Annals of the Rheumatic Diseases最新文献

{"title":"Rheumatoid arthritis patients harbour aberrant enteric bacteriophages with autoimmunity-provoking potential: a paired sibling study.","authors":"Fanlei Hu, Xin Li, Kai Liu, Yanpeng Li, Yang Xie, Chaonan Wei, Shuyan Liu, Jing Song, Ping Wang, Lianjie Shi, Chun Li, Jing Li, Liling Xu, Jimeng Xue, Xi Zheng, Mingxin Bai, Xiangyu Fang, Xu Jin, Lulu Cao, Pei Hao, Jing He, Jun Wang, Chiyu Zhang, Zhanguo Li","doi":"10.1136/ard-2024-225564","DOIUrl":"10.1136/ard-2024-225564","url":null,"abstract":"<p><strong>Objectives: </strong>Viruses have been considered as important participants in the development of rheumatoid arthritis (RA). However, the profile of enteric virome and its role in RA remains elusive. This study aimed to investigate the atlas and involvement of virome in RA pathogenesis.</p><p><strong>Methods: </strong>Faecal samples from 30 pairs of RA and healthy siblings that minimise genetic interferences were collected for metagenomic sequencing. The α and β diversity of the virome and the virome-bacteriome interaction were analysed. The differential bacteriophages were identified, and their correlations with clinical and immunological features of RA were analysed. The potential involvement of these differential bacteriophages in RA pathogenesis was further investigated by auxiliary metabolic gene annotation and molecular mimicry study. The responses of CD4⁺ T cells and B cells to the mimotopes derived from the differential bacteriophages were systemically studied.</p><p><strong>Results: </strong>The composition of the enteric bacteriophageome was distorted in RA. The differentially presented bacteriophages correlated with the immunological features of RA, including anti-CCP autoantibody and HLA-DR shared epitope. Intriguingly, the glycerolipid and purine metabolic genes were highly active in the bacteriophages from RA. Moreover, peptides of RA-enriched phages, in particular <i>Prevotella</i> phage and <i>Oscillibacter</i> phage could provoke the autoimmune responses in CD4⁺ T cells and plasma cells via molecular mimicry of the disease-associated autoantigen epitopes, especially those of Bip.</p><p><strong>Conclusions: </strong>This study provides new insights into enteric bacteriophageome in RA development. In particular, the aberrant bacteriophages demonstrated autoimmunity-provoking potential that would promote the occurrence of the disease.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1677-1690"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858891","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":"<i>Helicobacter pylori</i> upregulates PAD4 expression via stabilising HIF-1α to exacerbate rheumatoid arthritis.","authors":"Hui Wu, Hanmei Yuan, Jin Zhang, Taojun He, Yilin Deng, Ying Chen, Yunqi Zhang, Weisan Chen, Chao Wu","doi":"10.1136/ard-2023-225306","DOIUrl":"10.1136/ard-2023-225306","url":null,"abstract":"<p><strong>Objective: </strong><i>Helicobacter pylori</i> infection has been reported to aggravate rheumatoid arthritis (RA), but the relevant mechanism remains unclear. This study aimed to investigate the underlying pathogenic mechanism of <i>H. pylori</i> infection in the progression of RA.</p><p><strong>Methods: </strong>The Disease Activity Score (DAS-28) and serum anticitrullinated protein antibody (ACPA) levels were compared between <i>H. pylori</i>-negative and <i>H. pylori</i>-positive patients with RA. MH7A cells were stimulated with polyclonal ACPA purified from the peripheral blood of patients with RA. The citrullination levels were assessed by western blot in GES-1 cells and sera. ChIP, luciferase reporter assays, mass spectrometry and ELISA were applied to explore the molecular mechanism of <i>H. pylori</i> infection in RA progression.</p><p><strong>Results: </strong>The DAS-28 and ACPA levels of patients with RA in the <i>H. pylori</i>-positive group were significantly higher than those in the <i>H. pylori</i>-negative group. Polyclonal ACPA derived from <i>H. pylori</i>-positive patients promoted cell proliferation and induced secretion of IL-6 and IL-8. For the first time, we found that <i>H. pylori</i> infection induces cellular protein citrullination by upregulating protein arginine deiminase type 4 (PAD4). Furthermore, we confirmed a direct functional binding of hypoxia-inducible factor 1α on the <i>PADI4</i> gene promoter. We demonstrated that PAD4 interacts with and citrullinates keratin 1 (K1), and serum and synovial fluid levels of anti-Cit-K1 antibody were markedly increased in <i>H. pylori</i>-infected patients with RA.</p><p><strong>Conclusion: </strong>Our findings reveal a novel mechanism by which <i>H. pylori</i> infection contributes to RA progression. Therapeutic interventions targeting <i>H. pylori</i> may be a viable strategy for the management of RA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1666-1676"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896613","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":"Journey through discovery of 75 years glucocorticoids: evolution of our knowledge of glucocorticoid receptor mechanisms in rheumatic diseases.","authors":"Ann-Kathrin Eiers, Sabine Vettorazzi, Jan P Tuckermann","doi":"10.1136/ard-2023-225371","DOIUrl":"10.1136/ard-2023-225371","url":null,"abstract":"<p><p>For three-quarters of a century, glucocorticoids (GCs) have been used to treat rheumatic and autoimmune diseases. Over these 75 years, our understanding of GCs binding to nuclear receptors, mainly the