免疫出生错误基于发病机制的精准治疗

舒洲; 毛华伟

doi:10.12376/j.issn.2097-0501.2022.03.004

免疫出生错误基于发病机制的精准治疗

doi: 10.12376/j.issn.2097-0501.2022.03.004

舒洲¹,
毛华伟^{1, 2, ,}

1.
国家儿童医学中心首都医科大学附属北京儿童医院免疫科北京 100045
2.
国家儿童医学中心首都医科大学附属北京儿童医院儿科重大疾病研究教育部重点实验室，北京 100045

基金项目:

国家自然科学基金面上项目 81971547

北京市教育委员会科学研究计划项目 KZ202210025030

详细信息

通信作者:
毛华伟，E-mail：maohwei@qq.com

中图分类号: R725.9
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- 被引次数: 0
出版历程
- 收稿日期: 2022-06-09
- 录用日期: 2022-06-24
- 网络出版日期: 2022-09-06

Pathogenesis based Precision Therapy for Inborn Errors of Immunity

SHU Zhou¹,
MAO Huawei^{1, 2
, ,}

1.
Department of Immunology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
2.
Key Laboratory of Major Diseases in Children of Ministry of Education, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China

Funding:

National Natural Science Foundation of China 81971547

Beijing Municipal Education Commission KZ202210025030

More Information

Corresponding author: MAO Huawei, E-mail: maohwei@qq.com

摘要

摘要: 精准医学是通过分析疾病发病机制寻找特异生物学标志物，并进行靶向治疗的学科。免疫出生错误是一类单基因突变导致的疾病，是研究免疫学机制的适宜人体模型。近年来随着科技日新月异，人类对免疫出生错误的临床表现型与基因型、基因型与特定靶点的认识越来越清楚，因此，为临床医务人员按照精准医学的原则诊断和治疗此类疾病提供了机遇。目前，针对免疫出生错误的精准治疗已有很多成功的范例，具有治疗疾病本质的优点。本文着重阐述了几类免疫出生错误病的精准治疗。
- 免疫出生错误 /
- 发病机制 /
- 精准治疗
Abstract: Precision medicine aims at using target therapy on specific diseases by studying the pathogenesis and finding biomarkers. Inborn errors of immunity (IEI) are caused by single gene mutations, providing the perfect human models to study immunology. The technology rapidly developes recently, so scientists have a deeper understandings of the phenotypes, genotypes, and the biological targets, so that doctors are able to use precision medicine on IEIs with many successful cases. The precision medicine have advantages in the treatment of pathogenesis of diseases. This article summarizes successful cases of using precision medicine for IEI recently.
- inborn errors of immunity /
- pathogenesis /
- precision therapy
注释:

作者贡献：舒洲负责撰写和修订稿件，翻译及校对；毛华伟负责确定主题，指导稿件撰写。

利益冲突：所有作者均声明不存在利益冲突。

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表 1 免疫出生错误药物精准治疗

Table 1. Precise therapies used in the treatment of inborn errors of immunity

药物	靶点	分子结构	适应证	超适应证用药
西罗莫司	mTOR	大环内酯复合物	肾移植排异淋巴管平滑肌瘤	NLCR4-GOF POMP缺陷 CTLA4单倍剂量不足 APDS
阿巴西普	B7-1 (CD80), B7-2 (CD86)	CTLA4 IgG融合蛋白	RA JIA	CTLA4单倍剂量不足 LRBA缺陷
贝拉西普	B7-1 (CD80), B7-2 (CD86)	CTLA4融合蛋白		CTLA4单倍剂量不足
阿那白滞素	IL-1R	重组人 IL-1R拮抗剂	RA JIA	CAPS
卡那单抗	IL-1β	抗人IL-1 IgG1 mAb	CAPS FCAS MWS	DIRA
列洛西普	IL-1β	双特异性的人源IgG1 Fc抗体	CAPS FCAS MWS	DIRA
托珠单抗	IL-6R	重组人源IgG1κ mAb	RA JIA	STAT3-GOF
依那西普	TNF-α	融合蛋白	RA JIA 银屑病关节炎斑片银屑病	SAVI CANDLE综合征 POMP缺陷 PAPA综合征 Blau综合征
英夫利昔单抗	TNF-α	嵌合mAb	克罗恩病 UC RA AS 银屑病关节炎斑片银屑病	SAVI CANDLE综合征 POMP缺陷 PAPA综合征 Blau综合征
阿达木单抗	TNF-α	人源mAb	RA JIA 银屑病关节炎斑片银屑病克罗恩病	SAVI CANDLE综合征 POMP缺陷 PAPA综合征 Blau综合征
芦可替尼	JAK1，JAK2	小分子抑制剂	骨髓纤维化红细胞增生症	STAT3-GOF STAT1-GOF CANDLE综合征
托法替布	JAK1，JAK3	小分子抑制剂	RA JIA	STAT3-GOF STAT1-GOF CANDLE综合征
巴瑞替尼	JAK1，JAK2	小分子抑制剂	RA	STAT1-GOF CANDLE综合征
干扰素单抗	抗体IFN-γ	人源化mAb	NA	HLH
他德白介素α	IL-18结合蛋白	重组人白介素IL-18结合蛋白	NA	NLCR4-GOF
优特克单抗	IL-12，IL-23 P40亚基	IgG1κ mAb	银屑病	LAD CGD肠炎
Leniolisib	PI3Kδ	小分子抑制剂	NA	APDS
mTOR：雷帕霉素靶蛋白；NLCR4-GOF：NLCR4增功能突变；CTLA4：细胞毒性T淋巴细胞相关抗原-4；APDS：PI3Kδ过度活化综合征；B7：B7家族分子成员；RA：类风湿关节炎；JIA：幼年特发性关节炎；IL-1R：白介素1受体；CAPS：冷炎素相关周期性综合征；FCAS：家族性寒冷型自身炎症综合征；MWS：Muckle-Wells综合征；DIRA：IL-1受体拮抗剂缺陷；IL-6R：白介素6受体；STAT-GOF：STAT增功能突变；SAVI：婴儿起病的STING相关血管病；CANDLE：非典型慢性中性粒细胞与脂肪代谢障碍性皮肤病和高体温综合征；PAPA：化脓性关节炎、坏疽性脓皮病和痤疮；UC：溃疡性结肠炎；AS：强直性脊柱炎；JAK：酪氨酸蛋白激酶；NA：无应用；HLH：家族性噬血细胞综合征；LAD：白细胞粘附分子缺陷；CGD：慢性肉芽肿病；PI3Kδ：磷脂酰激酶δ

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