Dataset Information

Subtyping of cardiac amyloidosis by mass spectrometry-based proteomics of endomyocardial biopsies

ABSTRACT: Cardiac amyloidosis is a severe clinical condition leading to restrictive cardiomyopathy and heart failure. With increasing options for specific treatment of different cardiac amyloid diseases, correct amyloid subtyping is essential for clinical outcome. Mass spectrometry-based methods for cardiac amyloid subtyping have become important diagnostic tools but are currently used only in a few reference laboratories. Such methods typically include laser-capture microdissection to ensure the specific analysis of amyloid deposits. While this strategy effectively reduces background signals, it is a labor-intensive and costly procedure hampering the implementation of these methods into a wider group of laboratories. Here we introduce a more direct proteomics-based method for subtyping of cardiac amyloids. Endomyocardial biopsies were retrospectively analyzed from fresh frozen material of 78 patients with cardiac amyloidosis and from 12 biopsies of unused donor heart explants. Cryostat sections were directly digested with trypsin and analyzed with the nano-liquid chromatography (nLC-MS/MS), and the data were evaluated by a proteomic software. With a diagnostic threshold set to 70% for each of the four most common amyloid proteins affecting the heart (LC k, LC l, TTR and SAA), 65 of the cases (87%) could be diagnosed, and of these, 61 cases (94%) were in concordance with the original diagnoses. The specimens were also analyzed for the summed intensities of the amyloid signature proteins (ApoE, ApoA-IV and SAP). The summed intensities were significantly higher (p<0.001) for all assigned amyloid cases, whereas unassigned cases were not significantly different from controls and had lower signals than the assigned cases (p<0.001), suggesting that signature proteins can serve as in situ quality markers of cardiac amyloid deposits. We argue that this efficient workflow can be useful for disseminating proteomics for cardiac amyloid subtyping into accredited clinical laboratories.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Proteomics Core Facility

LAB HEAD: Carina Sihlbom

PROVIDER: PXD033168 | Pride | 2022-10-27

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	3284_AllSamples_Inj123_Sprot_0mc_Percolator_AllQuan_QEHF-_1_.pdResult	Other
	3284_AllSamples_Inj1ONLY_Sprot_0mc_Percolator_QEHF.msf	Msf
	3284_AllSamples_Inj2ONLY_Sprot_0mc_Percolator_QEHF.msf	Msf
	3284_AllSamples_Inj3ONLY_Sprot_0mc_Percolator_QEHF.msf	Msf
	3347_LFQ_Inj123_0mc_AllQuan_QEHF_200403_04_601.pdResult	Other

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Publications

Subtyping of cardiac amyloidosis by mass spectrometry-based proteomics of endomyocardial biopsies.

Noborn Fredrik F Thomsen Christer C Vorontsov Egor E Bobbio Emanuele E Sihlbom Carina C Nilsson Jonas J Polte Christian L CL Bollano Entela E Vukusic Kristina K Sandstedt Joakim J Dellgren Göran G Karason Kristjan K Oldfors Anders A Larson Göran G

Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 20221009 1

<h4>Background</h4>Cardiac amyloidosis is a severe condition leading to restrictive cardiomyopathy and heart failure. Mass spectrometry-based methods for cardiac amyloid subtyping have become important diagnostic tools but are currently used only in a few reference laboratories. Such methods include laser-capture microdissection to ensure the specific analysis of amyloid deposits. Here we introduce a direct proteomics-based method for subtyping of cardiac amyloidosis.<h4>Methods</h4>Endomyocardi ...[more]

PMID: 36209425

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