Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels
Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels
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DOI：
10.1038/sj.ki.5002185
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发表时间：
2007-06-01
影响因子：
19.6
通讯作者：
Novak, J.
中科院分区：
文献类型：
--
作者：
Moldoveanu, Z.;Wyatt, R. J.;Novak, J.
免疫球蛋白A(IgA)肾病是世界上最常见的肾小球肾炎。准确的诊断需要肾活检，因为目前还没有方便的生物标志物可用。我们开发了一种血清学试验，基于观察到这种肾病的特征是循环中和系膜免疫沉积中的低半乳糖化IgA1。在没有半乳糖的情况下，IgA1铰链区O-连接链的末端糖是末端或唾液酸化的N-乙酰半乳糖胺。利用螺旋藻中识别N-乙酰半乳糖胺的凝集素，建立了检测血清中缺乏半乳糖的IgA1的酶联免疫吸附分析方法。153例未进展为终末期肾病的高加索成人患者的血清凝集素结合IgA1水平显著高于150名健康的高加索成人对照组。由于对照组的凝集素结合IgA1水平不是正态分布，因此使用第90个百分位数来确定显著升高。以1076U/ml为正常上限，153例IgA肾病患者中117例血清凝集素结合IgA1水平升高。其诊断敏感性为76.5%，特异性为94%，阳性预测值为88.6%，阴性预测值为78.9%。我们认为，这种凝集素结合试验有可能成为一种无创诊断IgA肾病的方法。
Immunoglobulin A (IgA) nephropathy is the most prevalent form of glomerulonephritis worldwide. A renal biopsy is required for an accurate diagnosis, as no convenient biomarker is currently available. We developed a serological test based upon the observation that this nephropathy is characterized by undergalactosylated IgA1 in the circulation and in mesangial immune deposits. In the absence of galactose, the terminal saccharide of O-linked chains in the hinge region of IgA1 is terminal or sialylated N-acetylgalactosamine. A lectin from Helix aspersa, recognizing N-acetylgalactosamine, was used to develop an enzyme-linked immunosorbent assay that measures galactose-deficient IgA1 in serum. The median serum lectin-binding IgA1 level was significantly higher for 153 Caucasian adult patients with IgA nephropathy without progression to end-stage renal disease as compared with that for 150 healthy Caucasian adult controls. As the lectin-binding IgA1 levels for the controls were not normally distributed, the 90th percentile was used for determination of significant elevation. Using a value of 1076 U/ml as the upper limit of normal, 117 of the 153 patients with IgA nephropathy had an elevated serum lectin-binding IgA1 level. The sensitivity as a diagnostic test was 76.5%, with specificity 94%; the positive predictive value was 88.6% and the negative predictive value was 78.9%. We conclude that this lectin-binding assay may have potential as a noninvasive diagnostic test for IgA nephropathy.