Pub Date : 2024-05-21DOI: 10.1016/j.autrev.2024.103574
Shuang Xu , William F. Jiemy , Elisabeth Brouwer , Janette K. Burgess , Peter Heeringa , Kornelis S.M. van der Geest , Roser Alba-Rovira , Marc Corbera-Bellalta , Annemieke H. Boots , Maria C. Cid , Maria Sandovici
Large-vessel vasculitides (LVV) comprise a group of chronic inflammatory diseases of the aorta and its major branches. The most common forms of LVV are giant cell arteritis (GCA) and Takayasu arteritis (TAK). Both GCA and TAK are characterized by granulomatous inflammation of the vessel wall accompanied by a maladaptive immune and vascular response that promotes vascular damage and remodeling. The inflammatory process in LVV starts in the adventitia where fibroblasts constitute the dominant cell population. Fibroblasts are traditionally recognized for synthesizing and renewing the extracellular matrix thereby being major players in maintenance of normal tissue architecture and in tissue repair. More recently, fibroblasts have emerged as a highly plastic cell population exerting various functions, including the regulation of local immune processes and organization of immune cells at the site of inflammation through production of cytokines, chemokines and growth factors as well as cell-cell interaction. In this review, we summarize and discuss the current knowledge on fibroblasts in LVV. Furthermore, we identify key questions that need to be addressed to fully understand the role of fibroblasts in the pathogenesis of LVV.
大血管炎(LVV)是主动脉及其主要分支的一组慢性炎症性疾病。最常见的大血管炎是巨细胞动脉炎(GCA)和高安动脉炎(TAK)。GCA 和 TAK 的特点都是血管壁肉芽肿性炎症,伴有不良的免疫和血管反应,从而促进血管损伤和重塑。左心室血管炎的炎症过程始于前壁,成纤维细胞是前壁的主要细胞群。传统上,成纤维细胞被认为能合成和更新细胞外基质,因此是维持正常组织结构和组织修复的主要角色。最近,成纤维细胞作为一种可塑性极强的细胞群出现,发挥着多种功能,包括通过产生细胞因子、趋化因子和生长因子以及细胞间相互作用,调节局部免疫过程和组织炎症部位的免疫细胞。在这篇综述中,我们总结并讨论了目前有关低密度肺泡中成纤维细胞的知识。此外,我们还指出了需要解决的关键问题,以全面了解成纤维细胞在左心室积液发病机制中的作用。
{"title":"Current evidence on the role of fibroblasts in large-vessel vasculitides: From pathogenesis to therapeutics","authors":"Shuang Xu , William F. Jiemy , Elisabeth Brouwer , Janette K. Burgess , Peter Heeringa , Kornelis S.M. van der Geest , Roser Alba-Rovira , Marc Corbera-Bellalta , Annemieke H. Boots , Maria C. Cid , Maria Sandovici","doi":"10.1016/j.autrev.2024.103574","DOIUrl":"10.1016/j.autrev.2024.103574","url":null,"abstract":"<div><p>Large-vessel vasculitides (LVV) comprise a group of chronic inflammatory diseases of the aorta and its major branches. The most common forms of LVV are giant cell arteritis (GCA) and Takayasu arteritis (TAK). Both GCA and TAK are characterized by granulomatous inflammation of the vessel wall accompanied by a maladaptive immune and vascular response that promotes vascular damage and remodeling. The inflammatory process in LVV starts in the adventitia where fibroblasts constitute the dominant cell population. Fibroblasts are traditionally recognized for synthesizing and renewing the extracellular matrix thereby being major players in maintenance of normal tissue architecture and in tissue repair. More recently, fibroblasts have emerged as a highly plastic cell population exerting various functions, including the regulation of local immune processes and organization of immune cells at the site of inflammation through production of cytokines, chemokines and growth factors as well as cell-cell interaction. In this review, we summarize and discuss the current knowledge on fibroblasts in LVV. Furthermore, we identify key questions that need to be addressed to fully understand the role of fibroblasts in the pathogenesis of LVV.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.1016/j.autrev.2024.103540
Joana Caetano , Luís Monteiro Rodrigues , José Delgado Alves
Objective
Microvascular dysfunction is an early event in the pathogenesis of systemic sclerosis (SSc). The objective of this scoping review is to update the current information and the level of knowledge about the mechanisms of microvascular dysfunction in pre-SSc, very early diagnosis of SSc (VEDOSS) and early SSc.
