Rheumatology最新文献

{"title":"Shorter reproductive time span and early menopause increase the risk of ACPA-negative inflammatory arthritis in postmenopausal women with clinically suspect arthralgia.","authors":"Judith W Heutz, Anna M P Boeren, Stijn Claassen, Elise van Mulligen, Pascal H P de Jong, Annette H M van der Helm-van Mil","doi":"10.1093/rheumatology/keaf083","DOIUrl":"10.1093/rheumatology/keaf083","url":null,"abstract":"<p><strong>Objectives: </strong>The drop in oestrogen levels during menopause coincides with the peak incidence of rheumatoid arthritis (RA) in women, suggesting a role of oestrogens in its pathophysiology. However, the timing of the effect of oestrogens during RA development is unknown. Studies in the final phase of RA development, from clinically suspect arthralgia (CSA) towards clinically apparent arthritis, are lacking. We hypothesized that shorter lifetime oestrogen exposure might be associated with a higher risk of inflammatory arthritis (IA) development in women with CSA and studied this in two cohorts.</p><p><strong>Methods: </strong>Consecutively included women from two independent CSA cohorts, including a total of 433 patients, were prospectively studied. Time to inflammatory arthritis (IA) and RA development was compared for pre- vs postmenopausal women and, in postmenopausal women, for three measures of lifetime duration of oestrogen exposure: number of reproductive years, number of ovulatory years and early menopause. Analyses were stratified for ACPA status.</p><p><strong>Results: </strong>Postmenopausal women, compared with premenopausal women, had an increased risk for ACPA-negative IA (HR 2.9, 95%CI 1.05-8.0) but not for ACPA-positive IA (HR 0.8, 95%CI 0.4-1.9). Results were similar for RA development. Furthermore, early onset of menopause (HR 11.1, 95%CI 2.4-51.1), lower number of reproductive years (HR per 1 year increase 0.88, 95%CI 0.78-0.99), and lower number of ovulatory years (HR per 1 year increase 0.88, 95%CI 0.78-0.99) increased the risk of ACPA-negative IA, but not ACPA-positive IA.</p><p><strong>Conclusion: </strong>In patients with arthralgia at risk for RA, lifetime exposure to oestrogens and/or the drop in oestrogen levels after menopause might play a role in the pathophysiology of ACPA-negative RA.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3451-3457"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415082","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":"Elevated Fcy receptor expression augments pro-inflammatory macrophage phagocytosis in systemic sclerosis and associated rheumatic diseases.","authors":"Amela Hukara, Gino A Bonazza, Tracy Tabib, Raphael Micheroli, Suzana Jordan, Kristina Bürki, Michal Rudnik, Adrian Ciurea, Oliver Distler, Robert Lafyatis, Przemysław Błyszczuk, Gabriela Kania","doi":"10.1093/rheumatology/keae688","DOIUrl":"10.1093/rheumatology/keae688","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the pro-phagocytic phenotype of macrophages in SSc and other rheumatic diseases by examining their activation, signalling pathways and treatment responses, with the goal of uncovering mechanisms that drive enhanced phagocytosis.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) datasets (GSE138669/GSE212109) from skin and lung macrophages of healthy controls (HC) and SSc patients were analysed. Human monocyte-derived macrophages (hMDMs) were differentiated from CD14+ monocytes from HC, SSc, RA, PsA, and axSpA patients. In selected experiments, hMDMs were pretreated with 0.1 μM nintedanib. Phagocytic activity was quantified using pHrodo bioparticles and flow cytometry. Macrophage surface markers were evaluated by flow cytometry, NF-κB signalling by Western blot and gene expression by RT-qPCR.</p><p><strong>Results: </strong>Analysis of scRNA-seq datasets revealed a pro-phagocytic signature in SSc-affected organs. SSc macrophages, particularly the FCGR3Ahi cluster in skin, exhibited elevated expression of FCGR genes and enriched FcγR-mediated phagocytosis pathways, accompanied by pro-inflammatory markers. This phenotype extended to FCN1hi lung macrophages in SSc patients with interstitial lung disease, indicating a systemic pro-inflammatory and phagocytic profile. hMDMs from SSc, RA and PsA patients demonstrated enhanced phagocytic activity in vitro. Elevated FcγRI and FcγRII levels were identified as key drivers of increased phagocytic activity and subsequent IL-6-driven inflammation. Nintedanib showed reduction in FcγRI expression, suggesting its potential therapeutic benefit in attenuating the phagocytic process.