RMD Open最新文献

{"title":"Burden of coronary artery calcification in ANCA-associated vasculitis.","authors":"Michael Hendrickson, Anushri Parakh, Brittany Weber, Claire Cook, Catherine Ahola, Sandeep Hedgire, Michael Lu, Zachary S Wallace","doi":"10.1136/rmdopen-2024-004774","DOIUrl":"10.1136/rmdopen-2024-004774","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) is a leading cause of death in ANCA-associated vasculitis (AAV). Screening and primary cardiovascular prevention may improve outcomes.</p><p><strong>Methods: </strong>We identified patients in the 2002-2019 Mass General Brigham AAV cohort with thoracic CT scans obtained for other clinical purposes. Coronary artery calcium (CAC) scores and age, sex and race-standardised CAC percentiles were calculated. Quantile regression was used to identify differences by ANCA type, and Gray's test examined differences in major adverse cardiac events by CAC score.</p><p><strong>Results: </strong>Of 175 included patients, 127 (73%) were MPO-ANCA+and 48 (27%) were PR3-ANCA+. The median CAC score was 17 (IQR 0, 334) and CAC percentile was 45 (IQR 0, 78); 65 (39%) patients had CAC of ≥100. The total CAC score was higher in patients with MPO-ANCA+AAV vs PR3-ANCA+AAV (median 24 vs 1, p=0.003), as was the standardised CAC percentile (50th vs 34th, p=0.02). Of 116 (66%) patients with non-zero CAC scores, only 29 (25%) were on a statin. In a time-to-event analysis, CAC of 100 or higher trended towards association with higher risk of major adverse cardiovascular events (χ²=1.9, p=0.16).</p><p><strong>Conclusion: </strong>A majority of patients with AAV had clinically significant CAC. There were differences in CAC burden among those with MPO-ANCA+AAV versus PR3-ANCA+AAV. Although CAC is associated with CVD risk and an indication for statins, the use was inconsistent. The role of CT imaging to screen for CVD and guide primary prevention in AAV requires further study.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010885","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":"Evaluation of rheumatoid arthritis-associated interstitial lung disease in patients treated with JAK inhibitors: a MAJIK-SFR cohort study.","authors":"Félicien Triboulet, Pierre-Antoine Juge, Marie-Elise Truchetet, Thao Pham, Nicolas Roux, René-Marc Flipo, Charles Leské, Christian Hubert Roux, Raphaele Seror, André Basch, Olivier Brocq, Pascal Chazerain, Fabienne Coury-Lucas, Richard Damade, Emanuelle Dernis, Jacques-Eric Gottenberg, André Ramon, Adeline Ruyssen-Witrand, Jean Hugues Salmon, Émilie Shipley, Anne Tournadre, Clement Prati, Philippe Dieudé, Jerome Avouac","doi":"10.1136/rmdopen-2024-005062","DOIUrl":"10.1136/rmdopen-2024-005062","url":null,"abstract":"<p><strong>Objective: </strong>To examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.</p><p><strong>Methods: </strong>Prospective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers.</p><p><strong>Results: </strong>We enrolled 42 patients (26 women, 62%) with RA-ILD with a mean age of 61±13 years and a mean disease duration of 16±10 years. Compared with the 778 RA patients without ILD from the MAJIK registry, RA-ILD patients were older, displayed more severe and active disease and had more prevalent comorbidities. Non-specific interstitial pneumonia and usual interstitial pneumonia accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. No significant changes in FVC and DLCO were observed during the follow-up period. Chest HRCT lesions remained stable in 69% of patients. Progressive ILD was identified in 8 patients (19%). 16 (38%) respiratory tract infections were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed. No deaths occurred. JAKi was discontinued in 17 patients including 8 for inefficacy on joint involvement and 5 for intolerance.</p><p><strong>Conclusion: </strong>The analysis indicates stability of RA-ILD in patients treated with JAKi. The tolerance profile of JAKi in this higher risk population did not reveal new safety signal.