Aberrantly Glycosylated IgA1 in IgA Nephropathy: What We Know and What We Don't Know.
Aberrantly Glycosylated IgA1 in IgA Nephropathy: What We Know and What We Don't Know.
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DOI：
10.3390/jcm10163467
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发表时间：
2021-08-05
影响因子：
3.9
通讯作者：
Takahashi K
中科院分区：
文献类型：
--
作者：
Ohyama Y;Renfrow MB;Novak J;Takahashi K
伊加肾病（IgAN）是世界范围内最常见的原发性肾小球疾病，其特征在于含有IgA 1的免疫复合物在肾小球沉积。IgA 1铰链区（HR）有多达6个成簇的O-聚糖，由Ser/Thr连接的N-乙酰半乳糖胺组成，通常含有β 1，3-连接的半乳糖和可变的唾液酸化。在IgAN患者中，具有异常O-糖基化HR的IgA 1（称为半乳糖缺陷型IgA 1（Gd-IgA 1））的循环水平升高。目前的证据表明，IgAN是由多个连续的致病步骤诱导的，并且异常糖基化的IgA 1的产生被认为是初始步骤。因此，异常糖基化的IgA 1的生物合成的机制和异常糖型的IgA 1在疾病发展中的参与已经被研究。此外，Gd-IgA 1代表IgAN的有吸引力的生物标志物，其临床意义仍在评估中。为了阐明IgAN的发病机制，重要的是去卷积Gd-IgA 1的生物合成来源，并表征致病性IgA 1 HR O-糖型，包括聚糖结构及其附着位点。这些努力可能会导致新的生物标志物的开发。在这里，我们回顾了IgA 1 HR O-糖基化的一般和异常糖基化的IgA 1在IgA肾病的发病机制中的作用，特别是。
IgA nephropathy (IgAN), the most common primary glomerular disease worldwide, is characterized by glomerular deposition of IgA1-containing immune complexes. The IgA1 hinge region (HR) has up to six clustered O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine usually with β1,3-linked galactose and variable sialylation. Circulating levels of IgA1 with abnormally O-glycosylated HR, termed galactose-deficient IgA1 (Gd-IgA1), are increased in patients with IgAN. Current evidence suggests that IgAN is induced by multiple sequential pathogenic steps, and production of aberrantly glycosylated IgA1 is considered the initial step. Thus, the mechanisms of biosynthesis of aberrantly glycosylated IgA1 and the involvement of aberrant glycoforms of IgA1 in disease development have been studied. Furthermore, Gd-IgA1 represents an attractive biomarker for IgAN, and its clinical significance is still being evaluated. To elucidate the pathogenesis of IgAN, it is important to deconvolute the biosynthetic origins of Gd-IgA1 and characterize the pathogenic IgA1 HR O-glycoform(s), including the glycan structures and their sites of attachment. These efforts will likely lead to development of new biomarkers. Here, we review the IgA1 HR O-glycosylation in general and the role of aberrantly glycosylated IgA1 in the pathogenesis of IgAN in particular.
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