Methods
A PubMed® database search allowed us to include original data from full-length articles in English in which the main topic was microvascular dysfunction in pre-SSC, VEDOSS or early SSc. Data was extracted using a customized form.
Results
In the present review 437 articles were identified, and 42 studies included, reporting data from a total of 1069 patients with pre-SSc, VEDOSS or early-SSc. Distinct mechanisms of microvascular injury were identified comprising, angiogenesis and vasculogenesis, cell surface proteins and adhesion, molecules expression, cytokines profile, inflammatory and oxidation pathways, and skin perfusion determinants. Most of the studies were conducted in early SSc, with a reduced number in pre-disease stages, in which the prompt recognition of specific mechanisms and biomarkers may allow targeted treatment to prevent disease progression.
Conclusions
Although different molecular expression patterns and signaling pathways related to microvascular dysfunction in pre-SSc, VEDOSS, and early SSc were identified, additional prospective longitudinal studies and combined work with functional evaluation of peripheral skin perfusion are needed.
{"title":"What have we learned on pre, very early, and early systemic sclerosis microcirculatory pathophysiology? A scoping review","authors":"Joana Caetano , Luís Monteiro Rodrigues , José Delgado Alves","doi":"10.1016/j.autrev.2024.103540","DOIUrl":"https://doi.org/10.1016/j.autrev.2024.103540","url":null,"abstract":"<div><h3>Objective</h3><p>Microvascular dysfunction is an early event in the pathogenesis of systemic sclerosis (SSc). The objective of this scoping review is to update the current information and the level of knowledge about the mechanisms of microvascular dysfunction in pre-SSc, very early diagnosis of SSc (VEDOSS) and early SSc.</p></div><div><h3>Methods</h3><p>A PubMed® database search allowed us to include original data from full-length articles in English in which the main topic was microvascular dysfunction in pre-SSC, VEDOSS or early SSc. Data was extracted using a customized form.</p></div><div><h3>Results</h3><p>In the present review 437 articles were identified, and 42 studies included, reporting data from a total of 1069 patients with pre-SSc, VEDOSS or early-SSc. Distinct mechanisms of microvascular injury were identified comprising, angiogenesis and vasculogenesis, cell surface proteins and adhesion, molecules expression, cytokines profile, inflammatory and oxidation pathways, and skin perfusion determinants. Most of the studies were conducted in early SSc, with a reduced number in pre-disease stages, in which the prompt recognition of specific mechanisms and biomarkers may allow targeted treatment to prevent disease progression.</p></div><div><h3>Conclusions</h3><p>Although different molecular expression patterns and signaling pathways related to microvascular dysfunction in pre-SSc, VEDOSS, and early SSc were identified, additional prospective longitudinal studies and combined work with functional evaluation of peripheral skin perfusion are needed.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140554326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1016/j.autrev.2024.103542
Mayka Freire , Bernardo Sopeña , Arturo González-Quintela , Alfredo Guillén del Castillo , Eduardo Callejas Moraga , Gema M. Lledó-Ibañez , Manuel Rubio-Rivas , Luis Trapiella , Ana Argibay , Carles Tolosa , Begoña Marí Alfonso , Jose Antonio Vargas-Hitos , Xavier Pla Salas , Cristina González-Echávarri , Antonio-J Chamorro , Isabel Perales Fraile , Andrés González García , Gloria de la Red Bellvis , David Bernal Bello , Antoni Castro Salomó , Carmen Pilar Simeón-Aznar
{"title":"Exposure to different occupational chemicals and clinical phenotype of a cohort of patients with systemic sclerosis","authors":"Mayka Freire , Bernardo Sopeña , Arturo González-Quintela , Alfredo Guillén del Castillo , Eduardo Callejas Moraga , Gema M. Lledó-Ibañez , Manuel Rubio-Rivas , Luis Trapiella , Ana Argibay , Carles Tolosa , Begoña Marí Alfonso , Jose Antonio Vargas-Hitos , Xavier Pla Salas , Cristina González-Echávarri , Antonio-J Chamorro , Isabel Perales Fraile , Andrés González García , Gloria de la Red Bellvis , David Bernal Bello , Antoni Castro Salomó , Carmen Pilar Simeón-Aznar","doi":"10.1016/j.autrev.2024.103542","DOIUrl":"https://doi.org/10.1016/j.autrev.2024.103542","url":null,"abstract":"","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140543423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rheumatoid arthritis (RA) is the most common form of autoimmune inflammatory arthritis and is associated with various comorbidities including cardiovascular disease (CVD). This scoping review summarizes the current evidence on longitudinal cohort studies assessing potential factors associated with the incidence of cardiovascular events among patients with RA.
