Seminars in arthritis and rheumatism最新文献

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Antigen-specific immunotherapy of multiple sclerosis and other autoimmune diseases.
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152682
David C Wraith
{"title":"Antigen-specific immunotherapy of multiple sclerosis and other autoimmune diseases.","authors":"David C Wraith","doi":"10.1016/j.semarthrit.2025.152682","DOIUrl":"https://doi.org/10.1016/j.semarthrit.2025.152682","url":null,"abstract":"<p><p>Current therapies for autoimmune diseases do not address the underlying cause of disease, the failure of immune tolerance to self. The non-specific therapies currently used to treat autoimmune diseases increase the risk of infections and cancers. Antigen-specific therapies target pathogenic autoreactive lymphocytes while preserving protective immune responses. This short synthesis will review our laboratory's work on the design and development of antigen-specific immunotherapies for multiple sclerosis and other autoimmune diseases.</p>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":" ","pages":"152682"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537695","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}
引用次数: 0
Classification criteria of joint activity using joint index vector for patients with rheumatoid arthritis: An evaluation and verification
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152659
Ichiro Yoshii , Susumu Nishiyama , Naoya Sawada , Tatsumi Chijiwa
{"title":"Classification criteria of joint activity using joint index vector for patients with rheumatoid arthritis: An evaluation and verification","authors":"Ichiro Yoshii ,&nbsp;Susumu Nishiyama ,&nbsp;Naoya Sawada ,&nbsp;Tatsumi Chijiwa","doi":"10.1016/j.semarthrit.2025.152659","DOIUrl":"10.1016/j.semarthrit.2025.152659","url":null,"abstract":"<div><h3>Objectives</h3><div>We developed an activity classification of the joint index vector (JIV) for rheumatoid arthritis (RA) using monitoring data of RA cases at our institute. We verified its validity using an external big dataset (BD).</div></div><div><h3>Methods</h3><div>JIV is a novel joint involvement evaluation method that presents three-axis coordinates. We have set JIV classification criteria to determine a cut-off index (COI) of the combined vector on the x-y axis (Vxy). The z-axis (Vz) in the JIV was determined by Receiver Operating Characteristic analysis (ROC) in referring to the Clinical Disease Activity Index (CDAI) disease activity threshold and Health Assessment Questionnaire Disability Index (HAQ-DI) remission criteria. The criteria of JIV were evaluated in relation to indicators such as the CDAI and HAQ-DI. After determining the criteria, the validity was verified by referring to the simplified disease activity index (SDAI) classification and the HAQ score in BD.</div></div><div><h3>Results</h3><div>A total of 617 patients were studied. These were defined as 0.1&gt;Vxy as remission (REM), 0.45&gt;Vxy≥0.1 and 0.125≥Vz as low joint activity (LJA), 1.0&gt;Vxy≥0.45 or 0.45&gt;Vxy and Vz&gt;0.125 as moderate joint activity (MJA), and Vxy≥1.0 was defined as high joint activity (HJA). The external big dataset consists of 11,013 RA patients. Vxy and the SDAI score correlated significantly <em>(p</em> &lt; 0.0001). Mean values of SDAI and HAQ-DI increase stepwise as the criteria upgrade. It has been suggested that JIV may be able to pick up patients at risk of being missed by SDAI when large joints are involved.</div></div><div><h3>Conclusions</h3><div>JIV has been assessed and verified for its appropriateness, unbiased evaluation of the joints, and advantages in covering an unmet need in SDAI.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152659"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521253","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}
引用次数: 0
The prognostic power of anti-topoisomerase I and anti-centromere antibodies in systemic sclerosis - A systematic review of the literature
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152667
E.M. Hoekstra , S.I.E. Liem , M. Boonstra , C.M. Fehres , J.W. Schoones , T.W.J. Huizinga , J.K. de Vries-Bouwstra
