Sindhu R Johnson,Zahi Touma,Zareen Ahmad,Dennisse Bonilla,Linda T Hiraki,Arthur Bookman,Joan E Wither","doi":"10.1002/art.43323","DOIUrl":"https://doi.org/10.1002/art.43323","url":null,"abstract":"OBJECTIVEThe transition from asymptomatic anti-nuclear antibody (ANA) positivity to systemic autoimmune rheumatic disease (SARD) is associated with increased production of pro-inflamamtory factors such as TNF-α. Here we investigate whether the relative absence of inflammation in asymptomatic ANA+ individuals (ANA+NS) results from a lack of circulating immune complexes (ICs) or from changes in the characteristics of the IgG auto-Abs produced.METHODSFlow cytometry was used to characterize circulating microparticles (MPs) in 18 healthy controls (ANA-HC), 31 ANA+NS and 51 symptomatic ANA+ patients. Differences in the ability of the total MPs, purified IgG-coated MPs, or aggregated IgG to elicit inflammation were investigated by co-culture with ANA-HC monocytes or monocyte derived dendritic cells (moDC), measuring cytokines in the supernatants. IgG sialylation was quantified by ELISA or lectin blotting using Sambucus Nigra Agglutinin, a sialic acid-binding lectin.RESULTSAll ANA+ individuals had higher numbers of total and IgG-coated MPs than ANA-HC. IgG sialylation was significantly reduced in SARD compared to ANA+NS and ANA-HC, and in ANA+NS who clinically progressed in the next 2 years compared to those who did not. moDC stimulated with IgG-coated MPs or aggregated IgG from SLE patients produced significantly more TNF-α than those from ANA+NS. The levels of TNF-α produced in culture supernatants and serum demonstrated a negative correlation with IgG sialylation.CONCLUSIONSThe absence of pro-inflammatory factors in ANA+NS does not result from a lack of circulating ICs, but instead may reflect differences in the extent of IgG sialylation in the ICs from ANA+NS as compared to SARD.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"29 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677975","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":"Late-Onset Spondylarthritis Presenting as Glucocorticoid-Resistant Polymyalgia Rheumatica: A hitherto underappreciated entity where TNF or IL-17 Blockade may have a Therapeutic Role.","authors":"Kerem Abacar,Gabriele De Marco,Jake Weddell,Katya Meridor,Tom Macleod,Andrew Scarsbrook,Kulveer Mankia,Edward Vital,Andrew Barr,Colin Pease,Helena Marzo-Ortega,Sarah L Mackie,Dennis McGonagle","doi":"10.1002/art.43320","DOIUrl":"https://doi.org/10.1002/art.43320","url":null,"abstract":"BACKGROUNDPolymyalgia rheumatica (PMR) is an age-related inflammatory disease with shoulder-hip girdle involvement. Magnetic resonance imaging (MRI) reveals extracapsular/entheseal soft tissue involvements in both PMR and spondyloarthritis (SpA) with sacroiliac joint and peri-entheseal spinal bone marrow oedema (BMO) being characteristic of SpA. Therefore, some shared anatomical topography might be expected to result in similar clinical features. Herein we describe the clinical and imaging features of SpA initially diagnosed as PMR.METHODSPatients followed at Leeds Teaching Hospitals NHS Trust with a diagnosis of psoriatic arthritis (PsA), or axial SpA (axSpA) were screened to identify those initially diagnosed with PMR from 2002 to 2024. Only those patients who retrospectively fulfilled the 2012 EULAR/ACR classification criteria or the Bird criteria for PMR were included. Clinical data relevant to initial PMR diagnosis, imaging features, follow-up and treatment data were collected, as well as radiographic or MRI features that established the final diagnosis.RESULTSThirty-one patients [median age in years (IQR): 62 (58-69); 17 females and 14 males] presenting with typical PMR shoulder/hip girdle pain were subsequently classified as SpA-spectrum disorders. The SpA diagnosis was made in 12 patients within three months of presentation, and in 19 patients during the remaining follow-up period [median (IQR): 3 (1-4) years]. Four of 27 tested patients were HLA-B27 positive. BMO on MRI was detected in the spine and/or sacroiliac joints in 20 of 25 imaged patients (80%) (sacroiliac joint: 17 patients [68%], spine: 15 patients [60%]). Clinical resolution with CRP normalisation occurred in 21 of 31 patients following initial glucocorticoid (GC) therapy, but 7 of these 21 initial responders experienced disease flares or CRP elevations. Therapy-wise, disease-modifying antirheumatic drugs (DMARDs) were used in 21 of 31 cases: 8 received conventional DMARDs, and 11 received biologic agents (eight anti-TNFs, three IL-17 inhibitors), while the remaining 10 patients were treated with 10 mg/day or less GC therapy.CONCLUSIONLate-onset SpA with PMR clinical presentations is characterised by failure to respond to or taper GC therapy and is often identified by SpA-specific osteitis patterns on MRI. We propose that a PMR-SpA overlap may account for biological therapy efficacy in steroid-refractory PMR.