glucocorticoid receptor (GR) and their molecular mechanisms has changed dramatically. Initially, in the late 1950s, GCs were considered important regulators of energy metabolism. By the 1970s/1980s, they were characterised as ligands for hormone-inducible transcription factors that regulate many aspects of cell biology and physiology. More recently, their impact on cellular metabolism has been rediscovered. Our understanding of cell-type-specific GC actions and the crosstalk between various immune and stromal cells in arthritis models has evolved by investigating conditional GR mutant mice using the Cre/LoxP system. A major achievement in studying the complex, cell-type-specific interplay is the recent advent of omics technologies at single-cell resolution, which will provide further unprecedented insights into the cell types and factors mediating GC responses. Alongside gene-encoded factors, anti-inflammatory metabolites that participate in resolving inflammation by GCs during arthritis are just being uncovered. The translation of this knowledge into therapeutic concepts will help tackle inflammatory diseases and reduce side effects. In this review, we describe major milestones in preclinical research that led to our current understanding of GC and GR action 75 years after the first use of GCs in arthritis.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1603-1613"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896616","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":"Efficacy and safety of therapies for Still's disease and macrophage activation syndrome (MAS): a systematic review informing the EULAR/PReS guidelines for the management of Still's disease.","authors":"Sara Bindoli, Arianna De Matteis, Stéphane Mitrovic, Bruno Fautrel, Loreto Carmona, Fabrizio De Benedetti","doi":"10.1136/ard-2024-225854","DOIUrl":"10.1136/ard-2024-225854","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse the efficacy and safety of treatments for Still's disease and macrophage activation syndrome (MAS).</p><p><strong>Methods: </strong>Medline, Embase and Cochrane Library were searched for clinical trials (randomised, randomised controlled trial (RCT), controlled and clinical controlled trial (CCT)), observational studies (retrospective, longitudinal observational retrospective (LOR), prospective and longitudinal observational prospective (LOP)) and systematic reviews (SRs), in which the populations studied were patients with Still's disease and MAS. The intervention was any pharmacological treatment (approved or under evaluation) versus any comparator drug or placebo, and as outcomes, any relevant efficacy and safety event. The risk of bias (RoB) was assessed with the Cochrane RoB and AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews-2, version 2) for SRs.</p><p><strong>Results: </strong>128 full texts were included: 25 RCTs, 1 CCT, 11 SRs published after 2013 and 91 LOP/LOR studies. In Still's disease, interleukin (IL)-1 inhibitors (IL-1i) and IL-6R inhibitors (IL-6i) were the most studied drugs. Two meta-analyses on RCTs showed an OR, to achieve an ARC50 response rate, of 6.02 (95% CI 2.24 to 21.36) and 8.08 (95% CI 1.89 to 34.57) for IL-1i and IL-6Ri, respectively. Retrospective studies showed that early initiation of IL-1i or IL-6i was associated with high rates of clinically inactive disease. In MAS, GCs were employed in all patients, often associated with ciclosporin and/or anakinra. Rates of complete response were reported, with a range from 53% to 100%. Emapalumab was the only drug tested in a CCT, with a complete response of 93%.</p><p><strong>Conclusion: </strong>IL-1i and IL-6Ri show the highest level of efficacy in the treatment of Still's disease. For MAS, IL-1 and interferon-γ inhibition appear to be effective on a background of high-dose glucocorticoids.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1731-1747"},"PeriodicalIF":3.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339933","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":"Multiorgan involvement and circulating IgG1 predict hypocomplementaemia in IgG4-related disease.","authors":"Guy Katz, Cory Perugino, Zachary S Wallace, Bohang Jiang, Thomas Guy, Grace A McMahon, Isha Jha, Yuqing Zhang, Hang Liu, Ana D Fernandes, Shiv S Pillai, John Patterson Atkinson, Alfred Hyoungju Kim, John H Stone","doi":"10.1136/ard-2024-225846","DOIUrl":"10.1136/ard-2024-225846","url":null,"abstract":"<p><strong>Objectives: </strong>Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease.</p><p><strong>Methods: </strong>We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia.</p><p><strong>Results: </strong>Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia.</p><p><strong>Conclusions: </strong>Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1773-1780"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854586","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":"Early identification of rheumatoid arthritis: does it induce treatment-related cost savings?","authors":"Elise van Mulligen, Maureen Rutten-van Mölken, Annette van der Helm-van Mil","doi":"10.1136/ard-2024-225746","DOIUrl":"10.1136/ard-2024-225746","url":null,"abstract":"<p><strong>Objective: </strong>Early diagnosis and treatment-start is key for rheumatoid arthritis (RA), but the economic effect of an early versus a later diagnosis has never been investigated. We aimed to investigate whether early diagnosis of RA is associated with lower treatment-related costs compared with later diagnosis.