{"title":"Dendritic cells and antigen-specific immunotherapy in autoimmune rheumatic diseases","authors":"","doi":"10.1016/j.berh.2024.101940","DOIUrl":"10.1016/j.berh.2024.101940","url":null,"abstract":"<div><p>Dendritic cells (DCs) are professional antigen-presenting cells and trigger downstream immune responses to antigen while integrating cellular pathogen and damage-associated molecular pattern (PAMP and DAMP) or immunomodulatory signals. In healthy individuals, resting and tolerogenic DCs draining skin and intestine facilitate expansion of regulatory T cells (Treg) to maintain peripheral antigen-specific immune tolerance. In patients with rheumatic diseases, however, DCs activated by PAMPs and DAMPs expand self-reactive effector T cells, including follicular helper T cells that promote the expansion of activated autoreactive B cells, chronic inflammation and end-organ damage. With the development of cellular and nanoparticle (NP)-based self-antigen-specific immunotherapies we here consider the new opportunities and the challenges for restoring immunoregulation in the treatment and prevention of autoimmune inflammatory rheumatic conditions through DCs.</p></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101940"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521694224000111/pdfft?md5=bf169639c49fdd2ca495145dff4e0c7d&pid=1-s2.0-S1521694224000111-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential therapeutic targets of fibrosis in inflammatory rheumatic diseases","authors":"","doi":"10.1016/j.berh.2024.101945","DOIUrl":"10.1016/j.berh.2024.101945","url":null,"abstract":"<div><p><span>Fibrosis<span> is commonly associated with chronic rheumatic diseases, and causes substantial morbidity and mortality. Treatment of fibrosis is extremely challenging but is badly needed, as approved antifibrotic therapies fibrosis do not halt its progression, which will be discussed with a focus on </span></span>pulmonary fibrosis<span>. Findings from recent studies indicate several therapeutic targets for treating fibrosis. Interleukin-11 is emerging as a fibrogenic<span> cytokine whose activity can be blocked with neutralizing monoclonal antibodies. Fibroblast activation protein (FAP) is highly expressed by activated fibroblasts in inflammatory and fibrotic tissues. Targeting FAP with different modalities has been extensively explored as adjunct treatment for cancer, which can also apply to treating fibrosis in rheumatic diseases.</span></span></p></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101945"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867478","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":"Granzyme K+ CD8 T cells in autoimmunity","authors":"","doi":"10.1016/j.berh.2024.101930","DOIUrl":"10.1016/j.berh.2024.101930","url":null,"abstract":"<div><p>CD8 T cells expressing granzyme K are enriched in synovial tissue from patients with rheumatoid arthritis and in tissues affected by several other autoimmune diseases. The roles these cells play in autoimmune disease is under active investigation, and several recent studies have begun to shed light on this question. Putting this cell type into functional perspective is especially important given their enrichment at the sites of disease. This review summarizes available evidence for the presence of CD8 T cells and other granzyme K-expressing cells in tissues in autoimmune diseases and discusses the effects these cells may have on the pathogenesis of autoimmune conditions.</p></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101930"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658949","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":"CARD9 in the pathogenesis of axial spondyloarthritis","authors":"","doi":"10.1016/j.berh.2024.101964","DOIUrl":"10.1016/j.berh.2024.101964","url":null,"abstract":"<div><p>Axial spondyloarthritis<span><span><span> (axSpA) has been long classified as an autoimmune disease caused by a breakdown in the ability of the immune system to delineate self from foreign, resulting in self-reactive </span>T cells. The strong </span>genetic<span><span> association of HLA-B27 supports this role for T cells<span>. More recently, genetic and clinical studies indicate a prominent role of the environment in triggering axSpA, including an important role for microbes and the innate immune response. As an example, mutations in genes associated with innate immunity, including the anti-fungal signaling molecule </span></span>Caspase recruitment domain-containing protein 9 (CARD9), have been linked to axSpA susceptibility. Thus, current thought classifies axSpA as a “mixed pattern condition” caused by both autoimmune and autoinflammatory mechanisms.</span></span></p><p>The goal of this review is to convey:</p><ul><li><span>•</span><span><p>Genetic/environmental mediating factors in axSpA</p></span></li><li><span>•</span><span><p>Known roles for CARD9 in anti-fungal immunity versus sterile inflammation</p></span></li><li><span>•</span><span><p>Previously characterized neutrophil-intrinsic roles for CARD9</p></span></li><li><span>•</span><span><p>Studies supporting a role for CARD9<sup>S12N</sup> mutation in promoting axSpA</p></span></li></ul></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101964"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428220","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":"Immunopathology of inflammatory rheumatic diseases","authors":"Xiaofei Shi, Cong-Qiu Chu","doi":"10.1016/j.berh.2024.101980","DOIUrl":"10.1016/j.berh.2024.101980","url":null,"abstract":"","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101980"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789823","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":"Exploring the role of gut microbes in spondyloarthritis: Implications for pathogenesis and therapeutic strategies","authors":"","doi":"10.1016/j.berh.2024.101961","DOIUrl":"10.1016/j.berh.2024.101961","url":null,"abstract":"<div><p><span><span>The gut microbiota<span> plays a pivotal role in regulating host immunity, and dysregulation of