New Insights into the Pathogenesis of IgA Nephropathy.
New Insights into the Pathogenesis of IgA Nephropathy.
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DOI：
10.1159/000382134
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
Julian BA
中科院分区：
文献类型：
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作者：
Novak J;Rizk D;Takahashi K;Zhang X;Bian Q;Ueda H;Ueda Y;Reily C;Lai LY;Hao C;Novak L;Huang ZQ;Renfrow MB;Suzuki H;Julian BA
IgA肾病是终末期肾脏疾病的常见病因，是一种自身免疫性疾病，其中IgA1与半乳糖缺乏的o -聚糖（自身抗原）和抗聚糖自身抗体组成的免疫复合物沉积在肾小球并诱导肾损伤。已经确定了与疾病风险相关的多个遗传位点。风险等位基因的流行率因地而异，在东亚和北欧最高，在欧洲和北美其他地区较少，在非洲最低。IgA肾病是通过肾活检标本的病理评估来诊断的。目前，治疗不是针对疾病，而是侧重于维持血压和蛋白尿的控制，理想情况下是抑制血管紧张素II。各国之间可能采取的其他措施有所不同。需要疾病特异性治疗以及诊断、预后和治疗反应评估的新工具。与IgA1异常o -糖基化相关的糖基化途径以及自身抗原的产生已被确定。此外，还发现了IgA肾病自身抗体的独特特征。许多这些生化特征是IgA肾病和Henoch-Schönlein紫癜性肾炎患者共有的，这表明这两种疾病可能代表了疾病过程谱系的相反两端。了解致病性含iga1免疫复合物形成的分子机制将有助于开发疾病特异性治疗方法以及诊断和预后生物标志物。IgA肾病是一种自身免疫性疾病，由肾小球沉积引起的肾源性循环免疫复合物由半乳糖缺乏的IgA1（自身抗原）与抗多糖自身抗体结合而成。更好地了解IgA肾病发病的多步骤过程以及遗传和环境因素将导致开发生物标志物来识别进行性疾病患者，这些患者将从未来的疾病特异性治疗中受益。
IgA nephropathy, a frequent cause of end-stage renal disease, is an autoimmune disease wherein immune complexes consisting of IgA1 with galactose-deficient O-glycans (autoantigen) and anti-glycan autoantibodies deposit in glomeruli and induce renal injury. Multiple genetic loci associated with disease risk have been identified. The prevalence of risk alleles varies geographically, highest in eastern Asia and northern Europe, fewer in other parts of Europe and North America, and the least in Africa. IgA nephropathy is diagnosed from pathological assessment of a renal biopsy specimen. Currently, therapy is not disease-targeted but rather is focused on maintaining control of blood pressure and proteinuria, ideally with suppression of angiotensin II. Possible additional approaches differ between countries. Disease-specific therapy as well as new tools for diagnosis, prognosis, and assessment of responses to therapy are needed. Glycosylation pathways associated with aberrant O-glycosylation of IgA1 and, thus, production of autoantigen, have been identified. Furthermore, unique characteristics of the autoantibodies in IgA nephropathy have been uncovered. Many of these biochemical features are shared by patients with IgA nephropathy and Henoch-Schönlein purpura nephritis, suggesting that the two diseases may represent opposite ends of a spectrum of a disease process. Understanding the molecular mechanisms involved in formation of pathogenic IgA1-containing immune complexes will enable development of disease-specific therapies as well as diagnostic and prognostic biomarkers. IgA nephropathy is an autoimmune disease caused by glomerular deposition of nephritogenic circulating immune complexes consisting of galactose-deficient IgA1 (autoantigen) bound by anti-glycan autoantibodies. A better understanding of the multi-step process of pathogenesis of IgA nephropathy and the genetic and environmental contributing factors will lead to development of biomarkers to identify patients with progressive disease who would benefit from a future disease-specific therapy.