Chee Kay Cheung, Suceena Alexander, Heather N. Reich, Haresh Selvaskandan, Hong Zhang, Jonathan Barratt
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引用次数: 0
摘要
IgA 肾病(IgAN)是原发性肾小球肾炎的一种常见形式,是全球慢性肾病的一个重要病因,观察性研究表明,大多数患者在有生之年都有发生肾衰竭的风险。一些研究进展使人们对疾病的发病机理有了更深入的了解,这种发病机理以多重打击模型为框架,即可能来自粘膜免疫系统的缺乏半乳糖的循环 IgA1 增加后,与特异性 IgG 和 IgA 抗体结合,产生沉积在肾小球内的免疫复合物,从而引发炎症、补体活化和肾脏损伤。虽然目前的治疗方案有限,但针对疾病发病机制中不同途径、细胞和介质的新疗法正在迅速出现,这些途径、细胞和介质包括肠道粘膜中的 B 细胞引物、细胞因子 APRIL 和 BAFF、浆细胞、补体激活和内皮素途径激活。随着更多治疗方法的问世,有可能改变许多 IgAN 患者的长期前景。
The pathogenesis of IgA nephropathy and implications for treatment
IgA nephropathy (IgAN) is a common form of primary glomerulonephritis and represents an important cause of chronic kidney disease globally, with observational studies indicating that most patients are at risk of developing kidney failure within their lifetime. Several research advances have provided insights into the underlying disease pathogenesis, framed by a multi-hit model whereby an increase in circulating IgA1 that lacks galactose from its hinge region — probably derived from the mucosal immune system — is followed by binding of specific IgG and IgA antibodies, generating immune complexes that deposit within the glomeruli, which triggers inflammation, complement activation and kidney damage. Although treatment options are currently limited, new therapies are rapidly emerging that target different pathways, cells and mediators involved in the disease pathogenesis, including B cell priming in the gut mucosa, the cytokines APRIL and BAFF, plasma cells, complement activation and endothelin pathway activation. As more treatments become available, there is a realistic possibility of transforming the long-term outlook for many individuals with IgAN.
期刊介绍:
Nature Reviews Nephrology aims to be the premier source of reviews and commentaries for the scientific communities it serves.
It strives to publish authoritative, accessible articles.
Articles are enhanced with clearly understandable figures, tables, and other display items.
Nature Reviews Nephrology publishes Research Highlights, News & Views, Comments, Reviews, Perspectives, and Consensus Statements.
The content is relevant to nephrologists and basic science researchers.
The broad scope of the journal ensures that the work reaches the widest possible audience.