RMD Open最新文献

{"title":"Serum biochemical marker of synovial tissue turnover, C1M, predicts radiological progression in early rheumatoid arthritis.","authors":"Patrick Garnero, Sofie Falkenløve Madsen, Florent Eymard, Jérémie Sellam, Roland Chapurlat, Anne-C Bay-Jensen","doi":"10.1136/rmdopen-2025-005501","DOIUrl":"10.1136/rmdopen-2025-005501","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether serum C1M and C2M, biochemical markers of synovial and cartilage tissue destruction, were associated with progression of joint damage in patients with early arthritis.</p><p><strong>Methods: </strong>813 early arthritis patients (<6 months of symptoms, 82% with rheumatoid arthritis, 18% undifferentiated arthritis) from the prospective ESPOIR study were followed for 5 years. Radiographic progression was assessed using the van der Heijde Sharp score, and progression was defined as an increase of 1 or 5 unit(s) between baseline and 1 year or 5 years. Associations between baseline C1M and C2M and progression were assessed by logistic regression.</p><p><strong>Results: </strong>Increased baseline continuous serum C1M levels were associated with the risk of progression at 1 year, after adjustment for age, gender and body mass index (BMI). Patients with levels in the highest quartile of C1M had an OR (95% CI) of total joint damage progression of 2.75 (1.70-4.45) compared with patients in the lowest quartile. When disease activity score 28, C reactive protein and anticyclic citrullinated peptide 2 antibodies positivity were included in the model, high C1M remained significantly associated with progression with an OR (95% CI) of 2.12 (1.06-4.23). At 5 years, C1M was significantly associated with the risk of total joint damage progression after adjustment for age, gender and BMI. There was no significant association of C2M with progression at 1 year or 5 years.</p><p><strong>Conclusions: </strong>High baseline serum C1M, but not C2M, is associated with increased radiographic progression in early arthritis, independently of classical risk factors. C1M, in conjunction with other risk factors, may help identify patients at higher risk of joint damage.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning using genotype and gene-expression data identifies alterations of genes involved in infection susceptibility, antigen presentation and cytokine signalling as key contributors to JIA risk prediction.","authors":"Nicholas Pudjihartono, Daniel Ho, Justin Martin O'Sullivan","doi":"10.1136/rmdopen-2025-005737","DOIUrl":"10.1136/rmdopen-2025-005737","url":null,"abstract":"<p><strong>Background: </strong>Previous genome-wide association studies (GWAS) have identified numerous genetic loci associated with juvenile idiopathic arthritis (JIA). However, the functional impact of these variants-particularly on tissue-specific gene expression-and which regulatory interactions make the greatest relative contribution to JIA risk remain unclear. Identifying these key single-nucleotide polymorphism (SNP)-gene-tissue combinations can help prioritise targets for future functional studies and therapeutic interventions.</p><p><strong>Method: </strong>We performed two-sample Mendelian randomisation (2SMR) using spatial expression quantitative trait loci (eQTLs) from nine tissue-specific gene-regulatory networks as instrumental variables (IVs). We also identified JIA-associated SNPs from previous GWAS and mapped their spatial eQTL effects across 49 human tissues. These SNP sets were then used as features in a Lasso-regularised logistic regression model to predict JIA disease status. The model weight magnitudes served as proxies for each SNP's contribution to JIA risk. We evaluated the robustness of our model's feature ranking across 50 cross-validation runs.</p><p><strong>Results: </strong>The top-ranked SNPs included rs7775055, which tags the human leukocyte antigen (HLA) class II haplotype <i>DRB1*0801-DQA1*0401-DQB1*0402</i>, and rs6679677, a non-coding variant that is in 100% linkage with with a coding variant in <i>PTPN22</i>. IVs for genes implicated in infection-related immune processes (eg, <i>MSH5</i>, <i>MICA</i> and <i>LINC01149</i>) also made significant contributions to JIA risk. We additionally identified a spatial eQTL (rs10849448) that upregulated the cytokine signalling gene <i>LTBR</i> across all 49 tissues. Overall, our model highlighted the roles of genes involved in antigen presentation, infection susceptibility and cytokine signalling.