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

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%), Ab2M (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.