Novak Jan, Rizk Dana, Takahashi Kazuo, Zhang XianWen, Bian Qi, Ueda Hirouki, Ueda Yoshimi, Reily Colin, Lai Ling-Yun, Hao Chuanming, Novak Lea, Huang Zhi-Qiang, Renfrow Matthew B, Suzuki Hitoshi, Julian Bruce A
University of Alabama at Birmingham, Birmingham, AL, USA.
University of Alabama at Birmingham, Birmingham, AL, USA ; School of Medicine, Fujita Health University, Toyoake, Japan.
Kidney Dis (Basel). 2015 May;1(1):8-18. doi: 10.1159/000382134. Epub 2015 May 1.
IgA nephropathy, a frequent cause of end-stage renal disease, is an autoimmune disease wherein immune complexes consisting of IgA1 with galactose-deficient -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 -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.
IgA肾病是终末期肾病的常见病因，是一种自身免疫性疾病，其中由带有缺乏半乳糖聚糖的IgA1（自身抗原）和抗聚糖自身抗体组成的免疫复合物沉积于肾小球并导致肾损伤。已鉴定出多个与疾病风险相关的基因位点。风险等位基因的患病率在地理上存在差异，在东亚和北欧最高，在欧洲其他地区和北美较少，在非洲最少。IgA肾病通过肾活检标本的病理评估来诊断。目前，治疗并非针对疾病本身，而是侧重于控制血压和蛋白尿，理想情况下是抑制血管紧张素II。不同国家可能有其他不同的治疗方法。需要针对疾病的治疗方法以及用于诊断、预后和评估治疗反应的新工具。
已确定与IgA1异常糖基化相关的糖基化途径，从而导致自身抗原的产生。此外，还发现了IgA肾病中自身抗体的独特特征。IgA肾病患者和过敏性紫癜肾炎患者有许多这些生化特征相同，这表明这两种疾病可能代表疾病过程谱的两端。了解致病性含IgA1免疫复合物形成所涉及的分子机制将有助于开发针对疾病的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，由致肾炎循环免疫复合物在肾小球沉积引起，该复合物由抗聚糖自身抗体结合的缺乏半乳糖的IgA1（自身抗原）组成。更好地理解IgA肾病发病机制的多步骤过程以及遗传和环境促成因素将有助于开发生物标志物，以识别可能从未来针对疾病的治疗中获益的进行性疾病患者。
