ApoL1 and the Immune Response of Patients with Systemic Lupus Erythematosus
ApoL1 and the Immune Response of Patients with Systemic Lupus Erythematosus
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DOI：
10.1007/s11926-017-0637-9
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发表时间：
2017-03-01
影响因子：
5
通讯作者：
Clancy, Robert M.
中科院分区：
文献类型：
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作者：
Blazer, Ashira D.;Clancy, Robert M.
综述目的系统性红斑狼疮（SLE）可使心血管疾病（CVD）的风险增加50倍，与欧洲裔美国人相比，患有SLE的非洲裔美国人的损伤加速，心血管风险增加一倍。最近的发现全基因组关联研究已经确定了22q13的实质性信号，现在被分配给载脂蛋白L1（APOL 1）的变异，这与进行性非糖尿病肾病，心血管疾病和许多免疫相关性肾脏疾病有关，包括狼疮性肾炎。我们认为，关键的APOL 1细胞内通路的改变可能是基于结构的相关疾病状态的基础，变异型和祖先型之间的功能差异。虽然祖先APOL1可能是自噬的关键驱动因素，但非保守的一级结构变化导致毒性功能增加，自噬减弱和无监督的孔形成特征。因此，不同的细胞内生物学途径的祖先和变体APOL1可能解释恶化的预后，如在SLE中所示。
Purpose of Review Systemic lupus erythematosus (SLE) confers up to a 50-fold increased risk of cardiovascular disease (CVD), and African Americans with SLE experience accelerated damage accrual and doubled cardiovascular risk when compared to their European American counterparts. Recent Findings Genome-wide association studies have identified a substantial signal at 22q13, now assigned to variation at apolipoprotein L1 (APOL1), which has associated with progressive nondiabetic nephropathy, cardiovascular disease, and many immune-associated renal diseases, including lupus nephritis.Summary We contend that alterations in crucial APOL1 intracellular pathways may underpin associated disease states based on structure-functional differences between variant and ancestral forms. While ancestral APOL1 may be a key driver of autophagy, nonconserved primary structure changes result in a toxic gain of function with attenuation of autophagy and an unsupervised pore-forming feature. Thus, the divergent intracellular biological pathways of ancestral and variant APOL1 may explain a worsened prognosis as demonstrated in SLE.