Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · 2022
Subtyping of cardiac amyloidosis by mass spectrometry-based proteomics of endomyocardial biopsies.
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Noborn Fredrik, Thomsen Christer, Vorontsov Egor, Bobbio Emanuele, Sihlbom Carina, Nilsson Jonas, Polte Christian L, Bollano Entela, Vukusic Kristina, Sandstedt Joakim, Dellgren Göran, Karason Kristjan, Oldfors Anders, Larson Göran
Аннотация
BACKGROUND: 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.
METHODS: Endomyocardial biopsies were retrospectively analysed from fresh frozen material of 78 patients with cardiac amyloidosis and from 12 biopsies of unused donor heart explants. Cryostat sections were digested with trypsin and analysed with liquid chromatography - mass spectrometry, and data were evaluated by proteomic software.
RESULTS: With a diagnostic threshold set to 70% for each of the four most common amyloid proteins affecting the heart (LC κ, LC λ, 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 analysed for the summed intensities of the amyloid signature proteins (ApoE, ApoA-IV and SAP). The intensities were significantly higher (p < 0.001) for all assigned cases compared with controls.
CONCLUSION: Cardiac amyloidosis can be successfully subtyped without the prior enrichment of amyloid deposits with laser microdissection.
METHODS: Endomyocardial biopsies were retrospectively analysed from fresh frozen material of 78 patients with cardiac amyloidosis and from 12 biopsies of unused donor heart explants. Cryostat sections were digested with trypsin and analysed with liquid chromatography - mass spectrometry, and data were evaluated by proteomic software.
RESULTS: With a diagnostic threshold set to 70% for each of the four most common amyloid proteins affecting the heart (LC κ, LC λ, 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 analysed for the summed intensities of the amyloid signature proteins (ApoE, ApoA-IV and SAP). The intensities were significantly higher (p < 0.001) for all assigned cases compared with controls.
CONCLUSION: Cardiac amyloidosis can be successfully subtyped without the prior enrichment of amyloid deposits with laser microdissection.