</p><p><strong>Conclusion: </strong>This study highlights FcγR-expressing macrophages as drivers of phagocytosis and inflammatory responses in SSc. Dysregulated activation of these macrophages could lead to persistent inflammation and fibrosis in rheumatic diseases, highlighting new potential therapeutic approaches.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3975-3988"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822560","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":"Anti-Sp4 and anti-CCAR1 autoantibodies in UK vs US patients with adult and juvenile-onset anti-TIF1γ-positive myositis.","authors":"Fionnuala K McMorrow, Lucy R Wedderburn, Hector Chinoy, Alexander Oldroyd, Janine A Lamb, Lisa G Rider, Andrew L Mammen, Livia Casciola-Rosen, Neil J McHugh, Sarah L Tansley","doi":"10.1093/rheumatology/keae574","DOIUrl":"10.1093/rheumatology/keae574","url":null,"abstract":"<p><strong>Objectives: </strong>Anti-transcriptional intermediary factor 1γ (TIF1γ) autoantibodies are associated with malignancy in adult-onset idiopathic inflammatory myopathy (IIM) and this risk is attenuated if patients are also positive for anti-specificity protein 4 (Sp4) or anti-cell division cycle apoptosis regulator protein 1 (CCAR1). In anti-TIF1γ positive dermatomyositis (DM) patients from the USA, anti-Sp4 and anti-CCAR1 autoantibody frequencies are reported as 32% and 43% in adults and 9% and 19% in juveniles, respectively. This study aims to identify the frequency of anti-Sp4 and anti-CCAR1 in adult and juvenile UK anti-TIF1γ-positive myositis populations and report clinical associations.</p><p><strong>Methods: </strong>Serum samples from 51 UK participants with adult-onset IIM and 55 UK participants with JDM, all anti-TIF1γ autoantibody positive, and 24 healthy control samples were screened for anti-Sp4 and anti-CCAR1 autoantibodies by ELISA.</p><p><strong>Results: </strong>In UK adult anti-TIF1γ positive IIM patients, anti-Sp4 and anti-CCAR1 frequencies were 4% (2/51) and 16% (8/51). Both adult patients with anti-Sp4 were also positive for anti-CCAR1. In UK juveniles, anti-Sp4 was not detected and 13% (7/55) had anti-CCAR1 autoantibodies. Nineteen (37%) anti-TIF1γ positive UK adult myositis patients had cancer; neither of the two patients with anti-Sp4 autoantibodies and 25% (2/8) of anti-CCAR1 autoantibody-positive patients had cancer. No anti-Sp4 or anti-CCAR1 clinical associations were identified.</p><p><strong>Conclusion: </strong>Anti-Sp4 and anti-CCAR1 autoantibodies are less common in the adult UK anti-TIF1γ-positive myositis population compared with published data from the USA, limiting their use as biomarkers for cancer risk. In patients with juvenile onset disease, anti-Sp4 is less frequent in UK patients compared with the USA, but the prevalence of anti-CCAR1 autoantibodies is similar.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3900-3905"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605798","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":"Can treatment expectations or treatment itself in patients with arthralgia suspicious for progression to rheumatoid arthritis improve illness perceptions?","authors":"Simonetta R G van Griethuysen, Quirine A Dumoulin, Elise van Mulligen, Annette H M van der Helm-van Mil","doi":"10.1093/rheumatology/keaf095","DOIUrl":"10.1093/rheumatology/keaf095","url":null,"abstract":"<p><strong>Objectives: </strong>Negative illness perceptions (IPs) are associated with poorer disease outcomes in rheumatoid arthritis (RA). Unfortunately, IPs are generally stable in established RA. We hypothesized that IPs, especially in the cognitive domain, are modifiable in arthralgia at risk of RA. We aimed to study if receiving DMARD treatment, or the offer of DMARD treatment associates with more positive IPs in patients with clinically suspect arthralgia (CSA).