Laser microdissection and proteomic analysis of amyloidosis, cryoglobulinemic GN, fibrillary GN, and immunotactoid glomerulopathy

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 resultswere comparedwith cryoglobulinemicGN. 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 γ-1 chain C region are present in immunotactoid glomerulopathy (47.3±34.6) comparedwith 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 γ-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.