</p><p><strong>Methods: </strong>Patients with RA consecutively included in the Leiden Early Arthritis Clinic between 2011 and 2017 were studied (n=431). Symptom duration was defined as the time between symptom onset and first presentation at the outpatient clinic; early treatment start was defined as symptom duration <12 weeks. Information on disease-modifying anti-rheumatic drug use per patient over 5 years was obtained from prescription data from patient records. Prices were used from 2022 and 2012 (proxy of time of prescription) to study the impact of changes in drug costs. Autoantibody-positive and autoantibody-negative RA were studied separately because differences in disease severity may influence costs.</p><p><strong>Results: </strong>Within autoantibody-negative RA, costs were 316% higher in the late compared with the early group (β=4.16 (95% CI 1.57 to 11.1); €4856 vs €1159). When using 2012 prices, results were similar. For autoantibody-positive RA, costs were 19% higher in the late group (€9418 vs €7934, β=1.19, 0.57 to 2.47). This effect was present but smaller when using 2012 prices. Within patients with autoantibody-positive RA using biologicals, late treatment start was associated with 46% higher costs (β=1.46 (0.91 to 2.33)); higher costs were also seen when using 2012 prices.</p><p><strong>Conclusion: </strong>When RA is detected within 12 weeks after symptom onset, treatment-related costs were lower in both autoantibody-negative and autoantibody-positive RA. This study is the first to report how early diagnosis and treatment start impact treatment-related costs.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1647-1656"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632465","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":"Paul Hunter Plotz (1937-2024): renaissance rheumatologist, human rights advocate and mensch.","authors":"Frederick W Miller, John J O'Shea, Daniel L Kastner","doi":"10.1136/ard-2024-226596","DOIUrl":"10.1136/ard-2024-226596","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1644-1646"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339937","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":"News from EULAR.","authors":"","doi":"10.1136/ard-2023-225125","DOIUrl":"10.1136/ard-2023-225125","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"83 12","pages":"1800"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613751","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":"SerpinA3N limits cartilage destruction in osteoarthritis by inhibiting macrophage-derived leucocyte elastase.","authors":"Augustin Latourte, Sarah Jaulerry, Alice Combier, Chahrazad Cherifi, Yohan Jouan, Thierry Grange, Julien Daligault, Hang-Korng Ea, Martine Cohen-Solal, Eric Hay, Pascal Richette","doi":"10.1136/ard-2024-225645","DOIUrl":"10.1136/ard-2024-225645","url":null,"abstract":"<p><strong>Objectives: </strong>Inflammatory mediators such as interleukin 6 (IL-6) are known to activate catabolic responses in chondrocytes during osteoarthritis (OA). This study aimed to investigate the role of a downstream target gene of IL-6, the serine protease inhibitor SerpinA3N, in the development of cartilage damage in OA.</p><p><strong>Methods: </strong>RNA sequencing was performed in murine primary chondrocytes treated with IL-6, and identified target genes were confirmed in human and murine OA cartilage samples. Male cartilage-specific <i>Serpina3n</i>-deficient mice and control mice underwent meniscectomy (MNX) or sham surgery at 10 weeks of age. Intra-articular injections of SerpinA3N or sivelestat (an inhibitor of leucocyte elastase (LE), a substrate for SerpinA3N) were performed in wild-type mice after MNX. Joint damage was assessed 3-9 weeks after surgery by histology and micro-CT. The effect of sivelestat was assessed in cartilage explants exposed to macrophage-derived conditioned media.</p><p><strong>Results: </strong>RNA sequencing revealed that SerpinA3N is a major target gene of IL-6 in chondrocytes. The expression of SerpinA3N is increased in OA cartilage. Conditional loss of SerpinA3N in chondrocytes aggravated OA in mice, while intra-articular injection of SerpinA3N limited joint damage. Chondrocytes did not produce serine proteases targeted by SerpinA3N. By contrast, macrophages produced LE on IL-6 stimulation. Sivelestat limited the cartilage catabolism induced by conditioned media derived from IL-6-stimulated macrophages. Additionally, an intra-articular injection of sivelestat is protected against OA in the MNX model.</p><p><strong>Conclusions: </strong>SerpinA3N protects cartilage against catabolic factors produced by macrophages, including LE. SerpinA3N and LE represent new therapeutic targets to dampen cartilage damage in OA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1781-1790"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970470","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":"Serum from patients with idiopathic inflammatory myopathy induces skeletal muscle weakness.","authors":"Cecilia Leijding, Suchada Kaewin, Kristofer M Andreasson, Begum Horuluoglu, Angeles Shunashy Galindo-Feria, Eveline Van Gompel, Maryam Dastmalchi, Stefano Gastaldello, Helene Alexanderson, Ingrid E Lundberg, Daniel C Andersson","doi":"10.1136/ard-2024-225912","DOIUrl":"10.1136/ard-2024-225912","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1796-1797"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091709","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}