The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis

PLoS One. 2015 May 18;10(5):e0127180. doi: 10.1371/journal.pone.0127180. eCollection 2015.

Abstract

Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP) method that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration unit and can accelerate the digestion process with the assistance of a microwave. Additionally, two parameters (P- and D-scores) based on the exponentially modified protein abundance index were developed to define the existence of amyloid deposits and those causative proteins with the greatest abundance. Using our protocol, twenty cases of systemic amyloidosis that were well-typed according to clinical diagnostic standards (training group) and another twenty-four cases without subtype diagnoses (validation group) were analyzed. Using this approach, sample preparation could be completed within four hours. We successfully subtyped 100% of the cases in the training group, and the diagnostic success rate in the validation group was 91.7%. This maFASP-aided proteomic protocol represents an efficient approach for amyloid diagnosis and subtyping, particularly for serum-contaminated samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / classification*
  • Amyloidosis / diagnosis*
  • Analytic Sample Preparation Methods*
  • Biomarkers / metabolism
  • Case-Control Studies
  • Chromatography, Liquid / methods*
  • Filtration / instrumentation*
  • Hemoglobins / metabolism
  • Humans
  • Immunoglobulin Light-chain Amyloidosis
  • Microwaves*
  • Reproducibility of Results
  • Serum Albumin / metabolism
  • Tandem Mass Spectrometry / methods*

Substances

  • Amyloid
  • Biomarkers
  • Hemoglobins
  • Serum Albumin

Grants and funding

This work was funded by the National Nature Science Foundation of China (81370672, for Jian Li), Beijing Municipal Science & Technology Commission (Z131107002213050, for Jian Li), Peking Union Medical College New Star (2011, for Jian Li), and the National Public Health Grand Research Foundation (201202017, for Jian Li).