Amyloid Protein Identification, Paraffin, LC-MS/MS
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Amyloidosis is a group of hereditary and acquired diseases that are unified by extracellular tissue deposition of misfolded proteins resulting in end organ damage. Amyloidosis can be a systemic or localized disease. Although many cases of amyloidosis are hereditary, most are acquired as the result of an underlying monoclonal B-cell/plasma cell malignancy, as a phenomenon of aging, or as the result of long-standing chronic inflammation. Specific amyloid-related diseases are therefore associated with specific amyloid proteins. These include kappa or lambda immunoglobulin light chains (AL amyloid), transthyretin (ATTR amyloid), serum amyloid A (SAA amyloid), and other uncommon subtypes. Because treatment of amyloidosis patients differs radically for the different amyloid subtypes, it is critically important to accurately identify the proteins that constitute the amyloid deposits.
The basic diagnosis of amyloidosis is typically achieved by Congo red staining of paraffin-embedded tissue biopsy specimens obtained from diverse anatomic sites and demonstrating Congo red-positive, apple-green birefringent, amyloid deposits in the tissues. The next step is to definitively subtype the amyloid deposits. This test fulfills that need. It relies on laser microdissection of Congo red-positive amyloid deposits followed by analysis by liquid chromatography-tandem mass spectrometry to accurately determine the identity of the proteins that constitute the amyloid.
Definitive identification of amyloid proteins
An interpretation will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
No significant cautionary statements
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Theis JD, Dasari S, Vrana JA, et al: Shotgun-proteomics-based clinical testing for diagnosis and classification of amyloidosis. J Mass Spectrom 2013;48(10):1067-1077
2. Said SM, Sethi S, Valeri AM, et al: Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases. Clin J Am Soc Nephrol 2013 Sep;8(9):1515-1523
3. Dogan A: Chapter 21: Classification of amyloidosis by mass spectrometry-based proteomics. In Amyloid and Related Disorders: Surgical Pathology and Clinical Correlations. Edited by MM Picken, A Dogan, GA Herrera. First edition. New York, Springer Science, 2012, pp 261-272
4. Klein CJ, Vrana JA, Theis JD, et al: Amyloid neuropathy type is distinguished by mass spectrometric based proteomic analysis of nerve tissue. Arch Neurol 2011:68(2):195-199
5. Vrana JA, Gamez JD, Madden BJ, et al: Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 2009;114(24):4957-4959
The Amyloid Protein Identification test employs Liquid Tissue® sample preparation licensed from Expression Pathology Inc., Rockville MD, under U.S. Patent 7,473,532 and patents pending and foreign equivalents thereof.