Department of Human Genetics, Genentech, Inc., South San Francisco, CA 94080, USA.
Curr Opin Immunol. 2012 Oct;24(5):530-7. doi: 10.1016/j.coi.2012.07.008. Epub 2012 Aug 10.
The discovery that type I interferon (IFN)-inducible genes were strongly upregulated in peripheral blood in SLE over a decade ago sparked interest in understanding the relationship between type I IFN and SLE. Genome-wide association studies provide strong genetic evidence that type I IFNs are important for SLE risk. Of 47 genetic variants associated with SLE, over half (27/47, 57%) can be linked to type I IFN production or signaling. The recent identification of single gene mutations for disorders that share features with SLE--Aicardi-Goutières syndrome, chilblain lupus, and spondyloenchondrodysplasia--provide additional support for the hypothesis that type I IFNs are central drivers of SLE pathogenesis. These insights provide significant focus for efforts to tackle SLE therapeutically.
十多年前，人们发现 1 型干扰素（IFN）诱导基因在系统性红斑狼疮（SLE）患者外周血中强烈上调，这激发了人们对理解 1 型 IFN 与 SLE 之间关系的兴趣。全基因组关联研究为 1 型 IFN 对 SLE 风险很重要提供了强有力的遗传证据。在与 SLE 相关的 47 种遗传变异中，超过一半（27/47，57%）可以与 1 型 IFN 的产生或信号转导相关联。最近，在具有与 SLE 相似特征的疾病（Aicardi-Goutières 综合征、冻疮样狼疮和脊椎骨骺发育不良）中发现了单个基因突变，这为 1 型 IFN 是 SLE 发病机制的核心驱动因素的假说提供了额外的支持。这些见解为 SLE 的治疗提供了重要的研究方向。