{"title":"The prognostic power of anti-topoisomerase I and anti-centromere antibodies in systemic sclerosis - A systematic review of the literature","authors":"E.M. Hoekstra ,&nbsp;S.I.E. Liem ,&nbsp;M. Boonstra ,&nbsp;C.M. Fehres ,&nbsp;J.W. Schoones ,&nbsp;T.W.J. Huizinga ,&nbsp;J.K. de Vries-Bouwstra","doi":"10.1016/j.semarthrit.2025.152667","DOIUrl":"10.1016/j.semarthrit.2025.152667","url":null,"abstract":"<div><h3>Background</h3><div>Anti-topoisomerase I antibodies (ATA) and anti-centromere antibodies (ACA) are the most prevalent systemic sclerosis (SSc) specific antibodies and are associated with distinct clinical phenotypes. This study reviews the prognostic potential of these autoantibodies for disease specific complications.</div></div><div><h3>Methods</h3><div>Literature searches of PubMed (MEDLINE), Embase, Web of Science and Cochrane Library were performed to identify longitudinal SSc-studies, reporting on the prognostic value of ATA and ACA for any aspect of survival or disease complications. After full text review, studies with &lt;30 events of interest, &lt;30 ACA positive and/or ATA positive patients, and with a moderate to high risk of bias (according to the QUIPS risk of bias tool) were excluded.</div></div><div><h3>Results</h3><div>Of 872 retrieved articles, 43 fulfilled the inclusion criteria. The included studies showed great heterogeneity in baseline characteristics and study design: mean baseline disease duration varied from 1 to 12 years and follow-up duration ranged from 1 to 18.1 years. One of the 21 studies found that ATA has prognostic value for mortality. Five of the nineteen available studies observed higher survival rates for ACA positive patients. Future development of ILD was associated with ATA in four of the seven studies, whereas ACA was associated with lower risk of ILD development in three out of four studies. For other disease outcomes, data are scarce.</div></div><div><h3>Conclusion</h3><div>In conclusion, there is little sound evidence to support an independent prognostic value of ATA and ACA for mortality in SSc. ATA is associated with future ILD development, while ACA decreases the risk of ILD development. To determine the possible role of ATA and/or ACA as biomarkers for every day clinical management and trial enrichment, future studies are warranted in well described cohorts in early SSc.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152667"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534126","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}
引用次数: 0
What outcomes are important to people with foot and ankle disorders in rheumatic and musculoskeletal diseases? An OMERACT qualitative interview study across four continents
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152671
Lara S. Chapman , Caroline A. Flurey , Pamela Richards , Anthony C. Redmond , Eiman Soliman , Abdelhfeez Moshrif , Lucy Malone , Christopher Joyce , John B. Arnold , Yvonne M. Golightly , Catherine Hofstetter , Philip S. Helliwell , Hylton B. Menz , Marian T. Hannan , Md Nazibur Rahman , Beverley J. Shea , Toby O. Smith , Heidi J. Siddle
{"title":"What outcomes are important to people with foot and ankle disorders in rheumatic and musculoskeletal diseases? An OMERACT qualitative interview study across four continents","authors":"Lara S. Chapman ,&nbsp;Caroline A. Flurey ,&nbsp;Pamela Richards ,&nbsp;Anthony C. Redmond ,&nbsp;Eiman Soliman ,&nbsp;Abdelhfeez Moshrif ,&nbsp;Lucy Malone ,&nbsp;Christopher Joyce ,&nbsp;John B. Arnold ,&nbsp;Yvonne M. Golightly ,&nbsp;Catherine Hofstetter ,&nbsp;Philip S. Helliwell ,&nbsp;Hylton B. Menz ,&nbsp;Marian T. Hannan ,&nbsp;Md Nazibur Rahman ,&nbsp;Beverley J. Shea ,&nbsp;Toby O. Smith ,&nbsp;Heidi J. Siddle","doi":"10.1016/j.semarthrit.2025.152671","DOIUrl":"10.1016/j.semarthrit.2025.152671","url":null,"abstract":"<div><h3>Background</h3><div>The foot and ankle are frequently affected in rheumatic and musculoskeletal diseases (RMDs), yet there is a lack of high-quality evidence to determine the effectiveness of treatments. Outcomes in research are often inconsistently measured, impeding evidence synthesis. Additionally, clinical decisions are based on research outcomes, but these are not always regarded as important by people with RMDs. This study aimed to determine domains of importance to people with RMDs who have experienced foot and ankle disorders, and aid in developing a standardised core outcome set (COS) to address these issues.</div></div><div><h3>Methods</h3><div>Participants from four continents (Europe, Africa, Australia, North America) were recruited to semi-structured interviews through clinical departments and electronic mailing lists. Analysis was conducted using a mixed deductive/inductive approach to the framework method. Patient research partners co-produced the interview schedule and recruitment materials, and co-interpreted results.