Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA deposition based upon heterogeneity in the composition of immune complexes in IgA nephropathy.

Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA deposition based upon heterogeneity in the composition of immune complexes in IgA nephropathy.
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DOI:
10.1186/1471-2369-15-89
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发表时间:
2014-06-13
期刊:
影响因子:
2.3
通讯作者:
Tomino Y
Tomino Y
中科院分区:
医学4区
文献类型:
--
作者:
Satake K;Shimizu Y;Sasaki Y;Yanagawa H;Suzuki H;Suzuki Y;Horikoshi S;Honda S;Shibuya K;Shibuya A;Tomino Y

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尽管伊加肾病(IgAN)患者血清低O-糖基化IgA 1可能比高O-糖基化IgA 1更优先存款于肾小球,但肾小球伊加沉积水平与血清IgA 1 O-聚糖谱之间的关系尚不清楚。采用酶联免疫吸附试验(ELISA)检测32例IgAN患者血清中总的O-糖基化IgA 1水平。采用小鼠Fcα/μ受体(mFcα/μR)转染子和流式细胞术(pIgA 1 trap),通过原始方法选择性测定血清低O-糖基化多聚IgA 1(pIgA 1)。通过对活检标本的免疫荧光进行图像分析,定量整个肾小球中伊加沉积的面积百分比(面积-IgA)。评估了面积-IgA与HAA-ELISA或pIgA 1陷阱数据之间的相关性。应用数据挖掘方法分析HAA-ELISA和pIgA 1 trap检测结果与临床指标的关系。当测量时,IgAN患者中O-糖基化不足的IgA 1水平显著高于健康对照(p < 0.05),而O-糖基化不足的pIgA 1没有显著差异。在IgAN患者(r2 = 0.005)中,HAA-ELISA和pIgA 1 trap的数据(r2 = 0.09)之间既没有观察到相关性,也没有观察到面积-IgA与HAA-ELISA或pIgA 1 trap的数据之间的线性相关性(分别为r2 = 0.005,0.03)。临床参数与HAA-ELISA和pIgA 1陷阱数据的等值线图显示,每个临床参数得分高的患者集中在特定区域,表明具有特异性IgA 1 O-聚糖谱的患者具有相似的临床参数。决策树分析表明,肾小球免疫复合物主要由IgA 1-IgG和补体、pIgA 1和补体、单体IgA 1-伊加或聚集的单体IgA 1组成。基于IgAN患者肾小球免疫复合物组成的异质性,血清低-O-糖基化IgA 1水平与肾小球伊加沉积无关。
Although serum under-O-glycosylated IgA1 in IgA nephropathy (IgAN) patients may deposit more preferentially in glomeruli than heavily-O-glycosylated IgA1, the relationship between the glomerular IgA deposition level and the O-glycan profiles of serum IgA1 remains obscure. Serum total under-O-glycosylated IgA1 levels were quantified in 32 IgAN patients by an enzyme-linked immunosorbent assay (ELISA) with Helix aspersa (HAA) lectin. Serum under-O-glycosylated polymeric IgA1 (pIgA1) was selectively measured by an original method using mouse Fcα/μ receptor (mFcα/μR) transfectant and flow cytometry (pIgA1 trap). The percentage area of IgA deposition in the whole glomeruli (Area-IgA) was quantified by image analysis on the immunofluorescence of biopsy specimens. Correlations were assessed between the Area-IgA and data from HAA-ELISA or pIgA1 trap. The relationships between clinical parameters and data from HAA-ELISA or pIgA1 trap were analyzed by data mining approach. While the under-O-glycosylated IgA1 levels in IgAN patients were significantly higher than those in healthy controls when measured (p < 0.05), there was no significant difference in under-O-glycosylated pIgA1. There was neither a correlation observed between the data from HAA-ELISA and pIgA1 trap (r2 = 0.09) in the IgAN patients (r2 = 0.005) nor was there a linear correlation between Area-IgA and data from HAA-ELISA or the pIgA1 trap (r2 = 0.005, 0.03, respectively). Contour plots of clinical parameters versus data from HAA-ELISA and the pIgA1 trap revealed that patients with a high score in each clinical parameter concentrated in specific areas, showing that patients with specific O-glycan profiles of IgA1 have similar clinical parameters. A decision tree analysis suggested that dominant immune complexes in glomeruli were consisted of: 1) IgA1-IgG and complements, 2) pIgA1 and complements, and 3) monomeric IgA1-IgA or aggregated monomeric IgA1. Serum under-O-glycosylated IgA1 levels are not correlated with glomerular IgA deposition based upon heterogeneity in the composition of glomerular immune complexes in IgAN patients.
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