</p><p><strong>Methods: </strong>The population studied were CSA patients to which a wait-and-see approach was adopted without offering DMARD treatment, or patients were offered DMARD treatment via the TREAT EARLIER trial and subsequently randomized to receive methotrexate or placebo. IPs were assessed using the Brief Illness Perception Questionnaire (BIPQ), covering cognitive, emotional and comprehensibility domains. The effect of DMARD treatment on IPs over time was studied by comparing the 2-year course of BIPQs of patients receiving methotrexate or placebo. The effect of offering DMARD treatment was examined by comparing the BIPQs of CSA patients in the trial with those undergoing a wait-and-see policy.</p><p><strong>Results: </strong>In total, 375 CSA patients were studied, of which 236 of the TREAT EARLIER trial and 139 with a wait-and-see approach. Patients who received treatment showed sustained improvements in IPs over time compared with placebo in four cognitive domains: experience of physical complaints (P = 0.040), the illness's influence on life (P = 0.001), treatment effectiveness (P = 0.041) and disease duration (P = 0.045). Comparison at baseline showed that CSA patients to whom treatment was offered had more confidence in treatment (P < 0.001) and tended to have a deeper understanding of their disease (P = 0.054).</p><p><strong>Conclusion: </strong>Both the prospect of and DMARD treatment itself improved IPs in CSA, mainly in cognitive domains. These data suggest CSA as a suitable time period for influencing IPs, which may provide possibilities to improve disease outcomes in patients developing RA.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3444-3450"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410403","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":"Association of patient- and hospital-level predictors with patterns of initial treatment in patients with rheumatoid arthritis: findings from a national cohort study.","authors":"Zijing Yang, Edward Alveyn, Mark Russell, Katie Bechman, Callum Coalwood, Elizabeth Price, Abhishek Abhishek, Sam Norton, James Galloway","doi":"10.1093/rheumatology/keae717","DOIUrl":"10.1093/rheumatology/keae717","url":null,"abstract":"<p><strong>Objectives: </strong>To update the first-line conventional synthetic DMARDs (csDMARDs) prescribing pattern, describe change and variation across demographical and geographical factors in the RA population, and identify individual and hospital factors associated with it.</p><p><strong>Methods: </strong>This retrospective cohort study included newly diagnosed RA adult patients from 1 May 2018 to 1 April 2023 in the UK. We used adjusted multinomial logistic regression with random effect to explore associations with different first-line csDMRAD prescription and to account for hospital-level clustering.</p><p><strong>Results: </strong>We identified 15 462 RA patients who received csDMARD treatment. Overall, 57% received MTX monotherapy and 14% received MTX combination therapy as first-line treatment. MTX is the most frequently medication, following by HCQ and SSZ. Compared with non-MTX prescription, prescription of MTX monotherapy [adjusted odds ratio (aOR) 1.25 95% CI (1.22-1.29)] and MTX combination therapy [aOR 1.45 (1.38-1.52)] was significantly higher in patients with higher DAS28, but lower in the non-White individuals with comorbidities: lung disease, cancer, fracture and heart attack. Among those who received MTX, monotherapy is more likely be prescribed in patients with higher DAS28 [aOR 1.08 (1.05-1.11)] and without lung disease [aOR 0.5 (0.44-0.56)], compared with combination therapy. Around 20% of the variability in first-line csDMARD prescribing was attributed to the hospital level.</p><p><strong>Conclusion: </strong>In this cohort study of new-onset RA population, both individual- and institution-level variation in first-line csDMARD treatment strategy was evident. Gender, ethnicity, disease activity, and comorbidities, especially lung disease, were associated with disparities at the individual level.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3379-3387"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882870","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":"The impact of an online, lifestyle intervention programme on the lives of patients with a rheumatic and musculoskeletal disease: a pilot study.","authors":"Kim van Slingerland, Laura J C Kranenburg, Nathalie Wilmsen, Emma Coles, Radboud J E M Dolhain, Pascal H P de Jong","doi":"10.1093/rheumatology/keae696","DOIUrl":"10.1093/rheumatology/keae696","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the short- and long-term effects of an online, interactive, multifactorial lifestyle intervention programme (Leef! Met Reuma) on health risk and all ICHOM-recommended patient-reported outcome measures (PROMs) in patients with an inflammatory arthritis (IA), osteoarthritis (OA) or fibromyalgia (FM).