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010911","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 between resolution of MRI-detected inflammation and improved clinical outcomes in axial spondyloarthritis under long-term anti-TNF therapy.","authors":"Murat Torgutalp, Judith Rademacher, Fabian Proft, Kay-Geert Hermann, Christian Althoff, H Haibel, Mikhail Protopopov, Joachim Sieper, Valeria Rios Rodriguez, Denis Poddubnyy","doi":"10.1136/rmdopen-2024-004921","DOIUrl":"10.1136/rmdopen-2024-004921","url":null,"abstract":"<p><strong>Objectives: </strong>In this post-hoc analysis of ESTHER trial, we aimed to investigate the longitudinal relationship between inflammation on MRI and the achievement of inactive disease/low disease activity in patients with axial spondyloarthritis (axSpA) treated with long-term tumor necrosis factor (TNF) inhibitor etanercept.</p><p><strong>Methods: </strong>Of the 76 patients with active axSpA in the ESTHER trial, we included all patients treated with etanercept for at least 6 months for main analysis. All clinical and MRI data from 4.5 years of follow-up were used in the analysis. MRIs of the spine and sacroiliac (SI) joints were performed at baseline, week 24, week 48 and yearly thereafter and were evaluated for active inflammatory lesions according to the Berlin MRI score.</p><p><strong>Results: </strong>Longitudinal analysis showed that higher SI joint osteitis score was associated with higher Axial Spondyloarthritis Disease Activity Score (ASDAS) at the same time point (β=0.08, 95% CI (0.05; 0.11)) and at the next time point 6 months later (β=0.05, 95% CI (0.02; 0.07)). Furthermore, resolution of osteitis in the SI joint (Berlin MRI osteitis score of ≤1) was associated with lower ASDAS at the next time point (β=-0.26, 95% CI (-0.42; -0.09)), higher odds of achieving ASDAS low disease activity (OR=5.61, 95% CI (1.06; 29.67)) and inactive disease status (OR=2.23, 95% CI (1.01; 4.94)) at the next time point.</p><p><strong>Conclusions: </strong>The presence of inflammation on SI joints-MRI is associated with higher disease activity in axSpA. Resolution of inflammation on MRI is associated with better clinical outcomes in the long-term follow-up. Thus, achieving complete resolution of inflammation is favourable for meeting the treatment goals in axSpA.</p><p><strong>Trial registration number: </strong>NCT00844142.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010871","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":"Reference intervals of work ability and productivity loss and their use in patients with inflammatory rheumatic and musculoskeletal diseases.","authors":"Dafne Capelusnik, Wouter Smeets, Casper Webers, Sofia Ramiro, Elena Nikiphorou, Roel Braekers, Laura Boekel, Gertjan Wolbink, Annelies Boonen","doi":"10.1136/rmdopen-2024-004877","DOIUrl":"10.1136/rmdopen-2024-004877","url":null,"abstract":"<p><strong>Objectives: </strong>To establish reference intervals (RIs) for work ability, at-work productivity loss and overall productivity loss in the general working population and to compare work ability and at-work productivity loss of patients with inflammatory rheumatic and musculoskeletal disease (iRMD) with this population.</p><p><strong>Methods: </strong>Cross-sectional analysis among patients with iRMDs and population controls without iRMDs having paid work and participating in a Dutch cohort study. They reported on three work outcomes: work ability (0-10), at-work productivity loss and overall productivity loss (0%-100%). A generalised additive model for location, shape and scale parameters was used to establish age-specific RIs and percentile curves for controls. The proportion of patients and controls below each percentile curve was compared.</p><p><strong>Results: </strong>413 controls were included; 73% female, with mean age 53 (SD 10) years, 60% had high education, mean work ability was 8.7 (1.6), at-work productivity loss 6.3% (7.2) and overall work productivity loss 11% (25.6).Percentile curves illustrated that work ability and at-work/overall work productivity loss were worse with increasing age. For instance, for work ability, the 95% RI for 22 to 29-year individuals was 5.9-10, while for individuals between 50 and 59 years, it was 4.9-9.1. Patients compared with controls had worse work outcomes, especially for at-work and overall productivity loss.