{"title":"The Autoantibody response in rheumatoid arthritis; what makes it unique?","authors":"Rene E.M. Toes","doi":"10.1016/j.semarthrit.2025.152699","DOIUrl":"10.1016/j.semarthrit.2025.152699","url":null,"abstract":"<div><div>Many autoimmune diseases respond well to therapies targeting B cells, emphasizing the importance of autoreactive B cells in disease induction and progression. In some cases, autoantibodies from plasma cells are the main effectors, while in others, memory B cells are thought to modulate inflammatory responses through antigen presentation or cytokine secretion. Tolerance mechanisms usually prevent the development of autoantibodies, but when these systems fail, autoimmunity and subsequent autoimmune diseases can arise. Understanding the dynamics of autoreactive B cell responses is crucial for delineation the pathogenic pathways underlying disease. Rheumatoid arthritis (RA) is a prototypic autoimmune disease featuring autoreactive B cell responses against post-translationally modified (PTM) proteins. Especially, the Anti-Citrullinated Protein Antibody (ACPA) response, the autoimmune response hallmarking RA, is well characterized over the last two decades. ACPA target citrullinated proteins and their presence is associated with more severe disease progression. In recent years, it has become apparent that ACPA are very promiscuous and able to recognize both human and microbial PTM proteins. Likewise, it is now clear that these antibodies often carry Fab glycans that could, potentially, boost B cell activation and/or be involved in evasion of tolerance mechanisms. Although subjected to tolerance checkpoint, new technologies have shown that the secreted ACPA repertoire is highly polyclonal, unique to each patient, but also dominated by a few ACPA clones.</div><div>In this synopsis, these and other findings are discussed. Overall, these shed light on the complexity and evolving nature of the ACPA response in RA, unveiling new insights into autoreactive B cell behavior.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152699"},"PeriodicalIF":4.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568073","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}
{"title":"Distinct appearances of circulatory and secretory IgM demarcated by CD5L","authors":"Albert J.R. Heck","doi":"10.1016/j.semarthrit.2025.152683","DOIUrl":"10.1016/j.semarthrit.2025.152683","url":null,"abstract":"<div><div>IgM is an important human immunoglobulin present in our blood, but also in mucosa and body fluids such as saliva, tears and breast milk. In this manuscript Heck describes recent findings, namely that the CD5L protein is always attached to circulatory IgM but not to secretory IgM</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152683"},"PeriodicalIF":4.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557518","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}
{"title":"B suppressor cells and protective autoantibodies","authors":"Rikard Holmdahl","doi":"10.1016/j.semarthrit.2025.152687","DOIUrl":"10.1016/j.semarthrit.2025.152687","url":null,"abstract":"<div><div>Recently the importance of B cells has been highlighted for therapy of several autoimmune diseases including rheumatoid arthritis (RA). Still, the functional role of B cells and antibodies in the disease process are unclear. Using animal models, antibodies specifically binding cartilage are pathogenic, but it has also recently been shown that both B cells and antibodies could be protective. These have specificities that are similar to B cells and autoantibodies detected in humans, including antibodies to citrullinated proteins and collagen type II, and may play an important role hindering an inflammatory attack, whereafter pathogenic B cells and antibodies are functionally more important to initiate and drive the clinically observable disease.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152687"},"PeriodicalIF":4.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573962","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}
