Renal AH Amyloidosis Associated With a Truncated Immunoglobulin Heavy Chain Undetectable by Immunostaining
Renal AH Amyloidosis Associated With a Truncated Immunoglobulin Heavy Chain Undetectable by Immunostaining
复制标题
DOI：
10.1053/j.ajkd.2015.08.016
复制
发表时间：
2015-12-01
影响因子：
13.2
通讯作者：
Nagata, Michio
中科院分区：
文献类型：
--
作者：
Manabe, Shun;Hatano, Michiyasu;Nagata, Michio
AH淀粉样变性是一种罕见的由单克隆免疫球蛋白重链沉积引起的淀粉样变性。关键的诊断特征是单一类别免疫球蛋白重链的阳性免疫染色。我们报告一例AH淀粉样变性伴免疫球蛋白G（IgG）λ单克隆丙种球蛋白病，经肾组织免疫染色免疫球蛋白重链阴性后，经液相色谱-串联质谱（LC-MS/MS）诊断。纯化的肾淀粉样蛋白的分子量类似于11 kDa，其通过LC-MS/MS分析确定为对应于包含IgG重链的可变区和恒定区的截短部分的氨基酸序列。通过LC-MS/MS从患者血清中分离的蛋白质检测到完全相同的截短重链，表明截短的血清蛋白质是淀粉样蛋白的前体。由于免疫球蛋白重链的抗体识别Fc部分，因此恒定区中的大缺失可以解释免疫染色时的阴性结果。通过LC-MS/MS直接检测蛋白质是诊断肾AH淀粉样变性的有力辅助手段，特别是当免疫球蛋白染色结果与背景单克隆丙种球蛋白病不一致时。(C)2015年，美国国家肾脏基金会（National Kidney Foundation，Inc.）
AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) lambda monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was similar to 11 kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy. (C) 2015 by the National Kidney Foundation, Inc.