Increasing the accuracy of proteomic typing by decellularisation of amyloid tissue biopsies

J Proteomics. 2017 Aug 8;165:113-118. doi: 10.1016/j.jprot.2017.06.016. Epub 2017 Jun 21.

Abstract

Diagnosis and treatment of systemic amyloidosis depend on accurate identification of the specific amyloid fibril protein forming the tissue deposits. Confirmation of monoclonal immunoglobulin light chain amyloidosis (AL), requiring cytotoxic chemotherapy, and avoidance of such treatment in non-AL amyloidosis, are particularly important. Proteomic analysis characterises amyloid proteins directly. It complements immunohistochemical staining of amyloid to identify fibril proteins and gene sequencing to identify mutations in the fibril precursors. However, proteomics sometimes detects more than one potentially amyloidogenic protein, especially immunoglobulins and transthyretin which are abundant plasma proteins. Ambiguous results are most challenging in the elderly as both AL and transthyretin (ATTR) amyloidosis are usually present in this group. We have lately described a procedure for tissue decellularisation which retains the structure, integrity and composition of amyloid but removes proteins that are not integrated within the deposits. Here we show that use of this procedure before proteomic analysis eliminates ambiguity and improves diagnostic accuracy.

Significance: Unequivocal identification of the protein causing amyloidosis disease is crucial for correct diagnosis and treatment. As a proof of principle, we selected a number of cardiac and fat tissue biopsies from patients with various types of amyloidosis and show that a classical procedure of decellularisation enhances the specificity of the identification of the culprit protein reducing ambiguity and the risk of misdiagnosis.

Keywords: Amyloid typing; Amyloidosis; Decellularisation; Proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry
  • Adipose Tissue / pathology
  • Amyloid / chemistry*
  • Amyloidosis / diagnosis
  • Amyloidosis / pathology
  • Biopsy
  • Cell-Free System
  • Humans
  • Immunoglobulin Light Chains
  • Myocardium / chemistry
  • Myocardium / pathology
  • Prealbumin
  • Proteomics / methods
  • Proteomics / standards*
  • Sensitivity and Specificity

Substances

  • Amyloid
  • Immunoglobulin Light Chains
  • Prealbumin