{"title":"Targeting the Wnt pathway for the treatment of Osteoarthritis of the knee","authors":"Nancy E. Lane","doi":"10.1016/j.semarthrit.2025.152662","DOIUrl":"10.1016/j.semarthrit.2025.152662","url":null,"abstract":"<div><div>Both epidemiologic and preclinical models of OA provide strong support for modulation of the Wnt signaling pathway as a druggable target for painful knee OA. This paper reviews the clinical studies that have been performed with Wnt signaling modulating agents for knee OA treatment and makes recommendations to study earlier disease and administer treatments for a longer duration.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152662"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586823","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}
{"title":"Probing the synovium-brain axis","authors":"Neil Basu","doi":"10.1016/j.semarthrit.2025.152673","DOIUrl":"10.1016/j.semarthrit.2025.152673","url":null,"abstract":"","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152673"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557470","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}
{"title":"Hematopoietic stem cell transplant, chimeric antigen receptor T-cells, and other cellular therapies as stepping stones toward long-term improvement in severe scleroderma and other autoimmune diseases","authors":"Keith M. Sullivan","doi":"10.1016/j.semarthrit.2025.152676","DOIUrl":"10.1016/j.semarthrit.2025.152676","url":null,"abstract":"<div><div>Preclinical models of inherited and induced autoimmune diseases (AIDs) have shown that hematopoietic stem cell transplantation (HSCT) following high-dose immunosuppressive conditioning could reverse organ damage and alter the course of AIDs. The rationale for both autologous and allogeneic HSCT has been based upon a reset of the immune system. Clinical application of HSCT was initially focused on severe systemic sclerosis (SSc) and three randomized trials comparing autologous HSCT with standard cyclophosphamide (CY) demonstrated significant improvement in SSc measured 12-54 months after transplant. Meta-analysis of the three trials showed the relative risk of all-cause mortality after HSCT was 0.5 compared to CY. More recently, clinical improvements in several AIDs have been reported with CY/fludarabine preparation followed by CD19 chimeric antigen receptor (CAR) T-cell infusion. With follow-up of 4-29 months, major disease responses and full B-cell reconstitution have been observed while side effects have been modest. Industry and academic centers are active in developing these and other cellular products for AID treatments including CAR-NK, off the shelf CAR-Ts, chimeric autoantibody receptor (CAAR-Ts), and mesenchymal stromal cells (MSCs). Clinical improvements after MSC administration have been reported, but as with the CAR-T trials, follow-up is still brief. Shared decision making with patients considering cellular therapy is perhaps easier for autologous HSCT since we have longer follow-up with many patients clinically improved and surviving off DMARDS for decades. Such individuals understandably view themselves as cured. Thus, the interest in the evolving role of cellular therapies in long-term improvement in severe AIDs.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152676"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586798","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}
Amelia Ruffatti , Marta Tonello , Maria Favaro , Teresa Del Ross , Antonia Calligaro , Ariela Hoxha , Giovanni Peronato , Cesarina Facchini , Margherita Zen , Renzo Manara
{"title":"Risk and triggering factors for diffuse alveolar hemorrhage in primary antiphospholipid syndrome. An observational follow-up study and a systematic review of the literature","authors":"Amelia Ruffatti , Marta Tonello , Maria Favaro , Teresa Del Ross , Antonia Calligaro , Ariela Hoxha , Giovanni Peronato , Cesarina Facchini , Margherita Zen , Renzo Manara","doi":"10.1016/j.semarthrit.2025.152697","DOIUrl":"10.1016/j.semarthrit.2025.152697","url":null,"abstract":"<div><h3>Background</h3><div>Diffuse alveolar hemorrhage (DAH) represents a serious, life-threatening complication of primary antiphospholipid syndrome (PAPS), a thrombophilic disorder mainly characterized by vascular thrombosis and/or pregnancy morbidity. Risk factors for DAH in PAPS patients and the comorbidities that may trigger DAH were investigated here in the effort to identify possible independent predictors of DAH in PAPS patients.