TY - JOUR
T1 - Amyloid Typing by Mass Spectrometry in Clinical Practice
T2 - a Comprehensive Review of 16,175 Samples
AU - Dasari, Surendra
AU - Theis, Jason D.
AU - Vrana, Julie A.
AU - Rech, Karen L.
AU - Dao, Linda N.
AU - Howard, Matthew T.
AU - Dispenzieri, Angela
AU - Gertz, Morie A.
AU - Hasadsri, Linda
AU - Highsmith, W. Edward
AU - Kurtin, Paul J.
AU - McPhail, Ellen D.
N1 - Publisher Copyright:
© 2020 Mayo Foundation for Medical Education and Research
PY - 2020/9
Y1 - 2020/9
N2 - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
AB - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
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U2 - 10.1016/j.mayocp.2020.06.029
DO - 10.1016/j.mayocp.2020.06.029
M3 - Article
C2 - 32861330
AN - SCOPUS:85089796349
SN - 0025-6196
VL - 95
SP - 1852
EP - 1864
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 9
ER -