</div></div><div><h3>Results</h3><div>Fifty-six participants (age range 27 to 76 years; 66 % female), with foot and ankle disorders in a variety of RMDs (including inflammatory arthritis, osteoarthritis, crystal arthropathies, connective tissue diseases), were interviewed. Sixteen domains were described by participants: pain, physical function, fatigue, deformity, skin and nail health, swelling, temperature, numbness, poor circulation, cramping, activities/participation, footwear impact, psychological impact, sleep, healthcare utilisation and personal expenses. Most domains were considered important to participants regardless of RMD or geographic location.</div></div><div><h3>Conclusions</h3><div>Foot and ankle disorders have far-reaching consequences for people with RMDs. This large qualitative study provides a foundation for achieving international consensus on a core outcome set for foot and ankle disorders in RMDs, to improve the quality of evidence demonstrating effectiveness of treatments.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152671"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510127","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}
引用次数: 0
Quantifying and improving rheumatoid arthritis algorithm performance in biobank settings
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152668
Vanessa L. Kronzer , Katrina A. Williamson , Andrew C. Hanson , Jennifer A. Sletten , Jeffrey A. Sparks , John M. Davis III , Cynthia S. Crowson
{"title":"Quantifying and improving rheumatoid arthritis algorithm performance in biobank settings","authors":"Vanessa L. Kronzer ,&nbsp;Katrina A. Williamson ,&nbsp;Andrew C. Hanson ,&nbsp;Jennifer A. Sletten ,&nbsp;Jeffrey A. Sparks ,&nbsp;John M. Davis III ,&nbsp;Cynthia S. Crowson","doi":"10.1016/j.semarthrit.2025.152668","DOIUrl":"10.1016/j.semarthrit.2025.152668","url":null,"abstract":"<div><h3>Objective</h3><div>To quantify and improve the performance of standard rheumatoid arthritis (RA) algorithms in a biobank setting.</div></div><div><h3>Methods</h3><div>This retrospective cohort study within the Mayo Clinic (MC) Biobank and MC Tapestry Study identified RA cases by presence of at least two RA codes OR positive anti-cyclic citrullinated peptide antibodies (CCP) plus disease-modifying anti-rheumatic drug (DMARD) prescription as of 7/18/2022. Rheumatology physicians manually verified all RA cases using RA criteria and/or rheumatology physician diagnosis plus DMARD use. All other biobank participants served as non-RA controls. We defined seropositivity as rheumatoid factor and/or anti-CCP positivity. We assessed rules-based and Electronic Medical Records and Genomics (eMERGE) RA algorithms using positive predictive value (PPV). Finally, we developed a novel RA algorithm using a LASSO-based machine learning approach with five-fold cross validation.</div></div><div><h3>Results</h3><div>We identified 1,316 confirmed RA cases (968 MC Biobank, 348 Tapestry, 70 % seropositive) and 82,123 non-RA controls (mean age 65, 61 % female). The PPV of 3 RA codes was 43 %, codes plus DMARD was 54 %, and codes plus DMARD plus seropositivity was 85 %. The PPV of eMERGE was 77 %. Available in the MC Biobank, self-reported RA (PPV 10 %) only minimally improved algorithm performance (PPV from 83 % to 85 %), whereas family history of RA (PPV 3 %) worsened performance. At 90 % PPV, the novel RA algorithm incorporating key variables such as anti-CCP and DMARD use increased sensitivity by 4–11 % compared to eMERGE.</div></div><div><h3>Conclusion</h3><div>Rules-based and eMERGE RA algorithms had worse performance in biobank than administrative settings. Our novel RA algorithm outperformed these standard algorithms.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152668"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521206","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}
引用次数: 0
Exposure-response relationship of mycophenolic acid in pediatric lupus nephritis patients receiving multi-target therapy: An observational cohort study
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152674
Lizhi Chen , Lu Zhang , Baojing Liu , Xiaohong Liu , Zhijun Huang , Kejing Tang , Pan Chen , Xiaoyun Jiang
{"title":"Exposure-response relationship of mycophenolic acid in pediatric lupus nephritis patients receiving multi-target therapy: An observational cohort study","authors":"Lizhi Chen ,&nbsp;Lu Zhang ,&nbsp;Baojing Liu ,&nbsp;Xiaohong Liu ,&nbsp;Zhijun Huang ,&nbsp;Kejing Tang ,&nbsp;Pan Chen ,&nbsp;Xiaoyun Jiang","doi":"10.1016/j.semarthrit.2025.152674","DOIUrl":"10.1016/j.semarthrit.2025.152674","url":null,"abstract":"<div><h3>Objective</h3><div>To establish the effectiveness threshold of mycophenolic acid-area under the concentration-time curve between 0 h and 12 h (MPA-AUC<sub>0–12</sub> <sub>h</sub>) in pediatric lupus nephritis (LN) patients receiving multi-target therapy.