Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy
Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy
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DOI：
10.1046/j.1523-1755.2001.0590031077.x
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发表时间：
2001-03-01
影响因子：
19.6
通讯作者：
Maeda, K
中科院分区：
文献类型：
--
作者：
Hiki, Y;Odani, H;Maeda, K
背景。IgA1分子主要沉积在IgA肾病（IgAN）的肾小球中，是一种独特的血清糖蛋白，因为它在其铰链区具有o -聚糖侧链。本研究旨在探讨igan患者肾小球IgA1中o -聚糖的结构。从278例IgAN患者的290份肾活检标本和4份血清IgA1样本中分离出IgA1 （IgAN, 2；对照，2）。采用基质辅助激光解吸电离飞行时间质谱法测定IgA1铰链糖肽的精确分子量，确定了o -聚糖糖型的种类。与对照组相比，IgAN组肾小球和血清IgA1中IgA1铰链糖肽的峰值分布明显向较小的分子量转移。在各样品IgA1铰链糖肽的5个主要峰中，IgAN患者沉积和血清IgA1中构成o -聚糖（GalNAc、Gal和NANA）的碳水化合物数量明显少于对照组。在IgAN中，肾小球IgA1铰链处的o聚糖侧链高度低糖基化。这些结果表明IgA1铰链糖肽的唾液化和半乳糖化减少在IgAN的肾小球沉积中起着至关重要的作用。
Background. The IgA1 molecule, which is predominantly deposited in glomeruli in IgA nephropathy (IgAN), is a unique serum glycoprotein because it has O-glycan side chains in its hinge region. Our study was conducted to investigate the O-glycan structure in the glomerular IgA1 in IgAN.Methods. The IgA1 was separated from 290 renal biopsy specimens of 278 IgAN patients and from four serum IgA1 samples (IgAN, 2; control, 2). The variety of O-glycan glycoform was determined by estimating the precise molecular weights of the IgA1 hinge glycopeptides using matrix-assisted laser desorption ionization time of flight mass spectrometry.Results. The peak distribution of IgA1 hinge glycopeptides clearly shifted to lesser molecular weights in both glomerular and serum IgA1 in IgAN compared with the serum IgA1 of controls. In the five major peaks of IgA1 hinge glycopeptides in each sample, the numbers of carbohydrates composing O-glycans (GalNAc, Gal, and NANA) in the deposited and serum IgA1 in IgAN patients were significantly fewer than those in the serum IgA1 in the control groups.Conclusion. The O-glycan side chains in the hinge of the glomerular IgA1 were highly underglycosylated in IgAN. These results indicate that the decreased sialylation and galactosylation of the IgA1 hinge glycopeptides play a crucial role in its glomerular deposition in IgAN.