Medullary amyloidosis associated with apolipoprotein A-IV deposition
Medullary amyloidosis associated with apolipoprotein A-IV deposition
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DOI：
10.1038/ki.2011.316
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发表时间：
2012-01-01
影响因子：
19.6
通讯作者：
Dogan, Ahmet
中科院分区：
文献类型：
--
作者：
Sethi, Sanjeev;Theis, Jason D.;Dogan, Ahmet
淀粉样变性是由蛋白质以不溶性方式在组织内的细胞外沉积引起的。在淀粉样变性的遗传形式中，甲状腺素运载蛋白、纤维蛋白原A-α、溶菌酶、凝溶胶蛋白、载脂蛋白A-I和A-II在组织斑块中积聚。我们报告一位52岁男性，无肾脏疾病家族史，表现为尿频、肾功能逐渐丧失，但无明显蛋白尿。肾活检发现大量的淀粉样蛋白局限于髓质，没有涉及肾小球或血管。甲状腺素运载蛋白或血清淀粉样蛋白A的免疫组织化学分析和潜在的单克隆丙种球蛋白病的测试均为阴性。虽然最初怀疑是淀粉样轻链淀粉样变性，但激光显微切割和质谱分析显示淀粉样蛋白由大量载脂蛋白A-IV组成。这是基于质谱研究，在三个显微切割样本中显示100、96和73个光谱，与载脂蛋白A-IV匹配的概率为100%。DNA分析检测到三种序列变异，代表载脂蛋白A-IV基因的常见多态性。因此，在这种情况下，载脂蛋白A-IV沉积和肾脏受累似乎仅限于髓质。诊断载脂蛋白A-IV淀粉样变性需要高度怀疑，因为如果肾活检仅包括皮质，可能会漏诊。Kidney International（2012）81，201-206; doi：10.1038/ki.2011.316; 2011年9月7日在线发表
Amyloidosis is caused by extracellular deposition of proteins in an insoluble manner within tissues. In hereditary forms of amyloidosis, transthyretin, fibrinogen A-alpha, lysozyme, gelsolin, apolipoprotein A-I, and A-II accumulate in the tissue plaques. Here we describe a 52-year-old man with no family history of renal disease who presented with increased urinary frequency, gradual loss of renal function but no significant proteinuria. Renal biopsy found large amounts of amyloid restricted to the medulla with no involvement of glomeruli or vessels. Immunohistochemical analysis for transthyretin or serum amyloid A and tests for an underlying monoclonal gammopathy were negative. Although initially suspected to be amyloid light chain amyloidosis, laser microdissection and mass spectrometry showed that the amyloid was composed of large amounts of apolipoprotein A-IV. This was based on mass spectrometry studies that showed 100, 96, and 73 spectra in three microdissected samples that matched to apolipoprotein A-IV with 100% probability. DNA analyses detected three sequence variants representing common polymorphisms of the apolipoprotein A-IV gene. Thus, in this case, apolipoprotein A-IV deposition and renal involvement appear to be restricted to the medulla. A high degree of suspicion is required for the diagnosis of apolipoprotein A-IV amyloidosis as it may be missed if a renal biopsy consists only of cortex. Kidney International (2012) 81, 201-206; doi:10.1038/ki.2011.316; published online 7 September 2011