</div></div><div><h3>Methods</h3><div>This observational cohort study enrolled 48 pediatric LN patients treated with mycophenolate mofetil (MMF), tacrolimus, and prednisone. MPA-AUC<sub>0–12</sub> <sub>h</sub> was calculated using concentrations based on a limited sampling strategy. Binary logistic regression analysis was employed to investigate factors influencing efficacy. Receiver operating characteristic analysis was conducted to assess MPA-AUC<sub>0–12</sub> <sub>h</sub> threshold values. The cumulative incidence of renal remission and inactive systemic lupus erythematosus (SLE) over time was evaluated using Kaplan-Meier analysis. The <em>t</em>-test or Mann-Whitney test was utilized for comparisons between two groups of continuous variables.</div></div><div><h3>Results</h3><div>To achieve renal remission, the MPA-AUC<sub>0–12</sub> <sub>h</sub> threshold at 6 months was determined to be 25.24 μg·h·mL⁻¹, with an area under the ROC curve (AUC) of 0.83 (<em>P</em> = 0.0002). At 12 months, the MPA-AUC threshold decreased to 23.52 μg·h·mL⁻¹, yielding an AUC of 0.89 (<em>P</em> &lt; 0.0001). For inactive SLE, the MPA-AUC<sub>0–12</sub> <sub>h</sub> threshold at 6 months was found to be 31.16 μg·h·mL⁻¹, with an AUC of 0.80 (<em>P</em> = 0.0004), while at 12 months it decreased slightly to 28.87 μg·h·mL⁻¹, resulting in an AUC of 0.82 (<em>P</em> = 0.0012). Patients who reached target thresholds for MPA-AUC<sub>0–12</sub> <sub>h</sub> achieved renal response or inactive SLE more rapidly.</div></div><div><h3>Conclusion</h3><div>There is a significant correlation between MPA-AUC<sub>0–12</sub> <sub>h</sub> and treatment response in pediatric LN patients receiving multi-target therapy; therefore, it is recommended that MMF dosing be adjusted according to individual MPA-AUC<sub>0–12</sub> <sub>h</sub> levels.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152674"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521184","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}
引用次数: 0
Regulation of T peripheral helper and T follicular helper cells in lupus.
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152675
Deepak A Rao
{"title":"Regulation of T peripheral helper and T follicular helper cells in lupus.","authors":"Deepak A Rao","doi":"10.1016/j.semarthrit.2025.152675","DOIUrl":"https://doi.org/10.1016/j.semarthrit.2025.152675","url":null,"abstract":"","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":" ","pages":"152675"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537622","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}
引用次数: 0
Bruton's tyrosine kinase - A new target for immune mediated inflammatory diseases?
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-22 DOI: 10.1016/j.semarthrit.2025.152681
John D Isaacs
{"title":"Bruton's tyrosine kinase - A new target for immune mediated inflammatory diseases?","authors":"John D Isaacs","doi":"10.1016/j.semarthrit.2025.152681","DOIUrl":"https://doi.org/10.1016/j.semarthrit.2025.152681","url":null,"abstract":"<p><p>Bruton's tyrosine kinase (BTK) is a cytoplasmic protein that plays a key role in signalling pathways downstream of diverse surface receptors in B-cells and myeloid cells. These include the B-cell receptor itself, Fc receptors including FcεRI, toll-like receptors and chemokine receptors. Congenital deficiency of BTK causes X-linked agammaglobulinaemia because of B-cell developmental block, and BTK inhibitors (BTKi) are approved for the treatment of certain B-cell malignancies. They have also been studied in a variety of autoimmune and inflammatory diseases. In rheumatic conditions, results have been disappointing in rheumatoid arthritis (RA) and systemic lupus erythematosus but with some evidence for efficacy in Sjogren's syndrome. Data are more positive in multiple sclerosis, as well as in the cutaneous disease chronic spontaneous urticaria and possibly pemphigus vulgaris. BTKi may also find a role in severe allergic disease such as food allergy. First generation BTKi had a safety profile that included cardiotoxicity, hypertension, haemorrhage and rash. Second generation inhibitors have a more acceptable safety profile although dose-limiting toxicity is still observed in some conditions, including RA. Pharmacokinetic factors aside, the variable efficacy in different diseases is not fully explained but is likely to reflect disease dependence on different pathways in B-cells and myeloid cells and their relative sensitivity to BTKi.</p>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":" ","pages":"152681"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537697","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}
引用次数: 0
The Fifth Element: Is Vascular Dysfunction an Intrinsic Feature of Gout?