</p><p><strong>Conclusion: </strong>Work ability and productivity are not perfect in the general population, based on the newly developed RIs for the three work outcomes. This calls for caution to not overestimate the iRMD impact on work outcomes. Nevertheless, iRMD patients have worse work ability and higher work productivity loss, compared with controls.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010991","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":"Efficacy of valaciclovir in preventing herpes zoster in patients receiving anifrolumab.","authors":"Ludovic Trefond, Francois Chasset, Marie Jachiet, Cristina Livideanu, Thomas Barba, Stanislas Faguer, Julien Henry, Gaelle Richard-Colmant, Nicole Ferreira-Maldent, Sandrine Roque, Ruben Monteiro, Kevin Chevalier, Aurelia Lanteri, Estibaliz Lazaro, Marc Scherlinger, Nicolas Belhomme, Christophe Richez, Claire Cazalets, Laurent Sailler, Nassim Ait Abdallah, Jeanne de La Rochefoucauld, Julien Campagne, Alexandra Audemard, Thomas Moulinet, Noemie Abisror, Nathalie Costedoat-Chalumeau, Cecile Lesort, Didier Bessis, Diane Kottler, Cecile Saint-Pastou Terrier, Pierre-Yves Jeandel, Sarah Lechtman, Chloé Grolleau, Jérome Hadjadj, Bruno Pereira, Perrine Smets, Marc André, Jean-David Bouaziz, Alexis Mathian, Zahir Amoura","doi":"10.1136/rmdopen-2024-005076","DOIUrl":"10.1136/rmdopen-2024-005076","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932648","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":"Reliability of the OMERACT Giant cell arteritis Ultrasonography Score (OGUS): results of a patient-based exercise involving experts and non-experts in vascular ultrasonography.","authors":"Christina Duftner, Norbert Redlinger, George A Bruyn, Veerendra Chadachan, Stavros Chrysidis, Maria Correyero, Maria Antonietta D'Agostino, Berit Dalsgaard Nielsen, Bhaskar Dasgupta, Eugenio De Miguel, Andreas P Diamantopoulos, Giovanni Fulvio, Nikitas Gkikopoulos, Wolfgang Hartung, Alojzija Hocevar, Helen Keen, Vesselina Kurteva, Peter Mandl, Eva Manger, Paolo Mercatelli, Irina Midtgard, Sara Monti, Raili Muller, Kati Mykkänen, Carlos Pineda, Cristina Ponte, Duriad Reffat, Adela-Cristina Sarbu, Luca Seitz, Lene Terslev, Wolfgang A Schmidt, Christian Dejaco","doi":"10.1136/rmdopen-2024-004667","DOIUrl":"10.1136/rmdopen-2024-004667","url":null,"abstract":"<p><strong>Objective: </strong>To test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography.</p><p><strong>Methods: </strong>Six GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2. Ultrasonography was conducted on temporal arteries (common superficial, frontal and parietal branches) and axillary arteries bilaterally to calculate the OGUS, the Southend score and the Halo count. Inter-reader and intra-reader reliability were assessed by intraclass correlation coefficient (ICC).</p><p><strong>Results: </strong>Mean age of GCA patients was 78±5.1 years, 2 (33.3%) were women, and all were in clinical remission. Expert inter-reader ICC of the OGUS was 0.60 in both rounds, 0.40 in round 1 and 0.51 in round 2 for the Southend score and 0.45 and 0.52, respectively, for the Halo count. Median ICCs for intra-reader reliability were 0.86, 0.73 and 0.65 for the OGUS, Southend score and Halo count, respectively.For non-experts, inter-reader ICCs in round 1 were 0.20 for the OGUS, 0.20 for a normalised Southend score (=score divided by available segments) and 0.35 for a normalised Halo count. After training, inter-reader reliability ICCs improved to 0.52, 0.29 and 0.54, respectively.</p><p><strong>Conclusion: </strong>Inter-reader reliability was fair to moderate, and intra-reader reliability was good for OGUS, Southend score and Halo count among experts. Inter-reader reliability of non-experts in vascular ultrasonography improved after the training.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927330","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":"Efficacy and safety of jaktinib hydrochloride tablets in active axial spondyloarthritis: a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial.","authors":"Juan Wang, Chunde Bao, Qing Dai, Antao Xu, Yan Ye","doi":"10.1136/rmdopen-2024-004865","DOIUrl":"10.1136/rmdopen-2024-004865","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to evaluate the efficacy and safety of jaktinib hydrochloride tablets (jaktinib), a Janus kinase inhibitor, in patients with active radiographic axial spondyloarthritis (r-axSpA).