Conti, M;
Poppi, I;
Cavedagna, TM;
Zamagni, E;
Leone, O;
Corti, B;
Milandri, A;
... Rapezzi, C; + view all
(2018)
A targeted proteomics approach to amyloidosis typing.
Clinical Mass Spectrometry
, 7
pp. 18-28.
10.1016/j.clinms.2018.02.001.
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Abstract
Background: Amyloidosis is a life threatening disease caused by deposition of various types of blood serum proteins in organs and tissues. Knowing the type of protein involved is the basis of a correct diagnosis and personalized medical treatment. While the classical approach uses immunohistochemistry, in recent years, laser micro-dissection, followed by high resolution LC-MS/MS, has been shown to provide superior diagnostic sensitivity and specificity. This techniques, however, is only available at major reference proteomics centers. // Objective: To perform clinical amyloid protein typing using low-resolution mass spectrometry and no laser micro dissection (LMD), we developed a targeted proteomics approach for the determination of both frequently encountered amyloid proteins (i.e., κ and -λ immunoglobulin light chains and transthyretin (TTR)) and specific reference proteins (i.e., actin (A) for cardiac muscle tissue, or fatty acid binding protein 4 (FBP4) for subcutaneous adipose tissue) in histologic specimens. // Method: Small tissue fragments and/or histological sections were digested to yield a protein mixture that was subsequently reduced, alkylated and trypsinized to obtain a peptide mixture. After SPE purification and LC separation, proteotypic peptides were detected by their MRM transitions. // Results: The method showed high specificity and sensitivity for amyloid protein proteotypic peptides. LODs were 1.0, 0.1, 0.2 picomoles in cardiac muscle tissue (CMT) and 0.1, 0.2, 0.5 picomoles in subcutaneous adipose tissue (SAT) for TTR, κ-, and λ-LC proteins, respectively. Amyloid to tissue-specific protein signal ratios correlated with the presence of amyloid deposits in clinical samples. // Conclusions: This targeted proteomics approach enables sensitive and specific discrimination of amyloidosis affected tissues for the purpose of clinical research.
| Type: | Article |
|---|---|
| Title: | A targeted proteomics approach to amyloidosis typing |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.clinms.2018.02.001 |
| Publisher version: | https://doi.org/10.1016/j.clinms.2018.02.001 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | amyloidosis, subcutaneous adipose tissue, cardiac muscle tissue, protein typing, targeted proteomics, mass spectrometry, transthyretin, immunoglobulin light chains |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10054612 |
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