</p><p><strong>Methods: </strong>Patients with an IA, OA or FM could register for the lifestyle intervention programme. The programme consists of a 3-month intensive part followed by a 21-month aftercare period and focuses on four pillars, namely nutrition, exercise, relaxation and sleep. Health risk and PROMs are collected 3-monthly during the first 6 months and 6-monthly during the next 18 months. Health risk includes self-reported weight, waist circumference and BMI. Following PROMs were included: pain, morning stiffness severity, fatigue, Health Assessment Questionnaire, quality of life, perceived stress, sleep disturbance and impact on life. Descriptive statistics were used to assess the change in health risk and PROMs during the intensive part of the programme and aftercare period.</p><p><strong>Results: </strong>Of the 264 patients studied, 88, 105 and 71 were diagnosed with IA, OA and FM, respectively. Health risk significantly improved in all three diagnosis groups during the intensive part of the programme. The mean BMI reduction was -1.36 (0.26), -1.22 (0.23) and -1.48 (0.33), whereafter it stabilized in the aftercare period. All PROMs showed a similar trend.</p><p><strong>Conclusion: </strong>An online, interactive lifestyle intervention programme has a positive long-term effect, even after 2 years of follow-up, on health risk and all PRO domains in patients with an IA, OA and FM.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3309-3318"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882851","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":"A phase 2 randomized trial of safety and pharmacokinetics of IgPro20 and IgPro10 in patients with diffuse cutaneous systemic sclerosis.","authors":"Christopher P Denton, Otylia Kowal-Bielecka, Susanna M Proudman, Marzena Olesińska, Margitta Worm, Nicoletta Del Papa, Marco Matucci-Cerinic, Jana Radewonuk, Jeanine Jochems, Adrian Panaite, Amgad Shebl, Anna Krupa, Yannick Allanore, Jutta H Hofmann, Maria J Gasior","doi":"10.1093/rheumatology/keaf066","DOIUrl":"10.1093/rheumatology/keaf066","url":null,"abstract":"<p><strong>Objectives: </strong>The primary objective was the safety of s.c. immunoglobulin, IgPro20 (Hizentra, CSL Behring) in adults with dcSSc. Secondary objectives included pharmacokinetics and relative bioavailability of IgPro20, and safety and pharmacokinetics of IVIG, IgPro10 (Privigen, CSL Behring).</p><p><strong>Methods: </strong>In this prospective, multicentre, randomized, open-label, crossover phase 2 study (NCT04137224), patients (aged ≥18 years) with dcSSc were assigned to 16 weeks of IgPro20 (0.5 g/kg/week) followed by 16 weeks of IgPro10 (2 g/kg/4 weeks over two to five sessions), or vice versa. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infusion site reactions (ISRs), clinical tests, pharmacokinetic and bioavailability were assessed.</p><p><strong>Results: </strong>Twenty-seven patients were randomized from 9 October 2019 to 31 August 2021. In total, 22 patients (81.5%) experienced 107 TEAEs (IgPro20, 49; IgPro10, 58); most were mild/moderate. Six patients (22.2%) experienced 10 SAEs (IgPro20, 6; IgPro10, 4); no treatment-related SAEs and no deaths were reported. IgPro20 ISR rate was low (2 per 100 infusions). Maximum IgG concentration [mean (s.d.)] was numerically lower following IgPro20 [23.7 (1.2) g/l] vs IgPro10 [46.1 (1.2) g/l], as was the geometric mean dose-normalized, baseline-corrected area under the concentration-time curve from time point 0 to tau [IgPro20, 44.8 (1.4) h*g/l; IgPro10, 60.2 (1.4) h*g/l]. The bioavailability of IgPro20 relative to IgPro10 was 76.1%.</p><p><strong>Conclusion: </strong>This study shows that in patients with dcSSc, safety, pharmacokinetic and bioavailability profiles of IgPro20, and safety and pharmacokinetics of IgPro10, are similar to those observed in other approved indications.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, https://clinicaltrials.gov, NCT04137224.