Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond

伊库利珠单抗 补体系统 阵发性夜间血红蛋白尿 免疫学 非典型溶血尿毒综合征 医学 补体成分5 凝集素途径 补语(音乐) 替代补体途径 免疫系统 生物 遗传学 基因 表型 互补
作者
Eleni Gavriilaki,Régis Peffault de Latour,Antonio M. Risitano
出处
期刊:Blood [Elsevier BV]
卷期号:139 (25): 3571-3582 被引量:26
标识
DOI:10.1182/blood.2021012860
摘要

Complement is an elaborate system of innate immunity. Genetic variants and autoantibodies leading to excessive complement activation are implicated in a variety of human diseases. Among them, the hematologic disease paroxysmal nocturnal hemoglobinuria (PNH) remains the prototypic model of complement activation and inhibition. Eculizumab, the first-in-class complement inhibitor, was approved for PNH in 2007. Addressing some of the unmet needs, a long-acting C5 inhibitor, ravulizumab, and a C3 inhibitor, pegcetacoplan, have also now been approved for PNH. Novel agents, such as factor B and factor D inhibitors, are under study, with very promising results. In this era of several approved targeted complement therapeutics, selection of the proper drug must be based on a personalized approach. Beyond PNH, complement inhibition has also shown efficacy and safety in cold agglutinin disease, primarily with the C1s inhibitor of the classical complement pathway sutimlimab, as well as with pegcetacoplan. Furthermore, C5 inhibition with eculizumab and ravulizumab, as well as inhibition of the lectin pathway with narsoplimab, is being investigated in transplantation-associated thrombotic microangiopathy. With this revolution of next-generation complement therapeutics, additional hematologic entities, such as delayed hemolytic transfusion reaction or immune thrombocytopenia, might also benefit from complement inhibitors. Therefore, this review aims to describe state-of-the-art knowledge of targeting complement in hematologic diseases, focusing on (1) complement biology for the clinician, (2) complement activation and therapeutic inhibition in prototypic complement-mediated hematologic diseases, (3) hematologic entities under investigation for complement inhibition, and (4) other complement-related disorders of potential interest to hematologists.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
浅浅完成签到,获得积分10
3秒前
量子星尘发布了新的文献求助10
8秒前
帅气的藏鸟完成签到,获得积分10
12秒前
加油完成签到 ,获得积分10
13秒前
健康的宛菡完成签到 ,获得积分10
14秒前
橙果果发布了新的文献求助20
14秒前
晚晚完成签到,获得积分10
15秒前
15秒前
听闻韬声依旧完成签到 ,获得积分10
15秒前
ZHZ完成签到,获得积分10
16秒前
啊哈啊哈额完成签到,获得积分10
16秒前
yyy完成签到,获得积分10
17秒前
17秒前
xiaoputaor完成签到 ,获得积分10
18秒前
Camus发布了新的文献求助10
18秒前
paper reader完成签到,获得积分10
18秒前
19秒前
八八九九九1完成签到,获得积分10
20秒前
tigger完成签到 ,获得积分10
21秒前
23秒前
25秒前
优雅的千雁完成签到,获得积分10
27秒前
2316690509完成签到 ,获得积分10
27秒前
没用的三轮完成签到,获得积分10
27秒前
fancy完成签到 ,获得积分10
27秒前
mayberichard完成签到,获得积分10
31秒前
LINDENG2004完成签到 ,获得积分10
37秒前
wz完成签到,获得积分10
38秒前
简奥斯汀完成签到 ,获得积分10
45秒前
五本笔记完成签到 ,获得积分10
45秒前
48秒前
花花发布了新的文献求助20
48秒前
asd113发布了新的文献求助10
52秒前
美满的小蘑菇完成签到 ,获得积分10
52秒前
自然白安完成签到 ,获得积分10
58秒前
量子星尘发布了新的文献求助10
1分钟前
等待小鸽子完成签到 ,获得积分10
1分钟前
龙虾发票完成签到,获得积分10
1分钟前
小康学弟完成签到 ,获得积分10
1分钟前
了0完成签到 ,获得积分10
1分钟前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038066
求助须知:如何正确求助?哪些是违规求助? 3575779
关于积分的说明 11373801
捐赠科研通 3305584
什么是DOI,文献DOI怎么找? 1819239
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022