</p><p><strong>Conclusion: </strong>By applying a machine learning approach to rank SNP-gene-tissue contributions to JIA risk, our findings offer insights into the genetic mechanisms underlying JIA pathogenesis. Future experimental validation could facilitate new therapeutic targets for the treatment or prevention of JIA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clusters in paediatric Behçet's disease: a multicentre international study.","authors":"Ummusen Kaya Akca, Farhad Shahram, Erdem Karabulut, Massoomeh Akhlaghi, Seyedeh Tahereh Faezi, Ozlem Akgun, Mustafa Çakan, Esra Esen, Caterina Matucci-Cerinic, Ruya Torun, Erbil Unsal, Marco Gattorno, Nuray Aktay Ayaz, Ayşenur Paç Kısaarslan, Betul Sozeri, Ezgi Deniz Batu, Isabelle Koné-Paut, Seza Ozen","doi":"10.1136/rmdopen-2024-005335","DOIUrl":"10.1136/rmdopen-2024-005335","url":null,"abstract":"<p><strong>Objectives: </strong>Clinical features of Behçet's disease (BD) exhibit significant variability, not only from patient to patient but also according to gender and geographical region. This study aims to describe the clinical characteristics, identify distinct clusters in a large cohort of paediatric BD patients and compare the clinical manifestations of patients across three geographical regions: Turkey, Europe and Iran.</p><p><strong>Method: </strong>Patients with paediatric-onset BD (<18 years of age) from Turkey, Iran and European countries (France and Italy) were retrospectively evaluated. A follow-up period of at least 6 months was required for inclusion.</p><p><strong>Results: </strong>The study included 600 patients (297 females, 49.5%), with cases from Turkey (n=231), Iran (n=306), France (n=44) and Italy (n=19). The most common presentations were mucocutaneous involvement (97.5%), followed by ocular (48.0%), musculoskeletal (43.2%), neurological (11.8%), vascular (11.5%), gastrointestinal (9.0%) and cardiac (2.0%) involvement. Ocular involvement was more prevalent in Iran, gastrointestinal involvement in Europe, and musculoskeletal and vascular involvement in Turkey compared with the other geographical regions. Seven distinct clusters of paediatric BD as vascular (cluster 1 (C1)), mucocutaneous only (C2), ocular (C3), gastrointestinal (C4), mixed (C5), neurologic and ocular (C6), and mucocutaneous-musculoskeletal cluster (C7) were identified, although there was some overlap in system involvements.</p><p><strong>Conclusions: </strong>Our study supports the notion that BD may tend to present in certain clusters in children as well. Since BD is a complex disease with a multifactorial aetiology, involving the interaction of pathogenic pathways, classification of clusters presents a significant challenge. We have also shown that certain clinical features vary among geographical regions.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive immune responses to SARS-CoV-2 in DMARD-treated patients with chronic inflammatory rheumatisms.","authors":"Maxime Beretta, Emmanuel Martin, Olivier Fogel, Clementina López-Medina, Cyril Planchais, Thomas Bruneau, Pedro Goncalves, Jerome Avouac, Francis Berenbaum, Jérémie Sellam, Bruno Fautrel, Jacques Morel, Beatrice Parfait, James P Di Santo, Sylvie Behillil, Sylvie van der Werf, Helene Péré, Sylvain Latour, Hugo Mouquet, Corinne Miceli-Richard","doi":"10.1136/rmdopen-2025-005673","DOIUrl":"10.1136/rmdopen-2025-005673","url":null,"abstract":"<p><strong>Background: </strong>Patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are at an increased risk for infection related to the use of immunomodulatory therapies (ITs). The objective of this study is to assess the impact of ITs on the adaptive immune responses to SARS-CoV-2.</p><p><strong>Methods: </strong>The study population comprised 94 patients (48 SpA; 46 RA; mean age of 53±14 years) with a confirmed SARS-CoV-2 infection. 20 age-matched individuals (50±17 years), corresponding to the patients' household contacts infected at the same time, were included as the control population. Patients were stratified by treatment groups: methotrexate (MTX)/sulfasalazine (n=17/2), anti-TNF (n=24), anti-TNF+MTX (n=23), RTX (N=11), anti-IL17 (n=7) and others (n=11). The study compared the viral loads in plasma, stools and nasal swabs and the SARS-CoV-2-specific humoral and cellular immune responses (antibodies, B and T lymphocytes) following SARS-CoV-2 infection.