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"14 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677978","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 manifestations of VEXAS syndrome across a broad spectrum of UBA1 mutation burden","authors":"Meghan Anderson, Defne Ercelen, Ashley Richardson, Jung Kim, Rebecca I. Torene, Maria Sirenko, Jeremy S. Haley, Adam Cook, Wesley Hill, James Dove, Kyle Retterer, Eitan Carroll, David J. Carey, Samira Asgari, Douglas R. Stewart, David B. Beck","doi":"10.1002/art.43327","DOIUrl":"https://doi.org/10.1002/art.43327","url":null,"abstract":"ObjectiveVEXAS is a progressive systemic autoinflammatory disorder caused by somatic variants in <jats:italic>UBA1</jats:italic> in blood. Previous analyses have shown discordant disease penetrance. In this study, we examine the associations between demographic features and <jats:italic>UBA1</jats:italic> variant allele frequency (VAF) with disease manifestations.MethodsWhole exome sequencing data from 192,584 participants from Geisinger MyCode Community Health Initiative and Mount Sinai Bio<jats:italic>Me</jats:italic> Biobank were analyzed for disease‐causing variants in <jats:italic>UBA1</jats:italic>. Clinical manifestations were analyzed across individuals with <jats:italic>UBA1</jats:italic>‐variant.ResultsNine <jats:italic>UBA1</jats:italic> variants (VAF range 2.9%‐79%), in 23 participants (69.6% male) were identified. Cases with high VAF (&gt;20%) developed macrocytic anemia more often (87.5%) than patients with low VAF (≤ 20%) variants (27%; p=0.009). Specifically at the time of genetic testing, 87.5% of high VAF cases had macrocytic anemia, compared to 13.3% of low VAF cases (p=0.001). However, there was no significant difference in the development of anemia or thrombocytopenia (p=0.53). In two high VAF cases, macrocytosis developed more than 5 years prior to time of sample collection, followed by anemia approximately at the time of sample collection. In one low VAF case with other inflammatory symptoms, macrocytic anemia did not develop until 5 years after sample collection.ConclusionVEXAS syndrome disease severity and penetrance increase at higher VAFs. Low VAF cases demonstrate incomplete penetrance and those with disease tend to be milder. Females are enriched in lower VAFs and have milder symptoms suggesting a protective role against disease severity. Low VAF cases, especially ≤ 10%, can be initially asymptomatic and later develop disease.<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/art43327-toc-0001-m.png\"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"26 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669636","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":"ADAM9 promotes glycolysis in Th17 cells and autoimmunity through activation of IGF‐1 signaling","authors":"Kohei Karino, Masataka Umeda, Theodoros Vichos, Wenliang Pan, Michihito Kono, Maria G. Tsokos, George C. Tsokos","doi":"10.1002/art.43313","DOIUrl":"https://doi.org/10.1002/art.43313","url":null,"abstract":"ObjectivesIL‐17‐producing CD4<jats:sup>+</jats:sup> T helper (Th17) cells contribute to the pathogenesis of autoimmune diseases, including crescentic glomerulonephritis. Although a disintegrin and metalloproteinase 9 (ADAM9) has been reported to contribute to organ inflammation, the mechanism remains poorly understood. The goal of the current study was to investigate how ADAM9 alters T cell metabolism to promote the generation of Th17 cell differentiation.MethodsWe induced anti‐glomerular basement membrane (GBM) glomerulonephritis in <jats:italic>Adam9</jats:italic><jats:sup>+/+</jats:sup> and <jats:italic>Adam9</jats:italic><jats:sup>−/−</jats:sup> mice using sheep anti‐GBM IgG and compared disease severity. Glycolysis in Th17 cells was measured using a Seahorse XFp Extracellular Flux Analyzer, and metabolomic analysis was conducted on Th17 cells from both <jats:italic>Adam9</jats:italic><jats:sup>+/+</jats:sup> and <jats:italic>Adam9</jats:italic><jats:sup>−/−</jats:sup> mice. We measured the glucose transporter 1 (GLUT1) expression in Th17 cells from <jats:italic>Adam9</jats:italic><jats:sup>+/+</jats:sup> and <jats:italic>Adam9</jats:italic><jats:sup>−/−</jats:sup> mice and insulin like growth factor 1 (IGF‐1) treated Th17 cells. Finally, we assessed the protease activity of ADAM9 on IGF binding protein 4 (IGFBP4).ResultsMice deficient in ADAM9 had limited numbers of kidney‐infiltrating CD4+ T cells and suffered reduced kidney damage and inflammation following the injection of sheep anti‐GBM IgG. ADAM9 deficiency led to decreased GLUT1 expression and glycolysis in Th17 cells. Mechanistically, we found that ADAM9 cleaved IGFBP4 and enabled the release of IGF‐1, which enhanced the expression of GLUT1 and promoted glycolysis.ConclusionsBy cleaving IGFBP4, ADAM9 releases IGF‐1, which in turn upregulates GLUT1 expression and promotes glycolysis in Th17 cells. These findings suggest that targeting ADAM9 or blocking IGF‐1 should provide a therapeutic strategy for autoimmune diseases.