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Proteomic Analysis for the Diagnosis of Fibrinogen Aα-Chain Amyloidosis

Taylor, GW; Gilbertson, JA; Sayed, R; Blanco, A; Rendell, NB; Rowczenio, D; Rezk, T; ... Gillmore, JD; + view all (2019) Proteomic Analysis for the Diagnosis of Fibrinogen Aα-Chain Amyloidosis. Kidney International Reports 10.1016/j.ekir.2019.04.007. (In press). Green open access

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Abstract

INTRODUCTION: Hereditary fibrinogen Aα-chain (AFib) amyloidosis is a relatively uncommon renal disease associated with a small number of pathogenic fibrinogen Aα (FibA) variants; wild-type FibA normally does not result in amyloid deposition. Proteomics is now routinely used to identify the amyloid type in clinical samples, and we report here our algorithm for identification of FibA in amyloid. METHODS: Proteomics data from 1001 Congo red–positive patient samples were examined using the Mascot search engine to interrogate the Swiss-Prot database and generate protein identity scores. An algorithm was applied to identify FibA as the amyloid protein based on Mascot scores. FibA variants were identified by appending the known amyloidogenic variant sequences to the Swiss-Prot database. RESULTS: AFib amyloid was identified by proteomics in 64 renal samples based on the Mascot scores relative to other amyloid proteins, the presence of a pathogenic variant, and coverage of the p.449-621 sequence. Contamination by blood could be excluded from a comparison of the FibA score with that of the fibrinogen β and γ chains. The proteomics results were consistent with the clinical diagnosis. Four additional renal samples did not fulfill all the criteria using the algorithm but were adjudged as AFib amyloid based on a full assessment of the clinical and biochemical results. CONCLUSION: AFib amyloid can be identified reliably in glomerular amyloid by proteomics using a score-based algorithm. Proteomics data should be used as a guide to AFib diagnosis, with the results considered together with all available clinical and laboratory information.

Type: Article
Title: Proteomic Analysis for the Diagnosis of Fibrinogen Aα-Chain Amyloidosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ekir.2019.04.007
Publisher version: https://doi.org/10.1016/j.ekir.2019.04.007
Language: English
Additional information: © 2019 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: amyloid, amyloidosis, fibrinogen, mass spectrometry, proteomics
UCL classification: UCL
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10076714
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