International Journal of Rheumatic Diseases最新文献

{"title":"A Bite of B Cells: The Potential Role of Bispecific T Cell Engager Therapy (BiTE) in Autoimmune Diseases","authors":"Jie-Fu Zheng, Yung-Heng Lee, Shih-Wen Kao, James Cheng-Chung Wei","doi":"10.1111/1756-185X.70252","DOIUrl":"https://doi.org/10.1111/1756-185X.70252","url":null,"abstract":"<p>Presently, systemic autoimmune rheumatic diseases are deemed to be incurable chronic conditions. In the current era of biologics and small molecule inhibitors between 5% and 20% of rheumatoid arthritis (RA) diagnoses are categorized as “difficult-to-treat RA” [<span>1</span>]. Despite the long-term survival rate of patients with systemic lupus erythematosus (SLE) improving in recent decades, for those with late-onset SLE, infections remain the primary cause of reduced long-term survival. Additionally, the presence of multiple comorbidities significantly limits the choice of medication, thus underscoring an urgent need for innovative therapeutic approaches [<span>2</span>].</p><p>Chimeric antigen receptor (CAR) T cell therapy may represent a revolutionary breakthrough in the treatment of autoimmune rheumatic diseases, which involves using retroviruses to insert genetically engineered genes into T cells, transforming them to express receptors that bind to specific cells and target them for destruction. The most notable success of CAR T cell therapy has been observed in lymphoma treatment, where CD19-targeted CAR T cells achieved complete remission in 40%–54% of cases involving relapsed or refractory aggressive B-cell lymphomas [<span>3</span>]. A research team from the University of Erlangen-Nuremberg in Germany was the first to explore the potential application of CAR T cell therapy to systemic autoimmune rheumatic diseases, such as SLE, with the hope of even achieving a cure in cases where traditional treatments have failed. According to a case series published by Fabian Müller and colleagues, CD19-targeted CAR T cell therapy has the potential to maintain disease remission in SLE for more than 2 years [<span>4</span>]. Successful cases have also been reported in idiopathic inflammatory myopathies (IIMs) and systemic sclerosis (SSc), as well as pediatric SLE [<span>5, 6</span>]. Recently, Wang et al. [<span>7</span>] applied allogeneic CAR T cells for the treatment of three patients with severe autoimmune diseases and published the initial positive outcomes. The success of allogeneic CAR T cells may significantly reduce the cost and time required for CAR T cell therapy.</p><p>Before undergoing CAR T cell therapy, patients must receive chemotherapy to eliminate existing T cells in the body to prevent them from attacking the CAR T cells, which can affect the therapy's effectiveness. Nonetheless, this therapeutic modality may provoke cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome due to CAR T cell hyperactivation. Additionally, the depletion of most B cells targeted by CD19-directed CAR T cells may lead to insufficient antibody production and increased susceptibility to recurrent infections, although this issue can be mitigated with immunoglobulin supplementation. For individuals with SLE, particularly those with severe disease unresponsive to standard therapies, the potential advantages of CD19-targeted CAR T","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185X.70252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WTAP's Dual Role in Disease: Orchestrating Inflammation in Rheumatoid Arthritis and Challenging Renal Clear Cell Carcinoma Outcomes","authors":"Chen-Yueh Wen, Po-Hung Chen, Chien-Wei Huang, Yen Chin, Chia-Jung Li","doi":"10.1111/1756-185X.70248","DOIUrl":"https://doi.org/10.1111/1756-185X.70248","url":null,"abstract":"<p>The study by Wang et al. titled “WTAP-Mediated m6A Modification of TRAIL-DR4 Suppresses MH7A Cell Apoptosis” highlights the critical role of Wilms tumor 1-associating protein (WTAP), a regulatory component of the N6-methyladenosine (m6A) methyltransferase complex, forms a functional unit with METTL3 and METTL14 to mediate m6A deposition [<span>1</span>]. WTAP promotes mRNA destabilization of TNF-related apoptosis-inducing ligand death receptor 4 (TRAIL-DR4), thereby inhibiting apoptosis and contributing to synovial hyperplasia and persistent inflammation. These findings are consistent with earlier reports demonstrating WTAP's role in inflammatory regulation through m6A-dependent mechanisms, including modulation of cytokine expression in activated macrophages [<span>2</span>]. Building on these foundations, our current investigation expands the scope of WTAP's functional landscape by exploring its relationship with the tumor immune microenvironment, in parallel with its role in inflammatory signaling. This integrated approach is crucial, given the mechanistic overlaps between chronic inflammation and tumorigenesis [<span>3</span>].</p><p>Our study utilized a comprehensive multi-omics approach to elucidate the impact of WTAP expression on genetic landscapes, biological processes, and drug responses in Kidney Renal Clear Cell Carcinoma (KIRC), leveraging data from the TCGA database. We extracted WTAP expression profiles from KIRC patients and visualized the top 20 affected genes using a waterfall plot (Figure 1A). The genetic alterations included oncogenes, tumor suppressor genes, splice site mutations, and frameshift variants, providing a broad genomic context. Comparative analysis of mRNA (Figure 1B) and protein (Figure 1C) expression levels between normal and KIRC tissues revealed a significant reduction in WTAP expression in tumor samples, consistent across TCGA and proteomic datasets.