this interaction is implicated in autoimmune and inflammatory diseases, including </span></span>spondyloarthritis<span> (SpA). This review explores microbial dysbiosis<span> and altered metabolic function observed in various forms of SpA, such as ankylosing spondylitis<span> (AS), psoriatic arthritis (PsA), acute anterior </span></span></span></span>uveitis<span><span> (AAU), and SpA-associated gut inflammation. Studies on animal models and clinical samples highlight the association between gut microbial dysbiosis, metabolic perturbations and </span>immune dysregulation<span> in SpA pathogenesis. These studies have received impetus through next-generation sequencing methods, which have enabled the characterization of gut microbial composition and function, and host gene expression. Microbial/metabolomic studies have revealed potential biomarkers and therapeutic targets, such as short-chain fatty acids, and tryptophan metabolites, offering insights into disease mechanisms and treatment approaches. Further studies on microbial function and its modulation of the immune response have uncovered molecular mechanisms underlying various SpA. Understanding the complex interplay between microbial community structure and function holds promise for improved diagnosis and management of SpA and other autoimmune disorders.</span></span></p></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101961"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293917","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 cell activation and autoantibody production in autoimmune diseases","authors":"","doi":"10.1016/j.berh.2024.101936","DOIUrl":"10.1016/j.berh.2024.101936","url":null,"abstract":"<div><p>B cells are central players in the immune system, responsible for producing antibodies and modulating immune responses. This review explores the intricate relationship between aberrant B cell activation and the development of autoimmune diseases, emphasizing the essential role of B cells in these conditions. We also summarize B cell receptor signaling and Toll-like receptor signaling in B cell activation, as well as their association with autoimmune diseases, shedding light on the molecular mechanisms behind these associations. Additionally, we explore the clinical observations involving B cell activation and their significance in autoimmune disease management. Various clinical studies related to B cell-targeted therapies are also discussed, offering insights into potential avenues for improving treatment strategies. Overall, this review serves as a resource for researchers and clinicians in the field of immunology and autoimmune diseases, providing a general view of B cell signaling and its role in autoimmunity.</p></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101936"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703971","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":"TNFR2 signalling in inflammatory diseases","authors":"","doi":"10.1016/j.berh.2024.101941","DOIUrl":"10.1016/j.berh.2024.101941","url":null,"abstract":"<div><p><span>TNF<span> signals via two receptors, TNFR1 and TNFR2, which play contrasting roles in immunity. Most of the pro-inflammatory effects of TNF are mediated by TNFR1, whereas TNFR2 is mainly involved in immune </span></span>homeostasis<span><span> and tissue healing, but also contributes to tumour progression. However, all currently available anti-TNF biologics inhibit signalling via both receptors and there is increasing interest in the development of selective inhibitors; TNFR1 inhibitors for autoimmune disease and TNFR2 inhibitors for cancer. It is hypothesised that selective inhibition of TNFR1 in autoimmune disease would alleviate inflammation and promote homeostasis<span> by allowing TNFR2 signalling to proceed unimpeded. Validation of this concept would pave the way for the development and testing of TNF specific antagonists. Another therapeutic approach being explored is the use of TNFR2 specific </span></span>agonists, which could be administered alone or in combination with a TNFR1 antagonist.</span></p></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101941"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307726","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":"Biology of HLA class I associated inflammatory diseases","authors":"Ali Bordbar , Olivier Manches , Johannes Nowatzky","doi":"10.1016/j.berh.2024.101977","DOIUrl":"10.1016/j.berh.2024.101977","url":null,"abstract":"<div><p>Human leukocyte antigen (HLA) class I association is a well-established feature of common and uncommon inflammatory diseases, but it is unknown whether it impacts the pathogenesis of these disorders. The “arthritogenic peptide” hypothesis proposed initially for HLA-B27-associated ankylosing spondylitis (AS) seems the most intuitive to serve as a model for other HLA class I-associated diseases, but evidence supporting it has been scarce. Recent technological advances and the discovery of epistatic relationships between disease-associated HLA class I and endoplasmic reticulum aminopeptidase (ERAP) coding variants have led to the generation of new data and conceptual approaches to the problem requiring its re-examination. Continued success in these endeavors holds promise to resolve a Gordian Knot in human immunobiology. It may ultimately benefit patients by enabling the development of new therapies and precision tools for assessing disease risk and predicting treatment responses.</p></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 2","pages":"Article 101977"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861572","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":"Response to kollas. Letter to the editor, “problems with opioids beyond misuse”","authors":"","doi":"10.1016/j.berh.2024.101946","DOIUrl":"10.1016/j.berh.2024.101946","url":null,"abstract":"","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"38 1","pages":"Article 101946"},"PeriodicalIF":4.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873571","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}