</p><p><strong>Results: </strong>Viral persistence was not observed in the blood, nasopharynx and stools of patients undergoing ITs. Overall, the SARS-CoV-2-specific humoral and T-cell responses were preserved. Patients receiving RTX showed significantly lower IgA and IgG responses to SARS-CoV-2 compared with other treatment groups. Most patients, including RTX recipients, exhibited significant CD4+T cell responses. However, RTX therapy was associated with reduced SARS-CoV-2-specific activated CD8+T cells. A correlation was observed between humoral immune parameters and CD8⁺ T cell activation.</p><p><strong>Conclusions: </strong>While most patients demonstrated the capacity to mount an immune response to SARS-CoV-2, treatment with RTX impacted both humoral and CD8+cell responses. Developing vaccines that elicit robust CD8+T cell responses could offer benefits to individuals undergoing ITs for inflammatory rheumatic diseases.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in nailfold capillaroscopy findings between limited and diffuse cutaneous systemic sclerosis: a detailed analysis.","authors":"Ana Margarida Correia, Rosanna Campitiello, Carmen Pizzorni, Emanuele Gotelli, Alberto Sulli, Sabrina Paolino, Vanessa Smith, Maurizio Cutolo","doi":"10.1136/rmdopen-2025-005716","DOIUrl":"10.1136/rmdopen-2025-005716","url":null,"abstract":"<p><strong>Objective: </strong>To investigate and distinguish detailed nailfold videocapillaroscopy (NVC) findings in patients with limited (lcSSc) and diffuse (dcSSc) cutaneous systemic sclerosis (SSc).</p><p><strong>Methods: </strong>A total of 157 patients was recruited, 100 with lcSSc, 27 with dcSSc and 30 with primary Raynaud phenomenon (pRP). The NVC SSc pattern and the absolute number of capillaries (per linear millimetre) were performed at the first NVC analysis. 'Early'/'Active' NVC status (capillary dilations, microhaemorrhages and giant capillaries) and 'Late' NVC status (number of capillaries, altered microvascular architecture and abnormal capillary shapes) were scored.</p><p><strong>Results: </strong>A statistically significant difference in the absolute number of capillaries between patients with lcSSc, dcSSc and pRP was found (p<0.001). Capillary number loss was present in both SSc subgroups and it was significantly higher in patients with dcSSc compared with lcSSc (4.89±1.53 vs 6.18±1.75, p<0.001). A significantly higher 'Late' NVC status score was observed in patients with dcSSc (p<0.001), including lower capillary density (p<0.001), altered shapes (p<0.001) and presence of abnormal shapes (p=0.005). Correlations showed that higher modified Rodnan Skin Score is associated with decreased capillary number and higher 'Late' NVC status score (p<0.001). Additionally, a statistically significant association was established between 'Late' SSc pattern and dcSSc (p=0.004) and between 'Early' SSc pattern and lcSSc (p=0.010). The absolute capillary number was normal and significantly higher in patients with pRP (p<0.001) than in all patients with SSc.</p><p><strong>Conclusions: </strong>The current investigation underlines the importance of NVC detailed analysis and scoring in discriminating the severity of microvascular damage between lcSSc and dcSSc.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and prevalence of ANCA-associated vasculitis in Oslo, Norway, applying different criteria-based case definitions: a population-based cohort study.","authors":"Karin R Kilian, Cathrine Brunborg, Sigrun Skaar Holme, Garen Torhild, Ragnar Gunnarsson, Øyvind Molberg","doi":"10.1136/rmdopen-2025-005526","DOIUrl":"10.1136/rmdopen-2025-005526","url":null,"abstract":"<p><strong>Objective: </strong>To provide complete data on the incidence and prevalence of antineutrophil cytoplasmic antibody-associated vasculitides (AAV) over the years 2000-2016 in the Oslo area, Norway, with 528 924 adults (aged 18+) in 2016.</p><p><strong>Methods: </strong>From administrative databases, we identified all cases with International Classification of Disease, 10th Revision (ICD-10) codes indicative of necrotising small vessel vasculitis during 2000-2016 in the Oslo area. We manually chart reviewed every case identified through the ICD-10 search to confirm (or reject) a clinical AAV diagnosis. Cases with confirmed clinical AAV were classified by the European Medicine Agency (EMA) algorithm and the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR 2022) classification criteria.