DnaJ Heat Shock Protein Family B Member 9 Is a Novel Biomarker for Fibrillary GN
DnaJ Heat Shock Protein Family B Member 9 Is a Novel Biomarker for Fibrillary GN
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DOI：
10.1681/asn.2017030306
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发表时间：
2018-01-01
影响因子：
13.6
通讯作者：
Kurtin, Paul J.
中科院分区：
文献类型：
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作者：
Dasari, Surendra;Alexander, Mariam P.;Kurtin, Paul J.
原纤维性肾小球坏死（FGN）是一种罕见的原发性肾小球疾病。FGN的组织学和组织化学特征与其他肾小球疾病的组织学和组织化学特征重叠，尚未确定诊断FGN的独特组织学生物标志物。我们分析了患者活检标本肾小球的蛋白质组学含量，发现ddnaj热休克蛋白家族（Hsp40）成员B9 （DNAJB9）是FGN肾小球中含量第4高的蛋白质。与淀粉样变性肾小球相比，FGN肾小球DNAJB9蛋白的过表达是淀粉样变性肾小球的6倍。Sanger测序和蛋白质序列覆盖图显示，沉积在FGN肾小球中的DNAJB9蛋白没有任何主要的序列或结构改变。值得注意的是，我们在所有FGN患者中检测到DNAJB9，但在健康肾小球或19种非FGN肾小球疾病中未检测到。我们还观察到DNAJB9和Ig-g的共沉积。总的来说，这些发现表明DNAJB9是一个具有100%敏感性和100%特异性的FGN标记物。DNAJB9在FGN中过量的程度和特异性也表明该蛋白在FGN发病机制中起作用。有了这些证据，我们提出DNAJB9是肾活检标本中快速诊断FGN的强有力的生物标志物。
Fibrillary GN (FGN) is a rare primary glomerular disease. Histologic and histochemical features of FGN overlap with those of other glomerular diseases, and no unique histologic biomarkers for diagnosing FGN have been identified. We analyzed the proteomic content of glomeruli in patient biopsy specimens and detectedDnaJ heat shock protein family (Hsp40) member B9 (DNAJB9) as the fourth most abundant protein in FGN glomeruli. Compared with amyloidosis glomeruli, FGN glomeruli exhibited a.6-fold overexpression of DNAJB9 protein. Sanger sequencing and protein sequence coverage maps showed that the DNAJB9 protein deposited in FGN glomeruli did not have any major sequence or structural alterations. Notably, we detected DNAJB9 in all patients with FGN but not in healthy glomeruli or in 19 types of non-FGN glomerular diseases. We also observed the codeposition of DNAJB9 and Ig-g. Overall, these findings indicate that DNAJB9 is an FGN marker with 100% sensitivity and 100% specificity. The magnitude and specificity of DNAJB9 overabundance in FGN also suggests that this protein has a role in FGN pathogenesis. With this evidence, we propose that DNAJB9 is a strong biomarker for rapid diagnosis of FGN in renal biopsy specimens.