Genetic regulation of serum cytokines in systemic lupus erythematosus
Genetic regulation of serum cytokines in systemic lupus erythematosus
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DOI：
10.1016/j.trsl.2009.08.012
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发表时间：
2010-03-01
影响因子：
7.8
通讯作者：
Niewold, Timothy B.
中科院分区：
文献类型：
--
作者：
Kariuki, Silvia N.;Niewold, Timothy B.
近年来，系统性红斑狼疮（SLE）的遗传关联研究非常成功，确定了几个与疾病易感性相关的基因座。还有很多工作要做，以整合这些基因位点的功能性致病途径的特点，疾病。我们的工作假设是，与SLE和自身免疫相关的许多遗传变异通过改变细胞因子谱或对细胞因子信号的反应来介导疾病的风险。影响细胞因子信号传导的遗传多态性可以改变免疫应答的阈值，导致自身抗原的促炎呈递和随后的针对自身的适应性免疫的误导，这在自身免疫性疾病中观察到。SLE在临床上是异质性的，遗传学上是复杂的，我们预计个体基因和细胞因子模式对不同的疾病表现和患者亚群或多或少是重要的。定义这些基因型-细胞因子-表型关系将增加我们对初始疾病发病机制以及随后对各种治疗的反应/无反应的理解。在这篇综述中，我们总结了一些最新的工作在该地区的SLE细胞因子遗传学和描述的影响，SLE，自身免疫和免疫系统的稳态，这是揭示了这些调查。（翻译研究2010;155：109-117）
Genetic association studies in systemic lupus erythematosus (SLE) have been extremely successful in recent years, identifying several loci associated with disease susceptibility. Much work remains to integrate these loci into the functional pathogenic pathways that characterize the disease. Our working hypothesis is that many genetic variations linked to SLE and autoimmunity mediate the risk of disease by altering cytokine profiles or responses to cytokine signaling. Genetic polymorphisms that affect cytokine signaling could alter thresholds for immune responses, resulting in proinflammatory presentation of self-antigens and the subsequent misdirection of adaptive immunity against self, which is observed in autoimmune disease. SLE is clinically heterogeneous and genetically complex, and we expect that individual genes and cytokine patterns will be more or less important to different disease manifestations and subgroups of patients. Defining these genotype-cytokine-phenotype relationships will increase our understanding of both initial disease pathogenesis as well as subsequent response/nonresponse to various therapies. In this review, we summarize some recent work in the area of SLE cytokine genetics and describe the implications for SLE, autoimmunity, and immune system homeostasis, which are revealed by these investigations. (Translational Research 2010;155:109-117)