{"title":"轴性脊柱关节炎发病机制中的 CARD9。","authors":"","doi":"10.1016/j.berh.2024.101964","DOIUrl":null,"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":4.5000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CARD9 in the pathogenesis of axial spondyloarthritis\",\"authors\":\"\",\"doi\":\"10.1016/j.berh.2024.101964\",\"DOIUrl\":null,\"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\":4.5000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Best Practice & Research in Clinical Rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1521694224000354\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Best Practice & Research in Clinical Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521694224000354","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
轴性脊柱关节炎(axSpA)长期以来一直被归类为一种自身免疫性疾病,是由于免疫系统区分自身和外来疾病的能力下降,导致自身反应性 T 细胞引起的。HLA-B27 的强遗传关联支持了 T 细胞的这种作用。最近,遗传学和临床研究表明,环境在诱发轴索硬化症中起着重要作用,包括微生物和先天性免疫反应的重要作用。例如,与先天性免疫相关的基因突变(包括抗真菌信号分子 Caspase recruitment domain-containing protein 9 (CARD9))与 axSpA 易感性有关。因此,目前的观点将 axSpA 归类为由自身免疫和自身炎症机制引起的 "混合模式病症"。本综述旨在传达以下信息
CARD9 in the pathogenesis of axial spondyloarthritis
Axial spondyloarthritis (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 T cells. The strong genetic association of HLA-B27 supports this role for T cells. 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 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.
The goal of this review is to convey:
•
Genetic/environmental mediating factors in axSpA
•
Known roles for CARD9 in anti-fungal immunity versus sterile inflammation
•
Previously characterized neutrophil-intrinsic roles for CARD9
•
Studies supporting a role for CARD9S12N mutation in promoting axSpA
期刊介绍:
Evidence-based updates of best clinical practice across the spectrum of musculoskeletal conditions.
Best Practice & Research: Clinical Rheumatology keeps the clinician or trainee informed of the latest developments and current recommended practice in the rapidly advancing fields of musculoskeletal conditions and science.
The series provides a continuous update of current clinical practice. It is a topical serial publication that covers the spectrum of musculoskeletal conditions in a 4-year cycle. Each topic-based issue contains around 200 pages of practical, evidence-based review articles, which integrate the results from the latest original research with current clinical practice and thinking to provide a continuous update.
Each issue follows a problem-orientated approach that focuses on the key questions to be addressed, clearly defining what is known and not known. The review articles seek to address the clinical issues of diagnosis, treatment and patient management. Management is described in practical terms so that it can be applied to the individual patient. The serial is aimed at the physician in both practice and training.