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浙江大学学报（医学版）
浙江大学学报（医学版）  2021, Vol. 50 Issue (4): 537-544    DOI: 10.3724/zdxbyxb-2021-0252
综述     
新生儿Fc受体基础研究和临床应用进展
胡茫莎1(),韦树丽1,周武源2,*(),王苹莉1,*()
1.浙江大学医学院附属第二医院呼吸内科，浙江 杭州 310009
2.浙江省科技信息研究院，浙江 杭州 310006
Research progress on neonatal Fc receptor and its application
HU Mangsha1(),WEI Shuli1,ZHOU Wuyuan2,*(),WANG Pingli1,*()
1. Department of Respiratory Medicine, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;
2. Zhejiang Academy of Science and Technology Information, Hangzhou 310006, China
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摘要：

新生儿Fc受体（FcRn）是免疫球蛋白G（IgG）和白蛋白的特异性受体，通过酸碱度依赖的方式与两者结合，使IgG和白蛋白免于被溶酶体降解而拥有较长的血浆半衰期。FcRn具有实现IgG和白蛋白的跨膜转运及促进抗原提呈的作用。在自身免疫病中，抗FcRn抗体可以通过竞争性结合FcRn，促进致病性IgG的降解；在传染性疾病中，通过增加治疗抗体与FcRn的亲和力，可以延长药物半衰期，而将病毒抗原与IgG的Fc片段结合可以引起黏膜的局部免疫反应，用于疾病防治；在癌症中，FcRn的配体白蛋白作为抗癌药物的载体，可以实现高效给药，而FcRn本身或许可以作为肿瘤患者预后的预测指标。本文综述了FcRn的功能、相关药物研发机制及其在自身免疫病、传染性疾病和癌症中的作用，以期为FcRn的药物研发和临床应用提供参考。
关键词： 新生儿Fc受体;  免疫球蛋白G;  白蛋白;  自身免疫病;  传染病;  癌症;  综述    
Abstract:

Neonatal Fc receptor (FcRn) is a specific receptor for immunoglobulin G (IgG) and albumin, which binds to them in a pH-dependent manner and prevents them from lysosomal degradation to keep a long plasma half-life. In addition, FcRn plays an important role in transmembrane transport of IgG and albumin and in antigen presentation. In autoimmune diseases, anti-FcRn antibody can promote the degradation of pathogenic IgG by competitive binding to FcRn. In infectious diseases, the half-life of drugs can be prolonged by increasing the affinity between therapeutic antibody and FcRn, while the combination of viral antigen and Fc fragment of IgG can cause local immune response of mucosa for disease prevention and treatment. In cancer, albumin as a carrier of anticancer drugs can achieve efficient drug delivery, and FcRn itself may be used as a predictor of the prognosis of cancer patients. This review details the functions of FcRn, highlights its role in autoimmune diseases, infectious diseases and cancer, as well as the mechanism of drug development based on FcRn, to provide a reference for the clinical application and drug development of FcRn.
Key words: Neonatal Fc receptor    Immunoglobulin G    Albumin    Autoimmune disease    Infectious disease    Cancer    Review
收稿日期: 2021-02-03 出版日期: 2021-11-01
CLC:  R392  
基金资助: 浙江省医药卫生科技计划（WKJ-ZJ-2122）
通讯作者: 周武源,王苹莉     E-mail: 22018330@zju.edu.cn;pingliwang@zju.edu.cn
作者简介: 胡茫莎，住院医师，主要从事呼吸病的诊断与治疗研究；E-mail：22018330@zju.edu.cn；https：//orcid.org/0000-0002-1600-7050
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引用本文:

胡茫莎,韦树丽,周武源,王苹莉. 新生儿Fc受体基础研究和临床应用进展[J]. 浙江大学学报（医学版）, 2021, 50(4): 537-544.

HU Mangsha,WEI Shuli,ZHOU Wuyuan,WANG Pingli. Research progress on neonatal Fc receptor and its application. J Zhejiang Univ (Med Sci), 2021, 50(4): 537-544.

链接本文:

http://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0252    或    http://www.zjujournals.com/med/CN/Y2021/V50/I4/537

图 1  新生儿Fc受体结构示意图虚线方框所选结构对应主要组织相容性复合体Ⅰ类分子的α1-α2所形成的抗原提呈槽，在Fc受体中，该处为封闭状态.
图 2  新生儿Fc受体的功能示意图A：细胞通过胞吞作用摄取细胞外的免疫球蛋白G（IgG）抗体、白蛋白及其他蛋白质，形成的囊泡与含有Fc受体的早期内体融合后，IgG及白蛋白可以通过与细胞膜上的Fc受体结合而避免被溶酶体降解；B：在肠道、呼吸道、胎盘等部位的Fc受体可以进一步将与之结合的IgG和白蛋白转运至细胞基底侧，实现跨膜转运；C：IgG-抗原复合物多聚体与抗原提呈细胞上的Fcγ受体结合后被胞吞形成囊泡，当与含有Fc受体的早期内体融合后，随着所处环境酸碱度的下降， IgG-抗原复合物多聚体与Fcγ受体分离而与Fc受体结合，并被转运至溶酶体进一步分解成抗原肽，最后由主要组织相容性复合体（MHC）Ⅰ类分子及MHC Ⅱ类分子提呈至细胞表面.
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