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

Area of Science:

• Biochemistry
• Proteomics
• Clinical Diagnostics

Background:

• Amyloidosis is a group of diseases caused by protein misfolding and deposition.
• Accurate typing of amyloid is crucial for diagnosis and treatment.
• Mass spectrometry-based shotgun proteomics offers an unbiased method for amyloid identification.

Purpose of the Study:

• To map the occurrence and distribution of various amyloid types in a large clinical cohort.
• To establish an organ-by-type map for 21 identified amyloid types.
• To characterize the organ tropism of rare amyloid types.

Main Methods:

• Implementation of a mass spectrometry-based shotgun proteomics assay in a central laboratory.
• Analysis of 16,175 amyloidosis specimens over an 11-year period (2008-2018).
• Development of a modified bioinformatics pipeline for detecting amino acid substitutions in hereditary amyloidosis.

Main Results:

• Identification of 21 distinct amyloid types, with AL amyloidosis (59.0%) and ATTR amyloidosis (28.4%) being the most prevalent.
• Creation of the first comprehensive organ-by-type map for 21 amyloid types across 31 organs.
• Detailed mapping of organ tropism for 18 rare amyloid types.
• Achieved 100% specificity in detecting amino acid substitutions in hereditary amyloidosis cases.

Conclusions:

• Proteomics-based amyloid typing is an effective, single-assay method for identifying all amyloid types.
• This approach optimally supports the diagnosis and treatment of amyloidosis patients in clinical practice.
• The developed organ-by-type maps provide valuable insights into disease patterns and organ involvement.