Methods
Scopus, PubMed, Ovid MEDLINE and Cochrane databases were used to identify longitudinal cohort studies investigating the incidence of CVD among RA patients. Using predetermined inclusion and exclusion criteria, two reviewers screened and extracted the relevant studies independently to map the existing literature on this topic. The extracted data included study characteristics, demographics, comorbidities, behavioural and RA-related factors.
Results
Thirty-three research papers were included with a mean follow-up duration of 7.8 years. The sample size of the studies ranged from 182 to 4,311,022 subjects, the mean age from 46.1 to 72.3 years, and on average, 34.6% of the participants were male. The following factors were reported to be associated with a higher incidence of CVD in RA patients: older age, male sex, co-morbid hypertension, diabetes, and/or dyslipidemia, the presence of rheumatoid factor (RF) and/or acute phase reactants. Among RA treatments, glucocorticoids were shown to increase CVD incidence while DMARDs, especially methotrexate, were associated with a lower incidence of CVD.
Conclusion
This review offers a comprehensive summary of the current literature reporting on risk factors for CVD incidence among RA patients. Future research should focus on the less studied factors, including socioeconomic status, physical inactivity, alcohol consumption, sleep habits and dietary patterns as well as some RA-related factors such as anti-citrullinated protein antibodies and functional impairment.
导言类风湿性关节炎(RA)是最常见的自身免疫性炎症性关节炎,与包括心血管疾病(CVD)在内的多种合并症有关。本范围综述总结了目前有关纵向队列研究的证据,这些研究评估了与RA患者心血管事件发生率相关的潜在因素。方法使用Scopus、PubMed、Ovid MEDLINE和Cochrane数据库来确定调查RA患者心血管疾病发生率的纵向队列研究。两位审稿人采用预先确定的纳入和排除标准,独立筛选并提取了相关研究,以绘制该主题的现有文献图谱。提取的数据包括研究特征、人口统计学、合并症、行为和 RA 相关因素。研究样本量从182到4,311,022名受试者不等,平均年龄从46.1岁到72.3岁不等,平均34.6%的受试者为男性。据报道,以下因素与RA患者心血管疾病发病率较高有关:年龄较大、男性、合并高血压、糖尿病和/或血脂异常、存在类风湿因子和/或急性期反应物。结论本综述全面总结了目前有关RA患者心血管疾病发病风险因素的文献。未来的研究应关注研究较少的因素,包括社会经济状况、缺乏运动、饮酒、睡眠习惯和饮食模式,以及一些与 RA 相关的因素,如抗瓜氨酸蛋白抗体和功能障碍。
{"title":"Factors associated with incident cardiovascular disease in patients with rheumatoid arthritis: A scoping review","authors":"Yasaman Hajiesmaeili , Preeti Tamhankar , Saverio Stranges , Lillian Barra","doi":"10.1016/j.autrev.2024.103539","DOIUrl":"https://doi.org/10.1016/j.autrev.2024.103539","url":null,"abstract":"<div><h3>Introduction</h3><p>Rheumatoid arthritis (RA) is the most common form of autoimmune inflammatory arthritis and is associated with various comorbidities including cardiovascular disease (CVD). This scoping review summarizes the current evidence on longitudinal cohort studies assessing potential factors associated with the incidence of cardiovascular events among patients with RA.</p></div><div><h3>Methods</h3><p>Scopus, PubMed, Ovid MEDLINE and Cochrane databases were used to identify longitudinal cohort studies investigating the incidence of CVD among RA patients. Using predetermined inclusion and exclusion criteria, two reviewers screened and extracted the relevant studies independently to map the existing literature on this topic. The extracted data included study characteristics, demographics, comorbidities, behavioural and RA-related factors.</p></div><div><h3>Results</h3><p>Thirty-three research papers were included with a mean follow-up duration of 7.8 years. The sample size of the studies ranged from 182 to 4,311,022 subjects, the mean age from 46.1 to 72.3 years, and on average, 34.6% of the participants were male. The following factors were reported to be associated with a higher incidence of CVD in RA patients: older age, male sex, co-morbid hypertension, diabetes, and/or dyslipidemia, the presence of rheumatoid factor (RF) and/or acute phase reactants. Among RA treatments, glucocorticoids were shown to increase CVD incidence while DMARDs, especially methotrexate, were associated with a lower incidence of CVD.