</p><p>Further prognostic analysis using Kaplan–Meier curves demonstrated that low WTAP expression in KIRC is associated with poor overall survival and progression-free survival (Figure 1D,E). This suggests that WTAP's function may be highly tissue- and disease-specific, differing from its anti-apoptotic and anti-inflammatory role in RA. To explore the immunological underpinnings, we assessed T-cell interactions across six independent databases, consistently identifying a positive correlation between WTAP expression and T-cell activation (Figure 1F). We extended our analysis to T-cell-related biological processes, evaluating activation, homeostasis, proliferation, and chemotaxis in KIRC patients stratified by WTAP expression levels (Figure 1G). This contrasts with the MH7A cell model, where WTAP-mediated m6A modification of TRAIL-DR4 inhibits apoptosis and modulates inflammation. Additionally, we interrogated the PRISM Pharmacogenomic Database to assess drug sensitivity and resistance, identifying 20 drugs where high WTAP expression predicted increased sensitivi","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185X.70248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPA and EGPA: Comparison of the 1990 ACR Criteria With the 2022 ACR/EULAR Criteria in a Monocentric Cohort of Patients","authors":"Lorenzo Puccetti, Francesco Ferro, Michele Moretti, Ilaria Puxeddu, Chiara Baldini, Paola Migliorini","doi":"10.1111/1756-185X.70222","DOIUrl":"https://doi.org/10.1111/1756-185X.70222","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Predictive Factors of Difficult-To-Manage Axial Spondyloarthritis: Results From the KOBIO Registry","authors":"Kyung-Ann Lee, Heeyeon Lee, Hyun-Sook Kim","doi":"10.1111/1756-185X.70242","DOIUrl":"https://doi.org/10.1111/1756-185X.70242","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEXAS Syndrome: Phenotype Alteration in the Long-Term Disease Duration","authors":"Yue Sun, Zhuoya Zhang, Hong Wang, Yun Zhu, Lingyun Sun","doi":"10.1111/1756-185X.70244","DOIUrl":"https://doi.org/10.1111/1756-185X.70244","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil Z Is a Novel Marker to Differentiate Disease Flares From Bacterial Infections in Febrile SLE Patients","authors":"Kishan Majithiya,&nbsp;Komal Singh,&nbsp;Pankti Mehta,&nbsp;Chengappa Kavadichanda,&nbsp;M. S. Gayathri,&nbsp;Deepika Kounassegarane,&nbsp;Ranjan Gupta,&nbsp;Seema Sharma,&nbsp;Able Lawrence,&nbsp;Amita Aggarwal","doi":"10.1111/1756-185X.70243","DOIUrl":"https://doi.org/10.1111/1756-185X.70243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim and Objectives</h3>\u0000 \u0000 <p>To assess the role of newer biomarkers like neutrophil Z, myeloid-related protein 8/14 (MRP 8/14), IL-6, sCD14, and neutrophil CD64 (nCD64) to distinguish flare from infection in febrile lupus patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective multicentric observational study to determine the etiology of fever in febrile lupus patients, in addition to routine tests, serum procalcitonin, neutrophil X, neutrophil Y, and neutrophil Z were done. sCD14, MRP8/14, and IL-6 were done by ELISA. nCD64 expression was measured by flow cytometry. All these biomarkers were assessed individually and in combination to see their ability to distinguish between infection and lupus flare.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 159 febrile SLE patients, there were 55 infections, 65 disease flares, 38 flares and infections combined, and 1 malignancy. Patients with bacterial infections had a higher CRP, procalcitonin, neutrophil-to-lymphocyte ratio, Neutrophil Z, sCD14 levels, and neutrophil CD64 expression. While patients with flares had lower C3, C4, and higher anti-DsDNA antibody levels. IL-6 and MRP8/14 levels were similar in both groups. Combination of neut-Z with C3 or anti-dsDNA antibody could discriminate between flare and infection with AUC 0.88 (0.80–0.96) and 0.86 (0.78–0.95). Addition of TLC or procalcitonin or nCD64 MFI to these scores improved them marginally. Though composite scores with CRP and anti-dsDNA/procalcitonin also performed well but these were inferior to neutrophil Z-based composite models. These results were consistent in sensitivity analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Neutrophil Z, complement C3, anti-dsDNA antibody levels, and TLC or procalcitonin-based composite score are good tools to differentiate between infection and flare in a febrile lupus patient. Serum MRP 8/14, IL-6, sCD14, and nCD64 did not perform well. Simple biomarkers such as neut-Z should be investigated further in SLE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Phosphorylation Pathway in Ankylosing Spondylitis: Multi-Omics Analysis and Machine Learning","authors":"Yuling Chen,&nbsp;Yuan Xu,&nbsp;Shuangyan Cao,&nbsp;Qing Lv,&nbsp;Yuanchun Ye,&nbsp;Jieruo Gu","doi":"10.1111/1756-185X.70175","DOIUrl":"https://doi.org/10.1111/1756-185X.70175","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, characterized by immune microenvironment dysregulation and elevated cytokines like