Common autoimmune diseases are relatively heterogeneous with both genetic and environmental factors influencing disease susceptibility and progression. As the populations in developed countries age, these chronic diseases will become an increasing burden in human suffering and health care costs. By contrast, rare immune diseases that are severe and develop early in childhood are frequently monogenic and fully penetrant, often with a Mendelian inheritance pattern. Although these may be incompatible with survival or cured by hematopoietic stem cell transplantation, we will argue that they constitute a rich source of genetic insights into immunological diseases. Here, we discuss five examples of well-studied Mendelian disease-causing genes and their known or predicted roles in conferring susceptibility to common, polygenic diseases of autoimmunity. Mendelian disease mutations, as experiments of nature, reveal human loci that are indispensable for immune regulation and, therefore, most promising as therapeutic targets.

中文翻译：

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确定自身免疫和免疫调节异常的遗传决定因素。

常见的自身免疫性疾病相对异质，具有影响疾病易感性和进展的遗传和环境因素。随着发达国家人口的老龄化，这些慢性疾病将成为人类苦难和医疗保健费用日益增加的负担。相比之下，严重且在儿童期早期发展的罕见免疫疾病通常是单基因的且具有充分的渗透性，通常具有孟德尔遗传模式。尽管这些可能与生存不相容或通过造血干细胞移植治愈，但我们将争辩说它们构成了免疫疾病遗传学见解的丰富来源。在这里，我们讨论了五个经过充分研究的孟德尔病原基因实例，以及它们在赋予常见，多基因自身免疫性疾病易感性中的已知作用或预测作用。