Mass Spectrometry-Based Proteomic Diagnosis of Renal Immunoglobulin Heavy Chain Amyloidosis
Mass Spectrometry-Based Proteomic Diagnosis of Renal Immunoglobulin Heavy Chain Amyloidosis
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DOI：
10.2215/cjn.02890310
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发表时间：
2010-12-01
影响因子：
9.8
通讯作者：
Dogan, Ahmet
中科院分区：
文献类型：
--
作者：
Sethi, Sanjeev;Theis, Jason D.;Dogan, Ahmet
背景和目的：淀粉样变性是一组以细胞外蛋白质沉积为不溶性聚集体积累为特征的疾病。淀粉样变的临床管理是基于确定潜在的病因和淀粉样蛋白的准确分型。累及肾脏的重链淀粉样蛋白很难被识别，常常使诊断陷入困境。设计，设置，参与者和措施：在本研究中，我们描述了使用激光显微解剖（LMD）和质谱（MS）为基础的蛋白质组学分析，以准确分型14例淀粉样变性。我们还描述了4例肾脏Ig重链淀粉样变的临床病理结果，这些病例需要LMD/MS蛋白质组学分析来准确分型淀粉样蛋白。结果：4例Ig重链肾淀粉样变性患者的LMD/MS蛋白组学数据显示Ig重链伴或不伴轻链。Ig重链的断裂情况如下：1例为Ig γ 1链恒定区和λ轻链，1例为Ig α链恒定区和kappa轻链可变和恒定区，2例为Ig γ 3链恒定区和重链可变区I和/或III区，无轻链。我们比较了Ig重链肾淀粉样蛋白与其他类型淀粉样蛋白的LMD/MS蛋白质组学数据，包括Ig轻链、血清淀粉样蛋白A、纤维蛋白原A- α链肾淀粉样蛋白和转甲状腺素淀粉样蛋白。结论：LMD/MS是诊断肾淀粉样变性（包括Ig重链淀粉样蛋白）和准确分型的一种敏感、特异的工具。中华临床医学杂志，2010,29(5):518 - 518。doi: 10.2215 / CJN.02890310
Background and objectives: Amyloidosis is a group of disorders characterized by accumulation of extracellular deposition of proteins as insoluble aggregates. The clinical management of amyloidosis is based on identifying the underlying etiology and accurate typing of the amyloid. Ig heavy chain amyloid involving the kidney is poorly recognized and often poses a diagnostic dilemma.Design, setting, participants, & measures: In this study, we describe the use of laser microdissection (LMD) and mass spectrometry (MS)-based proteomic analysis for the accurate typing of 14 cases of amyloidosis. We also describe the clinicopathologic findings of four problematic cases of renal Ig heavy chain amyloidosis that required LMD/MS proteomic analysis for accurate typing of the amyloid.Results: LMD/MS proteomic data of four cases of Ig heavy chain renal amyloidosis showed Ig heavy chains with or without light chains. The break up of the Ig heavy chains was as follows: one case showed Ig gamma 1 chain constant region and lambda light chains, one case showed Ig alpha chain constant region and kappa light chains variable and constant regions, whereas two cases showed Ig gamma 3 chain constant region and heavy chains variable region I and/or III without light chains. We compare the LMD/MS proteomic data of Ig heavy chain renal amyloid with that of other types of amyloid, including Ig light chains, serum amyloid A, fibrinogen A-alpha chain renal amyloid, and transthyretin amyloid.Conclusions: We conclude that LMD/MS is a sensitive and specific tool for diagnosis and accurate typing of renal amyloidosis, including Ig heavy chain amyloid. Clin J Am Soc Nephrol 5: 2180-2187, 2010. doi: 10.2215/CJN.02890310