Severe infectious diseases of childhood as monogenic inborn errors of immunity
Severe infectious diseases of childhood as monogenic inborn errors of immunity
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DOI：
10.1073/pnas.1521651112
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发表时间：
2015-12-22
影响因子：
11.1
通讯作者：
Casanova, Jean-Laurent
中科院分区：
文献类型：
--
作者：
Casanova, Jean-Laurent
本文回顾了世纪后半叶以来人类传染病遗传学领域的发展。特别是，它强调和解释的重要性，最近描述的单基因先天性免疫缺陷的潜在阻力或敏感性，以特定的感染。遗传理论的单基因成分为原发感染期间严重传染病的发生提供了合理的解释。在过去的20年里，越来越多的威胁生命的传染病袭击了健康的儿童，青少年，甚至年轻的成年人，这归因于单基因先天性免疫缺陷。这些研究受到植物和动物感染方面开创性但被忽视的发现的启发。传染病通常表现为散发性特征，因为人类基因型通常显示不完全的等位基因（大多数遗传易感个体保持健康）和可变的表达性（不同的感染可以在同一基因座上等位）。曾经被认为是典型的环境疾病的儿童传染病，实际上可能是人类最受基因决定的疾病之一。这个新生的、可检验的概念具有有趣的医学和生物学意义。
This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.