</div></div><div><h3>Methods</h3><div>Only PAPS patients fulfilling the Sydney criteria were taken into consideration. The DAH diagnosis was based on the patient's clinical presentation (acute illness manifesting with dyspnoea, hypoxia, cough, anemia and less frequently hemoptysis and fever), the presence of transient lung infiltrates on chest radiographs, a rapidly changing ground-glass appearance on computed tomography, and a positive response to high dose steroid therapy prescribed during an acute phase. The PAPS patients manifesting DAH signs and symptoms were considered the study group; the remaining served as the control group. The following comorbidities were investigated: i) left-sided heart valve diseases, ii) left heart failure and iii) hemolytic anemia. The clinical and laboratory characteristics and comorbidities of the PAPS-associated DAH patients were recorded and compared with those of the control group and those of the PAPS-associated DAH patients identified by a literature review.</div></div><div><h3>Results</h3><div>The subjects considered for inclusion were 197 PAPS patients (142 women and 55 men) all suffering from thrombosis, which was associated with pregnancy morbidity in 30 (21.1 %) of the women. Eight (4.1 %) of these patients (five men and three women) experienced one or more episodes of DAH. When the clinical and laboratory characteristics of the PAPS-associated DAH patients were compared with those of the controls a significant prevalence of the male gender (<em>p</em> = 0.0399), of the multiple types of vascular involvement profile (<em>p</em> = 0.0048) and of high antiphospholipid antibody (aPL) titers (<em>p</em> = 0.0011) was noted in the former. Triple aPL positivity and microcirculation thrombosis were also more frequent in that group, although not to a significant degree. The prevalence of comorbidities including left-sided heart valve diseases, left heart failure and hemolytic anemia was likewise significantly higher in the PAPS-associated DAH patients (<em>p</em> = 0.0253, 0.0451 and 0.0358, respectively). According to logistic regression analysis, multiple types of vascular involvement profile, left-sided heart valve diseases and hemolytic anemia were found to be independent risk factors for DAH (<em>p</em> = 0.030, 0.022 and 0.007, respectively). Twenty-four studies (one case-control, three small case series, and 20 case reports) reporting on 55 PAPS-associated DAH patients were identified by a review of the literature. The clinical and laboratory characteristics and comorb","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152697"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563859","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}
Yiling Zhang , Sara K. Tedeschi , Abhishek Abhishek , Owen Hensey , David Grossberg , Ken Cai , Beverley Shea , Jasvinder A. Singh , Robin Christensen , Teodora Serban , Edoardo Cipolletta , Konstantinos Parperis , Cesar Diaz-Torne , Geraldine M McCarthy , Fabio Becce , Tamer A Gheita , Silvia Sirotti , Sara Nysom Christiansen , Luis Coronel , Lisa K Stamp , Nicola Dalbeth
{"title":"Core domain set for studies of acute calcium pyrophosphate crystal arthritis: OMERACT delphi survey to establish consensus","authors":"Yiling Zhang , Sara K. Tedeschi , Abhishek Abhishek , Owen Hensey , David Grossberg , Ken Cai , Beverley Shea , Jasvinder A. Singh , Robin Christensen , Teodora Serban , Edoardo Cipolletta , Konstantinos Parperis , Cesar Diaz-Torne , Geraldine M McCarthy , Fabio Becce , Tamer A Gheita , Silvia Sirotti , Sara Nysom Christiansen , Luis Coronel , Lisa K Stamp , Nicola Dalbeth","doi":"10.1016/j.semarthrit.2025.152670","DOIUrl":"10.1016/j.semarthrit.2025.152670","url":null,"abstract":"<div><h3>Objective</h3><div>To identify potential domains for the Outcome Measures in Rheumatology (OMERACT) core domain set for studies of an individual flare of acute calcium pyrophosphate (CPP) crystal arthritis.</div></div><div><h3>Methods</h3><div>Patient research partners (PRPs) and other participants (mainly clinicians and researchers) completed three rounds of survey using Delphi methodology. Consensus was defined as ≥ 70 % of both PRP and other participants groups rated the domain as a ‘critically important domain to include’. In a subsequent ranking exercise, all participants were asked to rank and comment on up to 10 domains to include as core domains.