</p><p><strong>Results: </strong>Among 469 cases with an ICD-10 code indicative of small vessel vasculitis, chart review confirmed AAV in 133 cases with 97 having new onset during the study. Of these 97 incident cases, 57 (60%) were classified as granulomatosis with polyangiitis (GPA), 29 (31%) as microscopic polyangiitis (MPA) and 9 (9%) as eosinophilic granulomatosis with polyangiitis (EGPA) per ACR/EULAR 2022 criteria, while 2 remained unclassified. There was an 11% discordance in AAV case classification between the 2022 criteria and the EMA algorithm. The mean annual incidence of AAV in adults was 12.2 per million (7.3 for GPA, 3.7 for MPA and 1.2 for EGPA). Across the study period, incidence rates increased numerically, and prevalence peaked at 143.7 AAV cases/million adults in 2016.</p><p><strong>Conclusion: </strong>This population-based study adds new evidence that AAV increases in Europe and indicates that using the ACR/EULAR 2022 criteria shifts cases from GPA to MPA relative to the EMA algorithm, affecting epidemiology estimates.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of patient-reported outcome measures for dactylitis, psoriatic skin and nail disease, and uveitis in patients with psoriatic arthritis in routine care.","authors":"Louise Majormoen Nielung, Lene Dreyer, Lone Skov, Merete Lund Hetland, Bente Glintborg","doi":"10.1136/rmdopen-2025-005705","DOIUrl":"10.1136/rmdopen-2025-005705","url":null,"abstract":"<p><strong>Background: </strong>In routine care, Danish patients with psoriatic arthritis are monitored in the DANBIO registry. In March 2022, patient-reported outcome measures (PROMs) on selected non-musculoskeletal manifestations (NMM) were implemented.</p><p><strong>Aim: </strong>To validate PROMs for current dactylitis, skin and nail psoriasis, and recent uveitis in patients with psoriatic arthritis.</p><p><strong>Methods: </strong>Adaptive cross-sectional study. Patients in the rheumatologic clinic answered PROMs with 'yes'/'no'/'do not know' and assessed the extent of skin psoriasis and number of dactylitis-affected digits in DANBIO. PROM entries were compared with the physician's assessments (physical examination, review of patient file), with the physician being the gold standard. With 134 patients included, 20% had incorrectly reported dactylitis; therefore, a dactylitis photo was added to the PROM. Sensitivity, specificity, positive and negative predictive values, accuracy and Cohen's kappa were calculated. Level of agreement for dactylitis count was explored by Bland-Altman plot. From patient 200, the physician was blinded to PROs.</p><p><strong>Results: </strong>We included 300 patients (51% female, median age=55 years), with a median disease duration of 8 years, where 43% received biologic treatment. According to the physician's assessment, 41 (14%) patients had current dactylitis, 164 (55%) psoriasis, 163 (54%) nail psoriasis and 3 (1%) recent uveitis. For the dactylitis PROM, the sensitivity/specificity/Cohen's kappa was 0.89/0.81/0.57, psoriasis 1.0/0.94/0.95, nail psoriasis 0.76/0.94/0.66 and uveitis 1.00/0.99/0.59. Agreement on psoriasis extent was 90%. Patient-reported dactylitis count was on average 1.0 unit higher than physician-reported but decreased to 0.7 after adding the dactylitis photo. Results were similar irrespective of blinding.</p><p><strong>Conclusion: </strong>Patients reliably self-report dactylitis, psoriasis, and uveitis and the PROMs are valuable for monitoring NMMs in routine care.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis.","authors":"Laura Cuesta-López, Iván Arias-de la Rosa, Jesús Eduardo Martín-Salazar, Antonio Manuel Barranco, Lourdes Ladehesa-Pineda, Miriam Ruiz-Ponce, María Ángeles Puche Larrubia, Carlos Pérez-Sánchez, Pedro Seguí, Rafaela Ortega, Jerusalem Calvo, María Carmen Ábalos-Aguilera, Desirée Ruiz-Vilchez, Elena Moreno-Caño, Pedro Ortiz-Buitrago, Chary Lopez-Pedrera, Alejandro Escudero-Contreras, Eduardo Collantes, Clementina López-Medina, Nuria Barbarroja","doi":"10.1136/rmdopen-2025-005746","DOIUrl":"10.1136/rmdopen-2025-005746","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the impact of sustained C reactive protein (CRP) elevation on cardiovascular (CV) risk factors, particularly endothelial dysfunction and atherosclerosis, in axial spondyloarthritis (axSpA) patients and to explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>245 axSpA patients were enrolled. Carotid intima-media thickness (CIMT) and microvascular endothelial function (post-ischaemic reactive hyperaemia) were measured. Retrospective CRP measurements from the past 5 years classified patients as having sustained high CRP if >50% of readings were elevated. Serum levels of 184 inflammation and CV disease-related proteins were analysed using a proximity extension assay, and in vitro studies were conducted in human umbilical vein endothelial cells.