</p></div><div><h3>Conclusion</h3><p>This review offers a comprehensive summary of the current literature reporting on risk factors for CVD incidence among RA patients. Future research should focus on the less studied factors, including socioeconomic status, physical inactivity, alcohol consumption, sleep habits and dietary patterns as well as some RA-related factors such as anti-citrullinated protein antibodies and functional impairment.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-31DOI: 10.1016/j.autrev.2024.103537
Kevin D. Deane , Lieve Van Hoovels , Veena E. Joy , Nina Olschowka , Xavier Bossuyt
Autoantibodies are important laboratory markers to support diagnosis of autoimmune diseases. Interpretation of autoantibodies is classically done in a dichotomous way (positive versus negative). Yet, interpretation of autoantibody test results can be improved by reporting likelihood ratios. Likelihood ratios convey information on how much more/less likely a test result is in individuals with the disease compared to individuals without the disease. It incorporates information on the antibody level (the higher the antibody level, the higher the association with the disease), which is helpful for (differential) diagnosis. Likelihood ratios are unit-independent and allow users to harmonize test result interpretation. When the likelihood ratio is combined with information on the pre-test probability, post-test probability can be appraised. In this review, the applicability of likelihood ratio in autoimmune diagnostics will be reviewed from the perspective of the clinician, the laboratory professional and the in vitro diagnostic industry.
{"title":"From autoantibody test results to decision making: Incorporating likelihood ratios within medical practice","authors":"Kevin D. Deane , Lieve Van Hoovels , Veena E. Joy , Nina Olschowka , Xavier Bossuyt","doi":"10.1016/j.autrev.2024.103537","DOIUrl":"https://doi.org/10.1016/j.autrev.2024.103537","url":null,"abstract":"<div><p>Autoantibodies are important laboratory markers to support diagnosis of autoimmune diseases. Interpretation of autoantibodies is classically done in a dichotomous way (positive versus negative). Yet, interpretation of autoantibody test results can be improved by reporting likelihood ratios. Likelihood ratios convey information on how much more/less likely a test result is in individuals with the disease compared to individuals without the disease. It incorporates information on the antibody level (the higher the antibody level, the higher the association with the disease), which is helpful for (differential) diagnosis. Likelihood ratios are unit-independent and allow users to harmonize test result interpretation. When the likelihood ratio is combined with information on the pre-test probability, post-test probability can be appraised. In this review, the applicability of likelihood ratio in autoimmune diagnostics will be reviewed from the perspective of the clinician, the laboratory professional and the in vitro diagnostic industry.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-29DOI: 10.1016/j.autrev.2024.103538
Meng-Di Zhang , Wan-Ying Huang , Jia-Yuan Luo , Rong-Quan He , Zhi-Guang Huang , Jian-Di Li , Fang Qin , Gang Chen , Ling Lei
Objective
This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry.
Methods
Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots.
Results
From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020–2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. Arthritis and Rheumatism was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations.
Conclusion
In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.
