补体在镰状细胞病引起的急性胸综合征患者中被激活,是一个治疗靶点

IF 14.6 1区 医学 Q1 CELL BIOLOGY
Satheesh Chonat, Jayre A. Jones, Seema R. Patel, William M. Briones, Michelle L. Schoettler, Maya Maarouf, Lauren A. Jeffers, Olufolake Adisa, Fang Tan, Earl Fields, Morgan S. Sterling, Ryan P. Jajosky, Hans Verkerke, Sara H. Graciaa, Elisabetta M. Foppiani, Ross M. Fasano, Patricia E. Zerra, Yongzhi Qiu, Connie M. Arthur, Wilbur A. Lam, Solomon F. Ofori-Acquah, Michael Koval, Clinton H. Joiner, David R. Archer, Sean R. Stowell
{"title":"补体在镰状细胞病引起的急性胸综合征患者中被激活,是一个治疗靶点","authors":"Satheesh Chonat,&nbsp;Jayre A. Jones,&nbsp;Seema R. Patel,&nbsp;William M. Briones,&nbsp;Michelle L. Schoettler,&nbsp;Maya Maarouf,&nbsp;Lauren A. Jeffers,&nbsp;Olufolake Adisa,&nbsp;Fang Tan,&nbsp;Earl Fields,&nbsp;Morgan S. Sterling,&nbsp;Ryan P. Jajosky,&nbsp;Hans Verkerke,&nbsp;Sara H. Graciaa,&nbsp;Elisabetta M. Foppiani,&nbsp;Ross M. Fasano,&nbsp;Patricia E. Zerra,&nbsp;Yongzhi Qiu,&nbsp;Connie M. Arthur,&nbsp;Wilbur A. Lam,&nbsp;Solomon F. Ofori-Acquah,&nbsp;Michael Koval,&nbsp;Clinton H. Joiner,&nbsp;David R. Archer,&nbsp;Sean R. Stowell","doi":"10.1126/scitranslmed.adl4922","DOIUrl":null,"url":null,"abstract":"<div >Despite being the first genetic disease described, sickle cell disease (SCD) continues to result in severe complications. Of these complications, acute chest syndrome (ACS), a form of acute lung injury, leads all-cause mortality. However, the pathophysiology of ACS remains incompletely understood, resulting in patients with ACS receiving only supportive measures. Here, we found that ACS is accompanied by activation of the complement pathway, an evolutionarily ancient innate immune system responsible for eliminating microbes. Using a well-defined preclinical model of SCD, hemolysis, a precursor of ACS, not only induced ACS but also drove robust complement activation. Artificial activation of complement alone similarly induced ACS, whereas genetic removal or pharmacological inhibition of complement rendered SCD mice resistant to ACS even after induction of hemolysis. These results demonstrate that complement drives ACS, establishing a link between SCD and this ancient form of immunity that provides an opportunity for targeted treatment of this complication.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 807","pages":""},"PeriodicalIF":14.6000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target\",\"authors\":\"Satheesh Chonat,&nbsp;Jayre A. Jones,&nbsp;Seema R. Patel,&nbsp;William M. Briones,&nbsp;Michelle L. Schoettler,&nbsp;Maya Maarouf,&nbsp;Lauren A. Jeffers,&nbsp;Olufolake Adisa,&nbsp;Fang Tan,&nbsp;Earl Fields,&nbsp;Morgan S. Sterling,&nbsp;Ryan P. Jajosky,&nbsp;Hans Verkerke,&nbsp;Sara H. Graciaa,&nbsp;Elisabetta M. Foppiani,&nbsp;Ross M. Fasano,&nbsp;Patricia E. Zerra,&nbsp;Yongzhi Qiu,&nbsp;Connie M. Arthur,&nbsp;Wilbur A. Lam,&nbsp;Solomon F. Ofori-Acquah,&nbsp;Michael Koval,&nbsp;Clinton H. Joiner,&nbsp;David R. Archer,&nbsp;Sean R. Stowell\",\"doi\":\"10.1126/scitranslmed.adl4922\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >Despite being the first genetic disease described, sickle cell disease (SCD) continues to result in severe complications. Of these complications, acute chest syndrome (ACS), a form of acute lung injury, leads all-cause mortality. However, the pathophysiology of ACS remains incompletely understood, resulting in patients with ACS receiving only supportive measures. Here, we found that ACS is accompanied by activation of the complement pathway, an evolutionarily ancient innate immune system responsible for eliminating microbes. Using a well-defined preclinical model of SCD, hemolysis, a precursor of ACS, not only induced ACS but also drove robust complement activation. Artificial activation of complement alone similarly induced ACS, whereas genetic removal or pharmacological inhibition of complement rendered SCD mice resistant to ACS even after induction of hemolysis. These results demonstrate that complement drives ACS, establishing a link between SCD and this ancient form of immunity that provides an opportunity for targeted treatment of this complication.</div>\",\"PeriodicalId\":21580,\"journal\":{\"name\":\"Science Translational Medicine\",\"volume\":\"17 807\",\"pages\":\"\"},\"PeriodicalIF\":14.6000,\"publicationDate\":\"2025-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/scitranslmed.adl4922\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/scitranslmed.adl4922","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

尽管镰状细胞病(SCD)是第一个被描述的遗传性疾病,但它仍然导致严重的并发症。在这些并发症中,急性胸综合征(ACS)是一种急性肺损伤,导致全因死亡率。然而,ACS的病理生理学仍然不完全了解,导致ACS患者只接受支持措施。在这里,我们发现ACS伴随着补体途径的激活,补体途径是一种进化上古老的先天免疫系统,负责消除微生物。使用一个定义良好的SCD临床前模型,溶血(ACS的前体)不仅诱导ACS,而且还驱动强大的补体激活。补体单独的人工激活同样诱导ACS,而补体的遗传去除或药理抑制使SCD小鼠即使在诱导溶血后也对ACS产生抗性。这些结果表明,补体驱动ACS,建立了SCD和这种古老的免疫形式之间的联系,为靶向治疗这种并发症提供了机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target
Despite being the first genetic disease described, sickle cell disease (SCD) continues to result in severe complications. Of these complications, acute chest syndrome (ACS), a form of acute lung injury, leads all-cause mortality. However, the pathophysiology of ACS remains incompletely understood, resulting in patients with ACS receiving only supportive measures. Here, we found that ACS is accompanied by activation of the complement pathway, an evolutionarily ancient innate immune system responsible for eliminating microbes. Using a well-defined preclinical model of SCD, hemolysis, a precursor of ACS, not only induced ACS but also drove robust complement activation. Artificial activation of complement alone similarly induced ACS, whereas genetic removal or pharmacological inhibition of complement rendered SCD mice resistant to ACS even after induction of hemolysis. These results demonstrate that complement drives ACS, establishing a link between SCD and this ancient form of immunity that provides an opportunity for targeted treatment of this complication.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信