IgA nephropathy
IgA nephropathy
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DOI：
10.1038/nrdp.2016.1
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发表时间：
2016-02-11
影响因子：
81.5
通讯作者：
Glassock, Richard J.
中科院分区：
文献类型：
--
作者：
Lai, Kar Neng;Tang, Sydney C. W.;Glassock, Richard J.
在全球范围内，IgA肾病(IgAN)是最常见的可进展为肾功能衰竭的原发性肾小球肾炎。IgAN的确切发病机制尚不清楚，但目前的生化和遗传学数据表明，异常糖基化的IgA1产生过多。这些异常免疫球蛋白的特征是某些铰链区O-连接糖链的半乳糖缺乏。然而，仅有异常的糖基化不足以引起肾脏损伤：需要识别低半乳糖化的IgA1分子的糖特异性IgA和IgG自身抗体的参与。肾小球沉积的免疫复合物含有低半乳糖化的IgA1，激活系膜细胞，导致局部细胞因子、趋化因子和补体的过度产生。新出现的数据表明，系膜来源的介质在系膜沉积IgA1后释放，通过体液串扰导致足细胞和肾小管间质损伤。患者可能出现一系列的体征和症状，从无症状的肉眼血尿到肉眼血尿。临床进展各不相同，30%-40%的患者在首次临床表现后20-30年达到终末期肾脏疾病。目前，还没有针对IgAN的特异性治疗方法，对患者的治疗目的是控制血压和维持肾功能。然而，新的治疗方法正在被开发，建立在我们对疾病发病机制的不断提高的理解上。
Globally, IgA nephropathy (IgAN) is the most common primary glomerulonephritis that can progress to renal failure. The exact pathogenesis of IgAN is not well defined, but current biochemical and genetic data implicate overproduction of aberrantly glycosylated IgA1. These aberrant immunoglobulins are characterized by galactose deficiency of some hinge-region O-linked glycans. However, aberrant glycosylation alone is insufficient to induce renal injury: the participation of glycan-specific IgA and IgG autoantibodies that recognize the undergalactosylated IgA1 molecule is required. Glomerular deposits of immune complexes containing undergalactosylated IgA1 activate mesangial cells, leading to the local overproduction of cytokines, chemokines and complement. Emerging data indicate that mesangial-derived mediators that are released following mesangial deposition of IgA1 lead to podocyte and tubulointerstitial injury via humoral crosstalk. Patients can present with a range of signs and symptoms, from asymptomatic microscopic haematuria to macroscopic haematuria. The clinical progression varies, with 30-40% of patients reaching end-stage renal disease 20-30 years after the first clinical presentation. Currently, no IgAN-specific therapies are available and patients are managed with the aim of controlling blood pressure and maintaining renal function. However, new therapeutic approaches are being developed, building upon our ever-improving understanding of disease pathogenesis.