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Laser Microdissection and Proteomic Analysis of Amyloidosis, Cryoglobulinemic GN, Fibrillary GN, and Immunotactoid Glomerulopathy #MMPMID23411427
Sethi S; Theis JD; Vrana JA; Fervenza FC; Sethi A; Qian Q; Quint P; Leung N; Dogan A; Nasr SH
Clin J Am Soc Nephrol 2013[Jun]; 8 (6): 915-21 PMID23411427show ga
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 ?-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 ?-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.