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

Publication date: Available online 21 June 2017
Source:Journal of Proteomics
Author(s): P. Patrizia Mangione, Giuseppe Mazza, Janet A. Gilbertson, Nigel B. Rendell, Diana Canetti, Sofia Giorgetti, Luca Frenguelli, Marco Curti, Tamer Rezk, Sara Raimondi, Mark B. Pepys, Philip N. Hawkins, Julian D. Gillmore, Graham W. Taylor, Massimo Pinzani, Vittorio Bellotti
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.SignificanceUnequivocal 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.

Graphical abstract

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