</p><p><strong>Methods: </strong>Adults with active r-axSpA who met modified New York criteria and had an inadequate response to non-steroidal anti-inflammatory drugs were randomised 1:1:1 to receive jaktinib 75 mg two times per day, 100 mg two times per day, or placebo. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society 20 (ASAS 20) and ASAS 40 responses, respectively, at week 16. Safety was evaluated by analysing adverse events.</p><p><strong>Results: </strong>A total of 107 patients with active r-axSpA were randomised (jaktinib 75 mg two times per day, n=35; jaktinib 100 mg two times per day, n=36; placebo, n=36). In the ASAS20 response rates, the 100 mg two times per day group had the highest response at 61.1%, followed by the 75 mg two times per day group at 57.1%, and the placebo group had the lowest at 33.3% for the 16 weeks of treatment. The ASAS40 response rates were significantly higher with jaktinib (100 mg two times per day group: 47.2%, 75 mg two times per day group: 37.1%) compared with placebo (13.9%). The incidence of treatment-emergent adverse events in the 75 mg two times per day, 100 mg two times per day and placebo groups was 88.6% versus 94.4% versus 86.1%, respectively, with no statistically significant difference among the three groups. No major adverse cardiovascular events, malignancy, thromboembolism or deaths were reported.</p><p><strong>Conclusions: </strong>Jaktinib showed good efficacy and tolerability in the treatment of active r-axSpA, with the 100 mg two times per day showing a trend towards better efficacy.</p><p><strong>Trial registration number: </strong>NCT04507659.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927160","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":"Body composition is associated with changes in health-related quality of life in patients with knee and/or hip osteoarthritis.","authors":"Anne-Christine Rat, Jérémie Sellam, Bernard Mazières, Willy Ngueyon Sime, Patrice Fardellone, Francis Guillemin","doi":"10.1136/rmdopen-2024-004733","DOIUrl":"10.1136/rmdopen-2024-004733","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to analyse the association between body composition and changes in health-related quality of life (HRQoL) of patients followed for hip and knee osteoarthritis (OA).</p><p><strong>Methods: </strong>Longitudinal data from the Knee and Hip OsteoArthritis Long-term Assessments (KHOALA) cohort, a multicentre cohort of 878 patients with symptomatic knee and/or hip OA, were used. The main outcome criteria were changes in patient-reported outcomes measures, the Study Short Form-36 (physical functioning, pain, mental health and vitality) and the OsteoArthritis Knee and Hip Quality Of Life (OAKHQOL)(physical activity, pain and mental health). Body composition measurements were obtained from dual X-ray absorptiometry (DXA) scans in a subsample of 381 patients at year 3. Body composition variables were fat mass index (FMI (kg/m²)), percentage of fat mass, trunk to leg fat mass ratio (TFM/LFM) and skeletal muscle mass index (SMI (kg/m²)). To account for the correlation of repeated measures in each individual, GEE models were used.</p><p><strong>Results: </strong>290 patients with knee and 114 patients with hip OA were included in the analysis. In multivariate analysis, higher FMI at baseline and the presence of low lean mass were independently associated with worse physical functioning over time (β -0.02, 95% CI -0.03 to -0.01, p<0.0001 and β -0.21, 95% CI -0.02 to 0.02, p=0.02) for SF-36 dimensions. Higher TFM/LFM and SMI at baseline were associated with better mental health (β 0.09, 95% CI 0.02 to 0.15, p=0.008 and β 0.01, 95% CI 0.006 to 0.02, p<0.0001) and vitality. No association between body composition measures and pain remained in the multivariate analysis.</p><p><strong>Conclusions: </strong>Higher FMI at baseline and the presence of low muscle mass were independently associated with worse physical function over 4 years, but not with pain. Higher TFM/LFM and SMI at baseline were associated with better mental health and vitality over time.