In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy
In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy
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DOI：
10.1038/ki.2015.333
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发表时间：
2016-03-01
影响因子：
19.6
通讯作者：
Schena, Francesco P.
中科院分区：
文献类型：
--
作者：
Serino, Grazia;Pesce, Francesco;Schena, Francesco P.
免疫球蛋白A肾病（IgAN）是一种世界性疾病，其特征是肾小球系膜中存在半乳糖缺陷型IgA 1沉积。需要进行肾活检以进行诊断。在这里，我们测量了两种miRNAs（let-7 b和miR-148 b），以前被确定为IgA 1的O-糖基化过程的调节剂，在国际多中心研究中招募的IgAN患者和健康献血者（对照）的血清样本中。基于这些miRNA开发了两种预测模型，并通过分三步进行的受试者工作特征（ROC）曲线下面积（AUC）评估了组合生物标志物的诊断准确性。在一项训练研究中，组合的miRNA能够区分100名IgAN患者和119名对照（AUC，0.82）。一项验证研究在145名IgAN患者和64名对照的独立队列中证实了该模型（AUC，0.78）。最后，在一项测试研究中，组合的生物标志物能够区分IgAN患者和105名受其他形式原发性肾小球肾炎影响的患者，支持特异性（AUC，0.76）。使用相同的研究设计，我们还进行了两个亚组分析（一个针对高加索人，一个针对东亚人），发现种族特异性模型最适合区分IgAN患者和对照组。因此，联合的miRNA生物标志物let-7 b和miR-148 b的血清水平似乎是一种新的，可靠的，非侵入性的测试，以预测患有IgAN的概率。
Immunoglobulin A nephropathy (IgAN) is a worldwide disease characterized by the presence of galactose-deficient IgA1 deposits in the glomerular mesangium. A kidney biopsy for diagnosis is required. Here, we measured two miRNAs (let-7b and miR-148b), previously identified as regulators of the O-glycosylation process of IgA1, in serum samples from patients with IgAN and healthy blood donors (controls) recruited in an international multicenter study. Two predictive models, based on these miRNAs, were developed and the diagnostic accuracy of the combined biomarkers was assessed by the area under the receiver operating characteristic (ROC) curve (AUC) carried out in three steps. In a training study, the combined miRNAs were able to discriminate between 100 patients with IgAN and 119 controls (AUC, 0.82). A validation study confirmed the model in an independent cohort of 145 patients with IgAN and 64 controls (AUC, 0.78). Finally, in a test study, the combined biomarkers were able to discriminate patients with IgAN from 105 patients affected by other forms of primary glomerulonephritis, supporting the specificity (AUC, 0.76). Using the same study design, we also performed two subgroup analyses (one for Caucasians and one for East Asians) and found that race-specific models were the best fit to distinguish IgAN patients from controls. Thus, serum levels of the combined miRNA biomarker, let-7b and miR-148b, appears to be a novel, reliable, and noninvasive test to predict the probability of having IgAN.