Abstract：
Monogenic lupus, a distinctive variant of systemic lupus erythematosus (SLE), is characterized by early onset, family-centric clustering, and heightened disease severity. So far, over thirty genetic variations have been identified as single-gene etiology of SLE and lupus-like phenotypes. The critical role of these gene mutations in disrupting various immune pathways is increasingly recognized. In particular, single gene mutation-driven dysfunction within the innate immunity, notably deficiencies in the complement system, impedes the degradation of free nucleic acid and immune complexes, thereby promoting activation of innate immune cells. The accumulation of these components in various tissues and organs creates a pro-inflammatory microenvironment, characterized by a surge in pro-inflammatory cytokines, chemokines, reactive oxygen species, and type I interferons. Concurrently, single gene mutation-associated defects in the adaptive immune system give rise to the emergence of autoreactive T cells, hyperactivated B cells and plasma cells. The ensuing spectrum of cytokines and autoimmune antibodies drives systemic disease manifestations, primarily including kidney, skin and central nervous system-related phenotypes. This review provides a thorough overview of the single gene mutations and potential consequent immune dysregulations in monogenic lupus, elucidating the pathogenic mechanisms of monogenic lupus. Furthermore, it discusses the recent advances made in the therapeutic interventions for monogenic lupus.
摘要：
单基因狼疮,系统性红斑狼疮（SLE）的独特变体，以早期发作为特征，以家庭为中心的聚类，和提高疾病的严重程度。到目前为止,超过30种遗传变异已被鉴定为SLE和狼疮样表型的单基因病因。这些基因突变在破坏各种免疫途径中的关键作用越来越被认识到。特别是,先天免疫内单基因突变驱动的功能障碍，特别是补充系统的缺陷，阻碍游离核酸和免疫复合物的降解，从而促进先天免疫细胞的激活。这些成分在各种组织和器官中的积累产生了促炎的微环境，以促炎细胞因子激增为特征，趋化因子,活性氧，和I型干扰素。同时,适应性免疫系统中与单基因突变相关的缺陷导致自身反应性T细胞的出现，过度活化的B细胞和浆细胞。随后的细胞因子和自身免疫抗体谱驱动全身性疾病表现，主要包括肾脏，皮肤和中枢神经系统相关表型。本文综述了单基因狼疮的单基因突变和潜在的免疫失调。阐明单基因狼疮的致病机制。此外，它讨论了单基因性狼疮治疗干预措施的最新进展。