{"title":"The ‘whole landscape’ of research on systemic sclerosis over the past 73 years","authors":"Meng-Di Zhang , Wan-Ying Huang , Jia-Yuan Luo , Rong-Quan He , Zhi-Guang Huang , Jian-Di Li , Fang Qin , Gang Chen , Ling Lei","doi":"10.1016/j.autrev.2024.103538","DOIUrl":"10.1016/j.autrev.2024.103538","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry.</p></div><div><h3>Methods</h3><p>Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots.</p></div><div><h3>Results</h3><p>From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020–2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. <em>Arthritis and Rheumatism</em> was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations.</p></div><div><h3>Conclusion</h3><p>In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28DOI: 10.1016/j.autrev.2024.103536
Marie-Elise Martel , Amélie Leurs , David Launay , Hélène Behal , Aurélien Chepy , Aurore Collet , Sébastien Sanges , Eric Hachulla , Sylvain Dubucquoi , Luc Dauchet , Vincent Sobanski
Objectives
Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort.
Methods
Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719).
Findings
In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]).
Interpretation
Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
目的通过对已发表的报告和法国队列的新数据进行系统回顾和荟萃分析,估计抗Ro52-kDa/SSA(TRIM21)自身抗体在系统性硬化症(SSc)中的全球流行率,并描述相关的临床表型:在一项横断面研究中评估了抗-TRIM21血清阳性和相关的SSc特征,研究对象包括里尔大学医院的300名患者。我们在Pubmed和Embase上对文献进行了系统性回顾,然后利用SSc患者的患病率、临床/病史/生物学特征以及抗TRIM21抗体检测方法(PROSPERO n° CRD42021223719)等数据进行了荟萃分析:在横断面研究中,抗TRIM21抗体的流行率为26%[95%CI:21;31]。抗中心粒抗体是与抗TRIM21抗体共存的最常见的SSc特异性自身抗体。抗TRIM21抗体患者多为女性(91% vs 77%,P = 0.006),更有可能伴有斯约格伦综合征(31% vs 11%,P 2:93% Phet):解释:抗TRIM21抗体经常与常见的SSc抗体同时存在,但却与较高的心肺并发症风险独立相关。因此,在评估罹患 PH 和 ILD 的风险时,应考虑到这些自身抗体的存在,并对患者的适当筛查和随访进行进一步研究。
{"title":"Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis","authors":"Marie-Elise Martel , Amélie Leurs , David Launay , Hélène Behal , Aurélien Chepy , Aurore Collet , Sébastien Sanges , Eric Hachulla , Sylvain Dubucquoi , Luc Dauchet , Vincent Sobanski","doi":"10.1016/j.autrev.2024.103536","DOIUrl":"10.1016/j.autrev.2024.103536","url":null,"abstract":"<div><h3>Objectives</h3><p>Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort.</p></div><div><h3>Methods</h3><p>Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719).</p></div><div><h3>Findings</h3><p>In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, <em>p</em> = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, <em>p</em> < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, <em>p</em> = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, <em>p</em> = 0.038) or nausea/vomiting (10% vs 3%, <em>p</em> = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I<sup>2</sup>: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]).</p></div><div><h3>Interpretation</h3><p>Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224000272/pdfft?md5=1498dd5cfeaa3d0df361ec3ed3b96f8d&pid=1-s2.0-S1568997224000272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-27DOI: 10.1016/j.autrev.2024.103535
Maurizio Bruschi , Andrea Angeletti , Marco Prunotto , Pier Luigi Meroni , Gian Marco Ghiggeri , for the Zeus consortium, Gabriella Moroni , Renato Alberto Sinico , Franco Franceschini , Micaela Fredi , Augusto Vaglio , Andrea Cavalli , Leonardo Scapozza , Jigar J. Patel , John C. Tan , Ken C. Lo , Lorenzo Cavagna , Andrea Petretto , Federico Pratesi , Paola Migliorini , Enrico Verrina
Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4.
Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as ‘second wave antibodies’ for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation.
These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.
{"title":"A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence","authors":"Maurizio Bruschi , Andrea Angeletti , Marco Prunotto , Pier Luigi Meroni , Gian Marco Ghiggeri , for the Zeus consortium, Gabriella Moroni , Renato Alberto Sinico , Franco Franceschini , Micaela Fredi , Augusto Vaglio , Andrea Cavalli , Leonardo Scapozza , Jigar J. Patel , John C. Tan , Ken C. Lo , Lorenzo Cavagna , Andrea Petretto , Federico Pratesi , Paola Migliorini , Enrico Verrina","doi":"10.1016/j.autrev.2024.103535","DOIUrl":"10.1016/j.autrev.2024.103535","url":null,"abstract":"<div><p>Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4.</p><p>Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as ‘second wave antibodies’ for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation.</p><p>These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-26DOI: 10.1016/j.autrev.2024.103534
Francesco Buonfiglio , Katharina A. Ponto , Norbert Pfeiffer , George J. Kahaly , Adrian Gericke
Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.
