补体旁路途径失调非典型溶血尿毒综合征的诊断和治疗

Diagnosis and Treatment of Atypical Hemolytic Uremic Syndrome Caused by Complement Dysregulation

补体旁路途径失调非典型溶血尿毒综合征(aHUS)是指因补体基因致病变异或抗补体因子H(CFH)抗体所致的溶血尿毒综合征。其诊断包括临床诊断和基因诊断,全基因组测序(WGS)结合转录组测序(RNAseq)相较于靶基因测序Panel或全外显子组测序(WES)可提高致病变异检出率。人抗C5单克隆抗体依库珠单抗(eculizumab)已被用作治疗补体旁路途径失调aHUS的一线疗法,由依库珠单抗设计的长效补体C5抑制剂雷夫利珠单抗(Ravulizumab)应用于aHUS儿童和成人,均能快速改善血液学和肾脏参数,安全性好。本文对补体旁路途径失调aHUS的临床表型、发病机制、诊断和治疗进行了综述,以期为该病提供更全面的诊断和治疗方案。

Atypical hemolytic uremic syndrome(aHUS)caused by complement dysregulation,complement-mediated aHUS,is defined as a hemolytic uremic syndrome caused by pathogenic variants in the complement genes,such as CFH,MCP,CFI,CFHR5,THBD,CFB and C3,or by anti-complement factor H(CFH)antibodies.Its diagnosis includes clinical diagnosis and genetic diagnosis.Compared with targeted gene sequencing panel or whole exome sequencing(WES),whole genome sequencing(WGS)combined with transcriptome sequencing(RNAseq)can increase the detection rate of pathogenic variants in the complement genes.Eculizumab has been recommended as first-line treatment for complement-mediated aHUS.Ravulizumab,a long-acting C5 inhibitor engineered from eculizumab,can rapidly improve hematological and kidney parameters with good safety in children and adults with complement-mediated aHUS.This article reviews the clinical phenotypes,pathogenesis,diagnosis and treatment of complement-mediated aHUS in order to provide a comprehensive diagnosis and treatment plan for the disease.