Laser Microdissection and Proteomic Analysis of Amyloidosis, Cryoglobulinemic GN, Fibrillary GN, and Immunotactoid Glomerulopathy
Laser Microdissection and Proteomic Analysis of Amyloidosis, Cryoglobulinemic GN, Fibrillary GN, and Immunotactoid Glomerulopathy
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DOI：
10.2215/cjn.07030712
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发表时间：
2013-06-01
影响因子：
9.8
通讯作者：
Nasr, Samih H.
中科院分区：
文献类型：
--
作者：
Sethi, Sanjeev;Theis, Jason D.;Nasr, Samih H.
背景和目的：淀粉样变性、肾小球肾炎和免疫类纤维化肾小球病中存在机化沉积物。然而，沉积物的成分尚不清楚。设计、设置、参与者和测量肾小球的激光显微切割，然后进行质谱分析，以确定沉积物的成分。结果将结果分为四大类：淀粉样蛋白，结构/其他蛋白，补体蛋白和免疫球蛋白。关于淀粉样蛋白，淀粉样变性（41.8 +/- 20.9）中载脂蛋白E的谱数较大，而肾小球病（15.6 +/- 12.5）和免疫类（12.3 +/- 12）中载脂蛋白E的谱数较大。载脂蛋白E在冷球蛋白血症性肾小球肾炎中缺失。血清淀粉样蛋白P组分在淀粉样变性中以大的谱数（14.1 +/- 6.7）存在，在免疫类淀粉样肾小球病中以小的谱数存在，但在肾小球肾炎和冷球蛋白血症性GN中不存在。然而，与肾小球肾炎（16.25 +/- 19.7）和冷球蛋白血症（13.3 +/- 4.9）相比，免疫类肾小球病（47.3 +/- 34.6）中存在大量的IG γ-1链C区。所有IG轻链相关性淀粉样变性病例均显示各自的IG轻链C区的光谱（平均值=10 +/- 1.7）。结论基于光谱数，研究表明载脂蛋白E与IG轻链C区/淀粉样蛋白或IG γ 1链C区的相对量与淀粉样变性、肾小球肾炎和免疫类肾小球病中沉积物的组织化有关。然而，载脂蛋白E的缺乏与缺乏纤维性存款在cryopulinemic GN。
Background and objectives Organized deposits are present in amyloidosis, fibrillary GN, and immunotactoid glomerulopathy. However, the constituents of the deposits are not known.Design, setting, participants, & measurements Laser microdissection of glomeruli followed by mass spectrometry was performed to determine the composition of the deposits. The results were compared with cryoglobulinemic GN.Results The results are divided into four major groups: amyloidogenic proteins, structural/other proteins, complement proteins, and Igs. With regards to amyloidogenic proteins, large spectra numbers of apolipoprotein E are noted in amyloidosis (41.8 +/- 20.9) compared with fibrillary (15.6 +/- 12.5) and immunotactoid (12.3 +/- 12) glomerulopathy. Apolipoprotein E was absent in cryoglobulinemic GN. Serum amyloid P component is present in large spectra numbers in amyloidosis (14.1 +/- 6.7) and small spectra numbers in immunotactoid glomerulopathy, but it is absent in fibrillary and cryoglobulinemic GN. However, large spectra numbers of Ig gamma-1 chain C region are present in immunotactoid glomerulopathy (47.3 +/- 34.6) compared with fibrillary (16.25 +/- 19.7) and cryoglobulinemic (13.3 +/- 4.9) GN. All cases of Ig light chain-associated amyloidosis showed spectra for the respective Ig light-chain C region (mean=10 +/- 1.7).Conclusions Based on the spectra numbers, the study shows that the relative amount of apolipoprotein E to Ig light-chain C region/amyloidogenic proteins or Ig gamma-1 chain C region is associated with the organization of the deposits in amyloidosis, fibrillary GN, and immunotactoid glomerulopathy. However, the absence of apolipoprotein E correlates with the lack of fibrillar deposits in cryoglobulinemic GN.