{"title":"Redox mechanisms in autoimmune thyroid eye disease","authors":"Francesco Buonfiglio , Katharina A. Ponto , Norbert Pfeiffer , George J. Kahaly , Adrian Gericke","doi":"10.1016/j.autrev.2024.103534","DOIUrl":"10.1016/j.autrev.2024.103534","url":null,"abstract":"<div><p>Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224000259/pdfft?md5=f294d9cea0af2aafe7a9385f34094adc&pid=1-s2.0-S1568997224000259-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-22DOI: 10.1016/j.autrev.2024.103533
Fabio Salvatore Macaluso , Flavio Caprioli , Laura Benedan , Cristina Bezzio , Roberto Caporali , Alberto Cauli , Maria Sole Chimenti , Francesco Ciccia , Salvatore D'Angelo , Massimo Claudio Fantini , Stefano Festa , Florenzo Iannone , Ennio Lubrano , Paolo Mariani , Claudio Papi , Giuseppe Provenzano , Daniela Pugliese , Antonio Rispo , Simone Saibeni , Carlo Salvarani , Roberto Gerli
Spondyloarthritis (SpA) is the most frequent extraintestinal manifestation in patients with inflammatory bowel diseases (IBD). When IBD and spondyloarthritis coexist, musculoskeletal and intestinal disease features should be considered when planning a therapeutic strategy. Treatment options for IBD and SpA have expanded enormously over the last few years, but randomized controlled trials with specific endpoints focused on SpA are not available in the IBD setting. To address this important clinical topic, the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and the Italian Society of Rheumatology (SIR) jointly planned to draw updated therapeutic recommendations for IBD-associated SpA using a pseudo-Delphi method. This document presents the official recommendations of IG-IBD and SIR on the management of IBD-associated SpA in the form of 34 statements and 4 therapeutic algorithms. It is intended to be a reference guide for gastroenterologists and rheumatologists dealing with IBD-associated SpA.
{"title":"The management of patients with inflammatory bowel disease-associated spondyloarthritis: Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and Italian Society of Rheumatology (SIR) recommendations based on a pseudo-Delphi consensus","authors":"Fabio Salvatore Macaluso , Flavio Caprioli , Laura Benedan , Cristina Bezzio , Roberto Caporali , Alberto Cauli , Maria Sole Chimenti , Francesco Ciccia , Salvatore D'Angelo , Massimo Claudio Fantini , Stefano Festa , Florenzo Iannone , Ennio Lubrano , Paolo Mariani , Claudio Papi , Giuseppe Provenzano , Daniela Pugliese , Antonio Rispo , Simone Saibeni , Carlo Salvarani , Roberto Gerli","doi":"10.1016/j.autrev.2024.103533","DOIUrl":"10.1016/j.autrev.2024.103533","url":null,"abstract":"<div><p>Spondyloarthritis (SpA) is the most frequent extraintestinal manifestation in patients with inflammatory bowel diseases (IBD). When IBD and spondyloarthritis coexist, musculoskeletal and intestinal disease features should be considered when planning a therapeutic strategy. Treatment options for IBD and SpA have expanded enormously over the last few years, but randomized controlled trials with specific endpoints focused on SpA are not available in the IBD setting. To address this important clinical topic, the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and the Italian Society of Rheumatology (SIR) jointly planned to draw updated therapeutic recommendations for IBD-associated SpA using a pseudo-Delphi method. This document presents the official recommendations of IG-IBD and SIR on the management of IBD-associated SpA in the form of 34 statements and 4 therapeutic algorithms. It is intended to be a reference guide for gastroenterologists and rheumatologists dealing with IBD-associated SpA.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224000247/pdfft?md5=95d2779faaa841c02b00711aa22154fa&pid=1-s2.0-S1568997224000247-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}