</p><p><strong>Results: </strong>40% of axSpA patients had sustained CRP elevation, showing increased metabolic comorbidities, higher prevalence of atherosclerotic plaques and worse microvascular endothelial function compared with those with intermittent CRP elevations. Proteomic analysis identified 10 altered proteins, with interleukin 6 (IL-6) and CUB domain-containing protein 1 (CDCP-1) linked to endothelial dysfunction, higher CIMT and metabolic disturbances. Paraoxonase 3 (PON-3), the only downregulated protein, showed anti-inflammatory, antioxidant and antiatherogenic properties, restoring endothelial function in vitro. CDCP-1 was associated with atherosclerotic plaques and promoted endothelial adhesion, oxidative stress and inflammation in vitro. Anti-TNF-α therapy reduced inflammatory markers, complement components and the atherogenic index, while increasing high density lipoprotein, apolipoprotein A and PON-3 levels and decreasing IL-6 and CDCP-1 levels.</p><p><strong>Conclusions: </strong>Sustained CRP elevation in axSpA is strongly linked to increased CV risk, endothelial dysfunction and atherosclerosis. IL-6, CDCP-1 and PON-3 emerge as key mediators connecting inflammation to CV risk. Anti-tumour necrosis factor-α therapy improved the metabolic and inflammatory profile and modulated IL-6, CDCP-1 and PON-3 levels, supporting its role in managing CV risks in axSpA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>WNK2</i> variants associated with familial osteoarthritis alter the chondrocyte response to hyperosmotic stress.","authors":"Shivakumar R Veerabhadraiah, Derek J Matheson, Matthew Honeggar, Collin Aslor, Antonio C Zelada, Chris Stubben, Gregory J Stoddard, Nikolas H Kazmers, David J Grunwald, Michael J Jurynec","doi":"10.1136/rmdopen-2025-005707","DOIUrl":"10.1136/rmdopen-2025-005707","url":null,"abstract":"<p><strong>Objective: </strong>Chondrocytes of the synovial joint sense and respond to changes in osmolarity to maintain joint homeostasis. We hypothesised that an abnormal response to osmotic stress is a contributing factor to loss of joint homeostasis and the development of osteoarthritis (OA). Our goal was to identify whether genetic variants affecting the response to osmotic stress were associated with susceptibility to OA.</p><p><strong>Methods: </strong>Genomic analysis of independent families with dominant inheritance of OA revealed novel <i>WNK2</i> coding variants that segregated with occurrence of OA. WNK2 expression was examined by immunohistochemistry on normal and osteoarthritic tissue isolated from humans and mice. Wild type (WT) and variant WNK2 functions were analysed by overexpression effects in immortalised and primary human chondrocytes; loss-of-function effects were analysed in <i>WNK2</i> mutant cells. Transcriptomic analyses were used to identify genes and pathways dependent on WNK2 function and hyperosmotic stress.</p><p><strong>Results: </strong>We identified novel coding variants of <i>WNK2</i> associated with familial erosive hand OA and foot OA. <i>WNK2</i> is expressed in chondrocytes and its expression is highly elevated in end-stage human and mouse OA joints. When challenged by hyperosmotic stress, chondrocytes initiate a remodelling response, altering expression of both anabolic and catabolic genes and pathways. However, the combination of elevated WNK2 expression and hyperosmotic stress promotes a WNK2-dependent OA-associated transcriptional response that is exacerbated by expression of the OA-associated <i>WNK2</i> variants.</p><p><strong>Conclusions: </strong>Our data indicate elevated WNK2 signalling is associated with heightened susceptibility to OA. We hypothesise the synergistic effects of hyperosmotic stress and high WNK2 activity promote the development of OA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144542086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: COVID-19 outcomes in patients with rheumatoid arthritis with biologic or targeted synthetic DMARDs.","authors":"","doi":"10.1136/rmdopen-2023-003038corr1","DOIUrl":"10.1136/rmdopen-2023-003038corr1","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144542087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}