DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN
DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN
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DOI：
10.1681/asn.2017050566
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发表时间：
2018-01-01
影响因子：
13.6
通讯作者：
Smith, Kelly D.
中科院分区：
文献类型：
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作者：
Andeen, Nicole K.;Yang, Han-Yin;Smith, Kelly D.
纤维性肾小球肾炎是一种发病机制不明的罕见肾小球肾炎，其特征是由IG和补体蛋白组成的随机排列的无分支纤维（12-24 nm）聚集在肾小球内。在这项研究中，我们使用质谱技术来全面定义肾小球蛋白质组在肾小球肾炎与对照组和非肾小球肾炎肾脏疾病。我们使用激光捕获显微切割技术从福尔马林固定和石蜡包埋的活检标本中分离肾小球，并使用液相色谱和数据依赖串联质谱法对其进行分析。这些研究将DnaJ同源物亚家族B成员9（DNAJB 9）鉴定为仅在肾小球肾炎病例中检测到的高采样蛋白质。肾小球肾炎患者肾小球蛋白质组也含有IgG 1作为优势IG和经典补体途径蛋白。在肾小球肾炎标本，免疫荧光和免疫组化与抗DNAJB 9抗体显示强大的和特定的染色的肾小球簇的分布，模仿的免疫沉积物。我们的研究结果确定DNAJB 9作为一个假定的自身抗原在肾小球肾炎，并建议IgG 1和经典的补体效应途径可能介质的破坏性肾小球损伤，在这种疾病。
Fibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12-24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry. These studies identified DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sampled protein detected only in fibrillary GN cases. The glomerular proteome of fibrillary GN cases also contained IgG1 as the dominant Ig and proteins of the classic complement pathway. In fibrillary GN specimens only, immunofluorescence and immunohistochemistry with an anti-DNAJB9 antibody showed strong and specific staining of the glomerular tufts in a distribution that mimicked that of the immune deposits. Our results identify DNAJB9 as a putative autoantigen in fibrillary GN and suggest IgG1 and classic complement effector pathways as likely mediators of the destructive glomerular injury in this disease.