Laboratório de Imunogenética, Departamento of Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
Laboratório de Imunologia dos Tumores, Departamento of Imunologia, Instituto de Ciências Biomédicas, USP, São Paulo, SP, Brazil.
Clin Immunol. 2018 Feb;187:46-49. doi: 10.1016/j.clim.2017.10.003. Epub 2017 Oct 12.
Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (p<0.01), and rs11651270 also with a lower risk of new renal events during follow-up (p=0.01). Supporting these findings, diabetes metabolites (glycated albumin and high glucose) were able to modulate NLRP1 expression. This study is the first to suggest a protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a homeostatic factor against metabolic stress.
尽管炎症小体在肾损伤的动物模型中发挥了众所周知的作用，但人类的相关研究有限，其在糖尿病肾病（DKD）中的参与情况尚不清楚。本研究旨在阐明炎症小体遗传学在 1 型糖尿病（T1D）中 DKD 发展中的作用。通过回顾性和前瞻性队列的多变量分析，评估了炎症小体基因的功能变体与 DKD 的相关性。NLRP1 rs2670660 和 rs11651270 多态性与发生 DKD 的风险降低显著相关（p<0.01），rs11651270 还与随访期间新的肾脏事件风险降低相关（p=0.01）。这些发现得到了支持，糖尿病代谢物（糖化白蛋白和高血糖）能够调节 NLRP1 的表达。这项研究首次表明 NLRP1 在 DKD 中具有保护作用，突出了 NLRP1 作为代谢应激的一种稳态因子的新兴作用。