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927068","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":"Fine-tuning SLE treatment: the potential of selective TYK2 inhibition.","authors":"Yurie Satoh-Kanda, Shingo Nakayamada, Yoshiya Tanaka","doi":"10.1136/rmdopen-2024-005072","DOIUrl":"10.1136/rmdopen-2024-005072","url":null,"abstract":"<p><p>In systemic lupus erythematosus (SLE), adaptive immunity is activated by the stimulation of innate immunity, leading to the development of autoreactive T cells and activation and differentiation of B cells. Cytokine signalling plays an essential role in the pathogenesis and progression of this disease. In particular, the differentiation and function of CD4+ T cell subsets, which play a central role in SLE pathology, are significantly altered by cytokine stimulation. Many cytokines transmit signals via the Janus-activated kinase (JAK)-STAT pathway, but there is no one-to-one correspondence between cytokine receptors and JAK/TYK2. Multiple cytokines activate JAK/TYK2, and multiple JAK/TYK2 molecules are simultaneously activated by a single cytokine. Therefore, the modulation of the JAK-STAT pathway has the potential to control immune responses in SLE. Although several JAK/TYK2 inhibitors are currently undergoing clinical trials, more selective drugs that can target cytokine signals according to the specific pathology of the disease are required. TYK2 inhibitors, which are involved in the signal transduction of type I interferon and interleukin-12/23 pathways and are linked to disease susceptibility genes in SLE, may have the potential to fine-tune the differentiation and function of immune cells, particularly CD4+ T cells.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910437","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":"Induction of interleukin 21 receptor expression via enhanced intracellular metabolism in B cells and its relevance to the disease activity in systemic lupus erythematosus.","authors":"Masanobu Ueno, Shigeru Iwata, Kaoru Yamagata, Yasuyuki Todoroki, Koshiro Sonomoto, Atsushi Nagayasu, Ippei Miyagawa, Satoshi Kubo, Yusuke Miyazaki, Hiroko Miyata, Ryuichiro Kanda, Takafumi Aritomi, Shingo Nakayamada, Yoshiya Tanaka","doi":"10.1136/rmdopen-2024-004567","DOIUrl":"10.1136/rmdopen-2024-004567","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the association between the changes in intracellular metabolism in the early stage of B cell activation and systemic lupus erythematosus (SLE) pathogenesis.</p><p><strong>Methods: </strong>CD19⁺ or CD19⁺CD27^- (naïve) cells from the peripheral blood of healthy controls and lupus patients were cultured under different stimuli. The changes in intracellular metabolism and signalling pathways in these cells were evaluated.</p><p><strong>Results: </strong>Stimulation with CpG (Toll-like receptor 9 (TLR9) ligand) in vitro induced enhanced interleukin 21 (IL-21) receptor expression in CD19⁺CD27^- cells after 24 hours. The addition of IL-21 to the CpG stimulation enhanced the extracellular acidification rate, which indicates glycolysis, within 30 min. IL-21 receptor (IL-21R) expression induced by CpG stimulation was selectively inhibited by 2-deoxy-D-glucose (hexokinase 2 (HK2) inhibitor) and heptelidic acid (glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibitor). RNA immunoprecipitation with anti-GAPDH antibody revealed that CpG stimulation dissociated the binding between IL-21R messenger RNA (mRNA) and GAPDH under no stimulation. HK2 and GAPDH expression were higher in CD19⁺CD27^- cells of lupus patients than in those of healthy controls, and GAPDH expression was correlated with the plasmocyte count and disease activity score.</p><p><strong>Conclusion: </strong>IL-21R mRNA-GAPDH binding dissociation associated with rapid glycolytic enhancement by the TLR9 ligand in B cells may induce plasmocyte differentiation through IL-21 signals and be involved in exacerbating SLE.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"10 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910439","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}