</div></div><div><h3>Results</h3><div>Fourteen domains reached consensus as critically important in the Delphi survey. In the Pathophysiological Manifestations area, the domains were joint pain, joint tenderness, joint swelling, joint inflammation on imaging tests and duration of acute CPP crystal arthritis flare. In the Life Impact area, the domains were overall function, ability to complete daily tasks, ability to work, health related quality of life, patient global assessment response to treatment, patient and physician global assessments of disease activity, and patient satisfaction with treatment. In the Societal/Resource Use area, use of rescue medications reached consensus. In the ranking exercise, joint pain, joint tenderness, joint swelling, overall function and ability to complete daily tasks ranked highest.</div></div><div><h3>Conclusion</h3><div>Joint pain, joint swelling, joint tenderness, duration of acute CPP crystal arthritis flare, overall function, ability to complete daily tasks, and patient global assessment of disease activity received the strongest support to be included in the OMERACT core domain set for studies of acute CPP crystal arthritis.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152670"},"PeriodicalIF":4.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534127","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}
Javier Llorca , Iván Ferraz-Amaro , Santos Castañeda , Enrique Raya , Luis Rodríguez-Rodríguez , Sergio Rodríguez-Montero , Ginés Sánchez-Nievas , Antonio López-Meseguer , Zulema Plaza , Fernando Sánchez-Alonso , Carmen García-Gómez , Carlos González-Juanatey , Miguel Ángel González-Gay
{"title":"Evaluating the reliability of cardiovascular risk scales in patients with chronic inflammatory rheumatic diseases","authors":"Javier Llorca , Iván Ferraz-Amaro , Santos Castañeda , Enrique Raya , Luis Rodríguez-Rodríguez , Sergio Rodríguez-Montero , Ginés Sánchez-Nievas , Antonio López-Meseguer , Zulema Plaza , Fernando Sánchez-Alonso , Carmen García-Gómez , Carlos González-Juanatey , Miguel Ángel González-Gay","doi":"10.1016/j.semarthrit.2025.152694","DOIUrl":"10.1016/j.semarthrit.2025.152694","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the performance of the QRESEARCH risk estimator version 3 (QRISK3), the Systematic COronary Risk Evaluation (SCORE) 2, and Predicting Risk of cardiovascular disease EVENTs (PREVENT) equationin a cohort of individuals with chronic inflammatory rheumatic diseases (CIRD) enrolled in the Spanish prospective CARdiovascular in RheuMAtology (CARMA) project.</div></div><div><h3>Methods</h3><div>Between July 2010 and January 2012, the study recruited CIRD patients from 67 hospitals across Spain. It included individuals diagnosed with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. At the 10-year follow-up, data for all patients included in the initial cohort were assessed. We estimated four 10-year cardiovascular disease (CVD) incidence risk scores using data recorded at recruitment.</div></div><div><h3>Results</h3><div>2080 patients were included in this analysis. QRISK3 and PREVENT-CVD predicted an average of approximately 10 % CV events across the entire cohort, while SCORE2 and PREVENT-Atherosclerotic Cardiovascular Disease (ASCVD) predicted an average of only 6.3 %. The linear correlation coefficients between each pair of scales were consistently above 0.8, with an average of 0.9074. Notably, lower correlations were observed between QRISK3 and the other scales. When identifying patients with higher CV risk, the kappa index was higher between SCORE2, PREVENT-CVD, and PREVENT-ASCVD than between QRISK3 and any other scale. These findings suggest that most patients identified as high-risk by SCORE2 would also be classified as high-risk when using PREVENT-CVD or PREVENT-ASCVD.</div></div><div><h3>Conclusions</h3><div>The higher correlation and reliability observed between SCORE2, PREVENT-CVD, and PREVENT-ASCVD in our series of CIRD patients followed over a 10-year period suggest that these scales may be largely interchangeable for identifying high-risk CIRD patients.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152694"},"PeriodicalIF":4.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563860","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}
{"title":"Targeting the Wnt pathway for the treatment of Osteoarthritis of the knee","authors":"Nancy E. Lane","doi":"10.1016/j.semarthrit.2025.152680","DOIUrl":"10.1016/j.semarthrit.2025.152680","url":null,"abstract":"","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"72 ","pages":"Article 152680"},"PeriodicalIF":4.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537625","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}