Abstract:

As a group of monogenic inherited disorders of immune function，primary immunodeficiency diseases usually have  specific pathogenesis and unique therapeutic targets. In the past ten years，in the newly discovered PIDs，a considerable part of the gain of function mutations（GOF），often manifested as autoimmune and inflammation. Small molecule inhibitors or biological macromolecules in the activated phosphoinositide 3-kinase syndrome（APDS），LPS-responsive and beige-like anchor protein deficiency（LRBA），Cytotoxic lymphocyte antigen 4 haploinsufficiency and STAT1 GOF mutation have achieved outstanding curative effect. The above treatment strategy based on the precise target indicates that PID as a typical indication, will likely bring a breakthrough in the next few years in precision medicine.

Key words: primary immunodeficiency disease, loss of function, gain of function, precision medicine

摘要：

作为一组单基因遗传的免疫功能缺陷性疾病，原发性免疫缺陷病（PID）通常具有明确的致病机制和特异的干预治疗靶点。近10年来新发现的PID病种中，相当部分具有功能获得性突变（GOF），临床上常表现为自身免疫和炎症反应。小分子抑制剂或生物大分子在激活磷脂酰肌醇-3激酶δ综合征、LPS反应性米色锚样蛋白缺陷、细胞毒性淋巴细胞抗原4单倍剂量不足和STAT1 基因GOF等几种疾病中均已取得显著治疗效果。上述基于精准靶点的治疗策略体现了PID作为典型适应证，今后数年将可能为精准医学带来突破性进展。

关键词: 原发性免疫缺陷病, 功能缺失性突变, 功能获得性突变, 精准医学