Nephrology, Dialysis, and Renal Transplantation Department, University North Hospital, 42055 Saint-Etienne Cedex 2, France.
J Am Soc Nephrol. 2012 Sep;23(9):1579-87. doi: 10.1681/ASN.2012010053. Epub 2012 Aug 16.
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≤0.01). Furthermore, increasing levels correlated with worse clinical outcomes. In Cox regression and Kaplan-Meier analyses, IgG autoantibody levels ≥1.33 predicted dialysis or death (both P≤0.01). In conclusion, these data suggest that serum levels of IgG and IgA autoantibodies strongly associate with the progression of IgAN nephropathy.
系膜和循环 IgA1 具有异常糖基化铰链区 O-聚糖，是 IgA 肾病（IgAN）的特征。与健康个体不同，一些 IgA1 在 IgAN 患者中缺乏半乳糖，使铰链区暴露末端 N-乙酰半乳糖胺残基。识别这种缺乏半乳糖的 IgA1 作为自身抗原的循环自身抗体，或自身抗原本身的水平，可能允许预测疾病进展。在这里，我们根据绝对肾脏进展为透析或死亡的风险（0，极低；1，低；2，高；3，极高），从我们的前瞻性队列中选择了 97 例 IgAN 患者的诊断时血清样本，分析了来自自身抗原和自身抗体的分析物。我们还分析了来自包括 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，与合并对照组相比，患者的总自身抗原、归一化 IgG 自身抗体和总 IgA 自身抗体的血清水平明显更高（均 P≤0.01）。此外，水平升高与更差的临床结局相关。在 Cox 回归和 Kaplan-Meier 分析中，IgG 自身抗体水平≥1.33 预测透析或死亡（均 P≤0.01）。总之，这些数据表明，IgG 和 IgA 自身抗体的血清水平与 IgAN 肾病的进展密切相关。
