生物制剂在儿童肾病综合征中的应用  

Application of biological agents in children with primary nephrotic syndrome

作　　者：于力 YU Li(Department of Pediatrics,Guangzhou First People’s Hospital,the Second Affiliated Hospital of South China University of Technology,Guangzhou 510180,China)

机构地区：[1]广州市第一人民医院,华南理工大学附属第二医院儿科,广州510180

出　　处：《实用医学杂志》2021年第15期1911-1915,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81670652,81273205)。

摘　　要：儿童原发性肾病综合征(primary nephroticsyndrome,PNS)是常见的肾小球疾病,其发病机制与B淋巴细胞功能异常表达密切相关。随着生物制剂应用,以CD20为靶点的抗体药物,分为三代:(1)第一代:利妥昔单抗(Rituximab,RTX)作为一种人鼠嵌合型抗CD20单克隆抗体,主要耗竭B淋巴细胞,通过有效阻止B细胞增殖和分化,减少细胞因子分泌。临床上RTX使长期应用激素和免疫抑制剂的PNS患儿减少使用剂量,甚至停用,减少PNS复发,副作用较少。(2)第二代:奥法木单抗(Ofatumumab)作为一种人源化靶点CD20的单克隆抗体,除RTX以外应用于肾脏领域最有前景的生物制剂,与RTX识别的表位不同,降低其免疫原性。因其高剂量应用时的不良反应更少,似乎较RTX更为优越。临床用于RTX耐药或过敏的PNS患儿。(3)第三代:奥比妥珠单抗(Obinutuzumab)作为首个糖基化的Ⅱ型抗CD20单克隆抗体,其抗体的Fc片段经过了糖基化修饰,提高了抗体的特异性及与抗原结合的亲和力,主要用于RTX耐药或过敏的膜性肾病患者。Primary Nephrotic Syndrome(PNS)in children is a common glomerular disease whose pathogenesis is closely related to the abnormal expression of B lymphocyte function.With the application of biological agents,antibody drugs targeting CD20 are divided into three generations.(1)First generation:Rituximab(RTX)as a human⁃mouse chimeric anti⁃CD20 monoclonal antibody,mainly depletes B lymphocytes and reduces cytokine secretion by effectively blocking B cell proliferation and differentiation.Clinically RTX enables children with PNS on long⁃term hormone and immunosuppressant use to reduce the dose or even stop using it,reducing PNS relapse with fewer side effects.(2)Second generation:Ofatumumab,as a monoclonal antibody to the humanised target CD20,is the most promising biologic agent for renal applications other than RTX,recognising a different epitope to RTX and reducing its immunogenicity.It appears to be superior to RTX due to fewer adverse effects when applied at high doses.It is used clinically in PNS with RTX⁃resistant or allergic.(3)Third generation:Obinutuzumab,the first glycosylated type II anti⁃CD20 monoclonal antibody,has a glycosylated Fc fragment that improves the specificity of the antibody and its affinity for antigen binding.Biological agentsare expected to be the first⁃line drugs for the treatment of nephrotic syndrome in children.

关 键 词：生物制剂 肾病综合征 治疗 临床 儿童 

分 类 号：R725[医药卫生—儿科]