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"47 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669643","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 cells and systemic sclerosis interstitial lung disease.","authors":"Nina Goldman,Voon Ong,Christopher Denton","doi":"10.1002/art.43326","DOIUrl":"https://doi.org/10.1002/art.43326","url":null,"abstract":"Interstitial lung disease is an important complication of systemic sclerosis (SSc-ILD) with high mortality and morbidity. Recent clinical studies in SSc-ILD have led to FDA-approved therapies in SSc-ILD. Importantly, evidence from these studies has been extrapolated to guide management of interstitial lung diseases of other systemic autoimmune rheumatic diseases. Pathogenesis of SSc-ILD involves interplay between fibroblasts and the innate and adaptive immune system. A central role for the B cell compartment is supported by clinical and translational studies. We use a case from our centre as a basis to discuss the pathogenesis of SSc-ILD, autoantibodies in SSc-ILD and the role of B cells in the disease. We go on to consider treatment options for the case, the decision-making algorithm for treatment and also risks associated with treatment.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"109 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669548","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":"Associations of specific pesticides and incident rheumatoid arthritis among female spouses in the Agricultural Health Study.","authors":"Christine G Parks,Darya Leyzarovich,Ghassan B Hamra,Karen H Costenbader,Dazhe Chen,Jonathan N Hofmann,Laura E Beane Freeman,Dale P Sandler","doi":"10.1002/art.43318","DOIUrl":"https://doi.org/10.1002/art.43318","url":null,"abstract":"OBJECTIVESGrowing evidence suggests farming and agricultural pesticide use may be associated with rheumatoid arthritis (RA), but few studies have examined specific pesticides and RA among farm women, who may personally use pesticides or be indirectly exposed. We investigated pesticide use and RA risk among female spouses of licensed pesticide applicators in the Agricultural Health Study.METHODSParticipants enrolled in 1993-1997 in North Carolina and Iowa (N=32,126). Incident RA cases were identified in follow-up questionnaires (1999-2021) and confirmed by medical records, relevant medication use, or Medicare claims data (1999-2016), or from Medicare claims if lacking questionnaire data on RA. Non-cases reported no RA and had no RA Medicare claims. Among those with complete covariate data (N=410 cases and 21,850 non-cases), we examined associations with pesticide classes and 32 specific pesticides (personal lifetime use reported at enrollment, updated in 1999-2003). We calculated odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, state, education, smoking pack-years smoking, body mass index, and correlated pesticides (rho>0.35).RESULTSIncident RA was associated with use of organochlorine [DDT (1.89;1.30-2.75), lindane (1.97;1.12-3.47)] and organophosphate insecticides [coumaphos (2.32;1.29-4.19), malathion (1.21;0.91-1.62)], the carbamate insecticide carbofuran (1.87;0.97-3.63), and permethrin or pyrethroid insecticides use on crops (1.56;0.92-2.64) or livestock (1.69;1.07-2.68). RA was not associated with using herbicides, except for metribuzin (1.88;0.94-3.79). The fungicides captan (1.78;1.13-2.83) and metalaxyl (2.49;1.41-4.40) were also associated with RA.DISCUSSIONThese findings indicate that persistent organochlorine insecticides and some pesticides also used in public health or residential settings may increase RA risk in women.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"15 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640107","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":"Features of Axial Spondyloarthritis in Two Multicenter Cohorts of Patients with Psoriasis, Uveitis, and Colitis Presenting with Undiagnosed Back Pain:comment on the article by Maksymowych et al.","authors":"W P Maksymowych, J Chan, Rgl Lambert","doi":"10.1002/art.43314","DOIUrl":"https://doi.org/10.1002/art.43314","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641319","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":"Diagnostic value of flame sign for acute gluteus medius calcific tendinitis.","authors":"De-An Qin,Qi-Jun An,Jie Yuan","doi":"10.1002/art.43321","DOIUrl":"https://doi.org/10.1002/art.43321","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"2 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640193","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":"Appendix Vasculitis in a Patient with Intestinal Behçet's Disease.","authors":"Hui Tian,Jing Ye,Zhao Li,Jingrun Zhao","doi":"10.1002/art.43331","DOIUrl":"https://doi.org/10.1002/art.43331","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"109 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640192","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}