Abstract：
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by its large heterogeneity in terms of clinical presentation and severity. The pathophysiology of SLE involves an aberrant autoimmune response against various tissues, an excess of apoptotic bodies, and an overproduction of type-I interferon. The genetic contribution to the disease is supported by studies of monozygotic twins, familial clustering, and genome-wide association studies (GWAS) that have identified numerous risk loci. In the early 70s, complement deficiencies led to the description of familial forms of SLE caused by a single gene defect. High-throughput sequencing has recently identified an increasing number of monogenic defects associated with lupus, shaping the concept of monogenic lupus and enhancing our insights into immune tolerance mechanisms. Monogenic lupus (moSLE) should be suspected in patients with either early-onset lupus or syndromic lupus, in male, or in familial cases of lupus. This review discusses the genetic basis of monogenic SLE and proposes its classification based on disrupted pathways. These pathways include defects in the clearance of apoptotic cells or immune complexes, interferonopathies, JAK-STATopathies, TLRopathies, and T and B cell dysregulations.
摘要：
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其临床表现和严重程度具有很大的异质性。SLE的病理生理学涉及针对各种组织的异常自身免疫反应,过量的凋亡体，和过量生产的I型干扰素。对这种疾病的遗传贡献得到了单卵双胞胎研究的支持，家族聚类，和全基因组关联研究(GWAS)已经确定了许多风险基因座。在70年代初，补体缺乏导致描述由单个基因缺陷引起的家族性SLE。高通量测序最近发现越来越多的与狼疮相关的单基因缺陷，塑造单基因狼疮的概念，增强我们对免疫耐受机制的认识。早发性狼疮或综合征性狼疮患者应怀疑单基因狼疮（MOSLE）。在男性中，或家族性狼疮病例。这篇综述讨论了单基因SLE的遗传基础，并提出了基于破坏途径的分类。这些途径包括凋亡细胞或免疫复合物的清除缺陷，干扰素病,JAK状态,TLRopathies,以及T细胞和B细胞失调。
