Amyloid Typing by Mass Spectrometry in Clinical Practice: a Comprehensive Review of 16,175 Samples

• Published in: Mayo Clinic proceedings Vol. 95; no. 9; pp. 1852 - 1864
• Main Authors: Dasari, Surendra, Theis, Jason D., Vrana, Julie A., Rech, Karen L., Dao, Linda N., Howard, Matthew T., Dispenzieri, Angela, Gertz, Morie A., Hasadsri, Linda, Highsmith, W. Edward, Kurtin, Paul J., McPhail, Ellen D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.09.2020; Elsevier, Inc; Frontline Medical Communications Inc; Elsevier Limited
• Subjects: Amino Acid Sequence; Amino acids; Amyloid - classification; Amyloid - metabolism; Amyloidosis; Amyloidosis - diagnosis; Amyloidosis - metabolism; Antibodies; Apolipoproteins; Bioinformatics; Biopsy; Bone marrow; Chromatography; Clinical medicine; Female; Humans; Identification; Laboratories; Male; Mass Spectrometry; Mass spectroscopy; Methods; Microscopy; Mutation; Patients; Peptides; Proteins; Proteomics; Proteomics - instrumentation; Retrospective Studies; Scientific imaging; Search engines; Sex Distribution; Transforming growth factor-b1; Tropism; Typing; Massachusetts; LC-MS/MS; GI; OR; FFPE; IHC; LC; ATTRwt; ATTRv; CR; SFA
• ISSN: 0025-6196; 1942-5546
• DOI: 10.1016/j.mayocp.2020.06.029

To map the occurrence of amyloid types in a large clinical cohort using mass spectrometry-based shotgun proteomics, an unbiased method that unambiguously identifies all amyloid types in a single assay. A mass spectrometry-based shotgun proteomics assay was implemented in a central reference laboratory. We documented our experience of typing 16,175 amyloidosis specimens over an 11-year period from January 1, 2008, to December 31, 2018. We identified 21 established amyloid types, including AL (n=9542; 59.0%), ATTR (n=4600; 28.4%), ALECT2 (n=511; 3.2%), AA (n=463; 2.9%), AH (n=367; 2.3%), AIns (n=182; 1.2%), KRT5-14 (n=94; <1%), AFib (n=71; <1%), AApoAIV (n=57; <1%), AApoA1 (n=56; <1%), AANF (n=47; <1%), Aβ2M (n=38; <1%), ASem1 (n=34; <1%), AGel (n=29; <1%), TGFB1 (n=29; <1%), ALys (n=15; <1%), AIAPP (n=13; <1%), AApoCII (n=11; <1%), APro (n=8; <1%), AEnf (n=6; <1%), and ACal (n=2; <1%). We developed the first comprehensive organ-by-type map showing the relative frequency of 21 amyloid types in 31 different organs, and the first type-by-organ map showing organ tropism of 18 rare types. Using a modified bioinformatics pipeline, we detected amino acid substitutions in cases of hereditary amyloidosis with 100% specificity. Amyloid typing by proteomics, which effectively recognizes all amyloid types in a single assay, optimally supports the diagnosis and treatment of amyloidosis patients in routine clinical practice.