Autoantibodies Targeting Galactose-Deficient IgA1 Associate with Progression of IgA Nephropathy
Autoantibodies Targeting Galactose-Deficient IgA1 Associate with Progression of IgA Nephropathy
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DOI：
10.1681/asn.2012010053
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发表时间：
2012-09-01
影响因子：
13.6
通讯作者：
Novak, Jan
中科院分区：
文献类型：
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作者：
Berthoux, Francois;Suzuki, Hitoshi;Novak, Jan
系膜和循环IgA1与异常糖基化铰链区o -聚糖表征IgA肾病（IgAN）。与健康个体不同的是，IgAN患者的一些IgA1缺乏半乳糖，从而暴露出铰链区域的末端n -乙酰半乳糖胺残基。循环中的自身抗体识别出这种半乳糖缺乏的IgA1是一种自身抗原，或者这种自身抗原本身的水平，可以预测疾病的进展。在这里，我们分析了97名IgAN患者在诊断时获得的自身抗原和自身抗体的血清样本，这些患者从我们的前瞻性队列中选择，根据他们进展到透析或死亡的绝对肾脏风险（0，非常低；1，低；2，高；3，非常高）。我们还分析了来自30名健康志愿者和30名非igan疾病患者的对照样本。平均随访时间为13.8年。我们发现，患者的平均血清总自身抗原、归一化IgG自身抗体和总IgA自身抗体水平显著高于联合对照组（均P = 1.33）
Mesangial and circulating IgA1 with aberrantly glycosylated hinge region O-glycans characterize IgA nephropathy (IgAN). Unlike healthy individuals, some IgA1 is galactose deficient in patients with IgAN, leaving terminal N-acetylgalactosamine residues in the hinge region exposed. Circulating autoantibodies that recognize such galactose-deficient IgA1 as an autoantigen, or the levels of the autoantigen itself, may allow prediction of disease progression. Here, we analyzed serum samples obtained at diagnosis for autoantigen and autoantibodies from 97 patients with IgAN selected from our prospective cohort according to their absolute renal risk for progression to dialysis or death (0, very low; 1, low; 2, high; 3, very high). We also analyzed samples from controls comprising 30 healthy volunteers and 30 patients with non-IgAN disease. The mean follow-up was 13.8 years. We found that mean serum levels of total autoantigen, normalized IgG autoantibody, and total IgA autoantibody were significantly higher in patients than in the combined controls (all P = 1.33 predicted dialysis or death (both P5