Department of Pediatrics, Division of Rheumatology/Immunology, Washington University School of Medicine in St. Louis, Missouri 63110, USA; email:
Annu Rev Immunol. 2021 Apr 26;39:227-249. doi: 10.1146/annurev-immunol-093019-124513. Epub 2021 Feb 3.
Primary immunodeficiency diseases (PIDs) are a rapidly growing, heterogeneous group of genetically determined diseases characterized by defects in the immune system. While individually rare, collectively PIDs affect between 1/1,000 and 1/5,000 people worldwide. The clinical manifestations of PIDs vary from susceptibility to infections to autoimmunity and bone marrow failure. Our understanding of the human immune response has advanced by investigation and discovery of genetic mechanisms of PIDs. Studying patients with isolated genetic variants in proteins that participate in complex signaling pathways has led to an enhanced understanding of host response to infection, and mechanisms of autoimmunity and autoinflammation. Identifying genetic mechanisms of PIDs not only furthers immunological knowledge but also benefits patients by dictating targeted therapies or hematopoietic stem cell transplantation. Here, we highlight several of these areas in the field of primary immunodeficiency, with a focus on the most recent advances.
原发性免疫缺陷病（PIDs）是一组快速增长的、异质性的遗传性疾病，其特征为免疫系统缺陷。虽然它们各自较为罕见，但总体而言，PIDs 影响全球每 1000 至 5000 人中的 1 人。PIDs 的临床表现从易感染到自身免疫和骨髓衰竭不等。通过对 PIDs 的遗传机制的研究和发现，我们对人类免疫反应的理解得到了提高。对参与复杂信号通路的蛋白质中孤立遗传变异的研究，使人们对宿主对感染的反应以及自身免疫和自身炎症的机制有了更深入的了解。确定 PIDs 的遗传机制不仅有助于免疫学知识的发展，还通过决定靶向治疗或造血干细胞移植使患者受益。在这里，我们重点介绍原发性免疫缺陷领域的几个此类领域，并关注最新进展。