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3657-3666"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255967","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":"Long-term follow-up after discontinuation of anti-IL1 treatment in colchicine-resistant familial Mediterranean fever.","authors":"Veysel Cam, Yagmur Bayindir, Yelda Bilginer, Seza Ozen","doi":"10.1093/rheumatology/keaf154","DOIUrl":"10.1093/rheumatology/keaf154","url":null,"abstract":"","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"4064"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658494","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":"Cell-integrated serum-induced signalling patterns can differentiate between hand and knee osteoarthritis patients.","authors":"Margot Neefjes, Bas A C Housmans, Charlotte Kaffa, Nathalie G M Thielen, Leo A B Joosten, Cornelia H M van den Ende, Elly L Vitters, Guus G H van den Akker, Tim J M Welting, Arjan P M van Caam, Peter M van der Kraan","doi":"10.1093/rheumatology/keae555","DOIUrl":"10.1093/rheumatology/keae555","url":null,"abstract":"<p><strong>Objective: </strong>OA is a very heterogeneous disease. Here, we aimed to differentiate OA patients based on their serum-induced cell-integrated signalling patterns.</p><p><strong>Design: </strong>In order to monitor the activity of different cellular homeostasis-regulating pathways in response to patient serum, we analysed the response of human OA serum samples to 16 cell-based transcription factor luciferase reporter assays. In this study we compared serum samples from 55 patients with knee OA, 56 patients with hand OA and 42 healthy controls.</p><p><strong>Results: </strong>Differential serum-induced pathway activity was observed between samples from healthy controls, knee OA and hand OA patients: serum of hand OA patients induced high MAPK-related AP1 activity whereas serum of knee OA patients induced more SRE, ISRE and SOX9 activity, which is related to ELK1-SRF, STAT1-STAT2 and SOX9 activity, respectively. Principal component analysis revealed that these differences differentiate hand OA from knee OA. Both hand and knee OA clustered clearly in two different endotypes each, but no principle component could be identified of these subtypes within either the hand OA or the knee OA sample group.</p><p><strong>Conclusion: </strong>This study demonstrates that serum from hand OA and knee OA patients evokes diverse cellular signalling patterns that differentiates hand OA, knee OA and healthy controls. This underlines that the pathomolecular mechanisms of OA are likely significantly different between hand and knee OA, a finding that could lead to new insight into the pathobiology of OA endotypes and joint-specific therapies.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3929-3937"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668953","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":"Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry.","authors":"Yohei Kirino, Ayaka Maeda, Tomoyuki Asano, Kiyoshi Migita, Yukiko Hidaka, Hiroaki Ida, Daisuke Kobayashi, Nobuhiro Oda, Ryo Rokutanda, Yuichiro Fujieda, Tatsuya Atsumi, Dai Kishida, Hiroshi Kobayashi, Motoaki Shiratsuchi, Toshimasa Shimizu, Atsushi Kawakami, Kazuki Tanaka, Tomohiro Tsuji, Koji Mishima, Takako Miyamae, Anna Hasegawa, Kei Ikeda, Tomoya Watanabe, Yukie Yamaguchi, Ryuta Nishikomori, Osamu Ohara, Hideaki Nakajima","doi":"10.1093/rheumatology/keae530","DOIUrl":"10.1093/rheumatology/keae530","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study.</p><p><strong>Methods: </strong>Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure VEXASCAF assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels and treatments were also recorded at enrolment and 3 months after enrolment. All exons of ubiquitin-like modifier activating enzyme 1 (UBA1) were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients.</p><p><strong>Results: </strong>Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including three deaths, four malignancies from two cases, two thromboses and 13 infections (including four mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling and pain) were the most common AEs.</p><p><strong>Conclusions: </strong>Patients with VEXAS syndrome required high-dose glucocorticoids to reduce disease activity, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3872-3878"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}