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

Autor: Mangione PP; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK; Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Pavia, Italy., Mazza G; Institute for Liver and Digestive Health, University College London, London, UK., Gilbertson JA; National Amyloidosis Centre, University College London and Royal Free Hospital, London, UK., Rendell NB; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK., Canetti D; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK; Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Pavia, Italy; CEINGE and Department of Chemical Sciences, University of Naples, Naples, Italy., Giorgetti S; Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Pavia, Italy., Frenguelli L; Institute for Liver and Digestive Health, University College London, London, UK., Curti M; Institute for Liver and Digestive Health, University College London, London, UK., Rezk T; National Amyloidosis Centre, University College London and Royal Free Hospital, London, UK., Raimondi S; Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Pavia, Italy., Pepys MB; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK; National Amyloidosis Centre, University College London and Royal Free Hospital, London, UK., Hawkins PN; National Amyloidosis Centre, University College London and Royal Free Hospital, London, UK., Gillmore JD; National Amyloidosis Centre, University College London and Royal Free Hospital, London, UK., Taylor GW; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK., Pinzani M; Institute for Liver and Digestive Health, University College London, London, UK. Electronic address: m.pinzani@ucl.ac.uk., Bellotti V; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK; Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Pavia, Italy. Electronic address: v.bellotti@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2017 Aug 08; Vol. 165, pp. 113-118. Date of Electronic Publication: 2017 Jun 21.
DOI: 10.1016/j.jprot.2017.06.016
Abstrakt: 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.
(Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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