title: Proteomics and mass spectrometry in the diagnosis of renal amyloidosis.
abstract: The amyloidoses are a 'group' of disorders, all of which are associated with deposits that display similar staining and ultrastructural features and are toxic to tissues. Many proteins-currently 31 protein types and many more variants-have been shown to undergo such transformations. Among the various currently known amyloidoses, there are marked differences with regard to their pathogenesis and incidence, while the associated clinical picture is frequently overlapping. However, the therapies that are currently available are amyloid-type specific. The diagnosis of amyloidosis thus involves two steps: (i) a generic diagnosis, followed by (ii) an amyloid type-specific diagnosis or 'amyloid typing'. Immunofluorescence in frozen sections or immunohistochemistry (IHC) in paraffin sections has traditionally been used in the typing of amyloid. However, IHC of amyloid differs significantly from IHC in other areas of surgical pathology; both caution and experience are necessary for its interpretation. The rationale for the application of proteomic methods to amyloid typing lies in the relative abundance of amyloid proteins in tissue where, frequently, it is the 'dominant' protein. Proteomic techniques include the following steps: sample preparation, protein extraction and digestion into peptide fragments, followed by their subsequent separation and measurement by mass spectrometry (MS) and protein identification by informatics. The advantages as well as the limitations of both methods-immunohistochemistry and MS-based proteomics-are discussed. The current recommendations for the application of proteomics in renal amyloidosis are summarized.
authors.affiliation: Department of Pathology , Loyola University Medical Center , Chicago, IL , USA.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Picken
keywords: amyloid typing; amyloidosis; immunohistochemistry; laser microdissection; mass spectrometry–based proteomics; onconephrology