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-21 DOI: 10.1016/j.semarthrit.2025.152679
Michael H Pillinger, Michael Toprover
{"title":"The Fifth Element: Is Vascular Dysfunction an Intrinsic Feature of Gout?","authors":"Michael H Pillinger, Michael Toprover","doi":"10.1016/j.semarthrit.2025.152679","DOIUrl":"10.1016/j.semarthrit.2025.152679","url":null,"abstract":"<p><p>Gout, the most common inflammatory arthritis, affects as many as 5.1% of the adult population. Classically, gout is conceived as four sequential phenotypic states: 1) asymptomatic hyperuricemia 2) acute gout flare 3) inter-critical gout (gout between flares); and 4) tophaceous gout. However, these four states are paralleled by a fifth state, consisting of vascular involvement. The mechanisms and consequences of vascular gout are incompletely elucidated. In vitro and animal models indicate that soluble urate adversely affects vascular endothelium and smooth muscle. The recent discovery that soluble urate can be transported intracellularly to alter cell metabolism and epigenetics (trained innate immunity) suggests additional impacts of urate on leukocytes and endothelium. Once gout has progressed to flares, the vasculature is exposed to inflammatory mediators, both during flares and to a lesser but persistent extent inter-critically, suggesting additional mechanisms of gout's effect. We have reported that patients with gout have diminished endothelial function measured by brachial artery flow-mediated dilation. ACR gout guideline-concordant treatment improves endothelial function but is less effective in patients with cardiometabolic comorbidities. Moreover, treatment of gout patients with the anti-inflammatory colchicine and urate lowering therapy improves endothelial function and reduces the risk of both incident coronary artery disease (CAD), and MACE in patients with established CAD.</p>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":" ","pages":"152679"},"PeriodicalIF":4.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531742","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}
引用次数: 0
Sodium-glucose cotransporter 2 (SGLT2) inhibition and autoimmunity.
IF 4.6 2区 医学
Seminars in arthritis and rheumatism Pub Date : 2025-02-21 DOI: 10.1016/j.semarthrit.2025.152663
Andreas Kronbichler
{"title":"Sodium-glucose cotransporter 2 (SGLT2) inhibition and autoimmunity.","authors":"Andreas Kronbichler","doi":"10.1016/j.semarthrit.2025.152663","DOIUrl":"https://doi.org/10.1016/j.semarthrit.2025.152663","url":null,"abstract":"<p><p>The approval of sodium-glucose cotransporter (SGLT2) inhibitors has revolutionized the management of patients with diabetes, heart failure and especially those with chronic kidney disease (CKD). Beyond development of CKD, patients with autoimmune disorders have an increased cardiovascular morbidity and mortality. Therefore, this patient population would benefit the most from effective therapies to reduce this burden, and secondly, slowing of CKD progression to reduce the frequency of kidney failure. Patients with systemic autoimmune disorders, such as systemic lupus erythematosus with lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis were excluded from the DAPA-CKD trial, and higher doses of glucocorticoids or intravenous use of immunosuppression within 3 months were exclusion criteria of the EMPA-KIDNEY trial. Thus, these agents remain untested in patients with active autoimmune kidney diseases in a systematic way, and this gap is unlikely to be filled by high-quality randomized clinical trials. Beyond having nephro- and cardioprotective effects, SGLT2i have shown in vivo and in vitro efficacy to manage autoimmunity in SLE, LN and rheumatoid arthritis (RA). These effects need to be confirmed in humans, but might provide a further rationale for the use of these potent drugs. The safety profile is in general favourable, but \"sick day rules\" need to be followed in order to avoid serious side effects.</p>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":" ","pages":"152663"},"PeriodicalIF":4.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524431","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}
引用次数: 0
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