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Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre

  • Diana Canetti EMAIL logo , Nigel B. Rendell , Janet A. Gilbertson , Nicola Botcher , Paola Nocerino , Angel Blanco , Lucia Di Vagno , Dorota Rowczenio , Guglielmo Verona , P. Patrizia Mangione , Vittorio Bellotti , Philip N. Hawkins , Julian D. Gillmore und Graham W. Taylor
Veröffentlicht/Copyright: 18. Februar 2020
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 58 Heft 6

Abstract

Systemic amyloidosis is a serious disease which is caused when normal circulating proteins misfold and aggregate extracellularly as insoluble fibrillary deposits throughout the body. This commonly results in cardiac, renal and neurological damage. The tissue target, progression and outcome of the disease depends on the type of protein forming the fibril deposit, and its correct identification is central to determining therapy. Proteomics is now used routinely in our centre to type amyloid; over the past 7 years we have examined over 2000 clinical samples. Proteomics results are linked directly to our patient database using a simple algorithm to automatically highlight the most likely amyloidogenic protein. Whilst the approach has proved very successful, we have encountered a number of challenges, including poor sample recovery, limited enzymatic digestion, the presence of multiple amyloidogenic proteins and the identification of pathogenic variants. Our proteomics procedures and approaches to resolving difficult issues are outlined.

Keywords: amyloidosis; laser capture dissection; proteomics
Corresponding author: Dr. Diana Canetti, Wolfson Drug Discovery Unit and National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK, Phone: +44 (0)207 433 2824

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The UK National Amyloidosis Centre is funded by NHS England. Core support for the Wolfson Drug Discovery Unit is provided by the UK National Institute for Health Research Biomedical Research Centre and Unit Funding scheme via the UCLH/UCL Biomedical Research Centre. Funding for the proteomics platform was generously provided by the Wolfson Foundation, Funder Id: http://dx.doi.org/10.13039/501100001320, Grant Number: PR/YLR/NW/20885 and the UCL Amyloidosis Research Fund.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  6. Ethical approval: All patients were managed in accordance with the Declaration of Helsinki and informed consent for use of material and publication of data was obtained.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-1007).

Received: 2019-09-30
Accepted: 2020-01-16
Published Online: 2020-02-18
Published in Print: 2020-06-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Advancements in mass spectrometry as a tool for clinical analysis: part II
  4. Quantitative protein assessment
  5. Complexity, cost, and content – three important factors for translation of clinical protein mass spectrometry tests, and the case for apolipoprotein C-III proteoform testing
  6. Vedolizumab quantitation using high-resolution accurate mass-mass spectrometry middle-up protein subunit: method validation
  7. Development and evaluation of an element-tagged immunoassay coupled with inductively coupled plasma mass spectrometry detection: can we apply the new assay in the clinical laboratory?
  8. MALDI-MS for the clinic
  9. Matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS): basics and clinical applications
  10. Clinical use of mass spectrometry (imaging) for hard tissue analysis in abnormal fracture healing
  11. Cellular resolution in clinical MALDI mass spectrometry imaging: the latest advancements and current challenges
  12. Bacterial identification by lipid profiling using liquid atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry
  13. Clinical application of ’omics technologies
  14. Individualized metabolomics: opportunities and challenges
  15. Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre
  16. The “olfactory fingerprint”: can diagnostics be improved by combining canine and digital noses?
  17. Peptidomic and proteomic analysis of stool for diagnosing IBD and deciphering disease pathogenesis
  18. The influence of hypoxia on the prostate cancer proteome
  19. Laboratory automation and kit-based approaches
  20. Mass spectrometry and total laboratory automation: opportunities and drawbacks
  21. The pathway through LC-MS method development: in-house or ready-to-use kit-based methods?
  22. Evaluation of the 25-hydroxy vitamin D assay on a fully automated liquid chromatography mass spectrometry system, the Thermo Scientific Cascadion SM Clinical Analyzer with the Cascadion 25-hydroxy vitamin D assay in a routine clinical laboratory
https://doi.org/10.1515/cclm-2019-1007
Schlagwörter für diesen Artikel
amyloidosis; laser capture dissection; proteomics

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Advancements in mass spectrometry as a tool for clinical analysis: part II
  4. Quantitative protein assessment
  5. Complexity, cost, and content – three important factors for translation of clinical protein mass spectrometry tests, and the case for apolipoprotein C-III proteoform testing
  6. Vedolizumab quantitation using high-resolution accurate mass-mass spectrometry middle-up protein subunit: method validation
  7. Development and evaluation of an element-tagged immunoassay coupled with inductively coupled plasma mass spectrometry detection: can we apply the new assay in the clinical laboratory?
  8. MALDI-MS for the clinic
  9. Matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS): basics and clinical applications
  10. Clinical use of mass spectrometry (imaging) for hard tissue analysis in abnormal fracture healing
  11. Cellular resolution in clinical MALDI mass spectrometry imaging: the latest advancements and current challenges
  12. Bacterial identification by lipid profiling using liquid atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry
  13. Clinical application of ’omics technologies
  14. Individualized metabolomics: opportunities and challenges
  15. Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre
  16. The “olfactory fingerprint”: can diagnostics be improved by combining canine and digital noses?
  17. Peptidomic and proteomic analysis of stool for diagnosing IBD and deciphering disease pathogenesis
  18. The influence of hypoxia on the prostate cancer proteome
  19. Laboratory automation and kit-based approaches
  20. Mass spectrometry and total laboratory automation: opportunities and drawbacks
  21. The pathway through LC-MS method development: in-house or ready-to-use kit-based methods?
  22. Evaluation of the 25-hydroxy vitamin D assay on a fully automated liquid chromatography mass spectrometry system, the Thermo Scientific Cascadion SM Clinical Analyzer with the Cascadion 25-hydroxy vitamin D assay in a routine clinical laboratory
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