TNF-α and IL-17. Mitochondrial oxidative phosphorylation (OXPHOS), crucial for immune cell function and survival, is implicated in AS pathogenesis. This study explores OXPHOS-related mechanisms in AS, identifies key genes using machine learning, and highlights potential therapeutic targets for precision medicine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells (PBMCs) bulk transcriptomic and single-cell RNA sequencing (scRNA-seq) data from AS patients were analyzed to investigate the role of the OXPHOS pathway in AS. Weighted gene co-expression network analysis (WGCNA) was performed to identify key gene modules associated with OXPHOS. Machine learning techniques, including support vector machine with recursive feature elimination (SVM-RFE), random forest, and least absolute shrinkage and selection operator (LASSO), were applied to identify significant AS-related genes. Real-time PCR (RT-PCR) was used to quantify gene expression, examine their patterns in specific cell subtypes, and explore their functional implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pathway enrichment analysis identified OXPHOS as a significantly enriched pathway distinguishing AS patients from healthy controls, with high normalized enrichment scores and significant group separation in principal component analysis. ScRNA-seq revealed significantly higher OXPHOS scores in AS patients, especially in dendritic cells (DCs) and monocytes, highlighting cell type-specific dysregulation. WGCNA identified two key gene modules (MEyellow and MEtan) that are closely associated with OXPHOS. Three hub genes—<i>LAMTOR2</i>, <i>APBB1IP</i>, and <i>DGKQ</i>—were screened using machine learning methods and validated by RT-PCR and scRNA-seq. Among them, <i>LAMTOR2</i> was significantly more highly expressed in patients with AS, and functional analyses showed that it plays a role in promoting TH17 cell differentiation, which highlights its potential as a therapeutic target for ankylosing spondylitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This multi-omics study provides valuable insights into the complex interplay between OXPHOS and AS. The identified genes, particularly <i>LAMTOR2</i>, serve as potential therapeutic targets, contributing to our understanding of AS mechanisms and paving the way for precision medicine in AS treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Periprosthetic Joint Infection Rate Following Total Knee Arthroplasty in Rheumatoid Arthritis Patients: Insights From a Japanese Nationwide Medical Claims Database Study","authors":"Yu Mori,&nbsp;Kunio Tarasawa,&nbsp;Hidetatsu Tanaka,&nbsp;Ryuichi Kanabuchi,&nbsp;Hiroshi Hatakeyama,&nbsp;Naoko Mori,&nbsp;Kiyohide Fushimi,&nbsp;Toshimi Aizawa,&nbsp;Kenji Fujimori","doi":"10.1111/1756-185X.70249","DOIUrl":"https://doi.org/10.1111/1756-185X.70249","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Advances in pharmacological treatments have reduced joint deformities in rheumatoid arthritis (RA), leading to a decline in total knee arthroplasty (TKA) among RA patients. However, RA remains associated with higher risks of postoperative complications. This study compares postoperative complications during hospitalization in patients with RA and osteoarthritis (OA) undergoing TKA in Japan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort study utilized data from the Japanese Diagnosis Procedure Combination database from April 2016 to March 2023. Patients who underwent TKA were identified, and propensity score (PS) matching was performed to balance age, sex, body mass index, simultaneous surgeries, and comorbidities, resulting in 9048 matched pairs. Outcomes included periprosthetic joint infections (PJI), cognitive dysfunction, deep vein thrombosis (DVT), pulmonary embolism (PE), and periprosthetic fractures. Statistical analyses were conducted using multivariate logistic regression with a significance threshold of <i>p</i> &lt; 0.01.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RA patients had higher risks of PJI (odds ratio [OR]: 1.473, 95% CI: 1.134–1.912, <i>p</i> = 0.004) and postoperative cognitive dysfunction (OR: 1.721, 95% CI: 1.190–2.488, <i>p</i> = 0.004) compared to OA patients. In contrast, no significant differences were observed in the incidence of DVT, PE, or periprosthetic fractures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RA patients undergoing TKA are at increased risk of PJI and cognitive dysfunction, highlighting the need for tailored perioperative management. These findings provide important insights into optimizing outcomes for RA patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Surgery for the Patient With Systemic Lupus Erythematosus Complicated by Type A Aortic Dissection","authors":"Kaiyue Sun,&nbsp;Ruyuan Wei,&nbsp;Fushun Lin,&nbsp;Dexin Zhang,&nbsp;Kai Liu","doi":"10.1111/1756-185X.70245","DOIUrl":"https://doi.org/10.1111/1756-185X.70245","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of Infection-Related Hospitalization and the Impact of Multidisciplinary Care in ANCA-Associated Vasculitis: A Retrospective Cohort","authors":"Emily K. Yeung,&nbsp;A. Richard Kitching,&nbsp;Michael Gingold,&nbsp;Kevan R. Polkinghorne,&nbsp;Jessica Ryan","doi":"10.1111/1756-185X.70139","DOIUrl":"https://doi.org/10.1111/1756-185X.70139","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}