Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis

Hazenberg, Bouke P. C.; Bijzet, Johan; Limburg, Pieter C.; Skinner, Martha; Hawkins, Philip N.; Butrimienė, İrena; Livneh, Avi; Lesnyak, Olga; Nasonov, Evgeney L; Filipowicz-Sosnowska, Anna; Gül, Ahmet; Merlini, Giampaolo; Wiland, Piotr; Özdoğan, Huri; Gorevic, Peter D.; Maı̈z, H. Ben; Benson, Merrill D.; Direşkeneli, Haner; Kaarela, K.; Garceau, D.; Hauck, W.; Rijswijk, M.H. van

doi:10.1080/13506120701260224

Cited by 35 publications

(27 citation statements)

References 24 publications

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“…13 All patients' samples had Congo red positivity score more than or equal to 3ϩ. 11 Proteins were extracted from tissue as described, 7 dialyzed against 50mM ammonium bicarbonate (18 hours, 4°C), and digested with trypsin. Resulting peptide mixtures were analyzed in 2 replicates by MudPIT, based on 2-dimensional chromatography coupled to tandem MS. 14 The software MAProMa 14,15 was used to identify up-represented proteins in patients and select those forming There is an Inside Blood commentary on this article in this issue.…”

Section: Methodsmentioning

confidence: 99%

Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue

Brambilla

Lavatelli²,

Silvestre

et al. 2012

Blood

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Section: Methodsmentioning

confidence: 99%

Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue

Brambilla

Lavatelli²,

Silvestre

et al. 2012

Blood

Self Cite

168

153

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show abstract

“…A validated semi-quantitative grading system was used ranging from 0 to 4+: 0 (negative), 1+ (minute, <1% of surface area), 2+ (little, between 1% and 10%), 3+ (moderate, between 10-60%), and 4+ (abundant, >60%). 3 In case of disagreement between the 2 observers, the 3 smears were reviewed and discussed to obtain consensus. All fat smears were assessed in a blinded manner for clinical and laboratory data.…”

Section: Amyloid Deposition In Fat Tissuementioning

confidence: 99%

“…Subcutaneous abdominal fat tissue is the preferential biopsy site, because of the convenient and non-invasive character and excellent diagnostic accuracy. 2 The validated semi-quantitative assessment of amyloid in fat tissue 3 provides the opportunity to monitor severity of amyloid deposition in tissue during follow-up.…”

Section: Introductionmentioning

confidence: 99%

Histological regression of amyloid in AL amyloidosis is exclusively seen after normalization of serum free light chain

Gameren¹,

Rijswijk²,

Bijzet³

et al. 2009

Haematologica

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“…[10][11][12][13][14][15][16][17][18][19] We and others have shown the possibility of applying proteomic approaches including MS-based proteomics for typing amyloidosis in SFA specimens in a research setting. [20][21][22][23][24][25] In this study, we show the clinical validation and implementation of an MS-based proteomic assay for the diagnosis and typing of amyloidosis in SFA specimens in a 1988 Clinical Laboratory Improvement Amendments (CLIA) accredited laboratory setting. The assay not only provides diagnostic information but in many cases also sheds light on the underlying pathogenesis by identifying the detailed proteome of the amyloid deposits.…”

Section: Introductionmentioning

confidence: 99%

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Vrana¹,

Theis²,

Dasari³

et al. 2014

Haematologica

152

111

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Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis.Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics ABSTRACT Subcutaneous fat aspiration for diagnosis of systemic amyloidosisSpecimens were obtained, stained with Congo red and interpreted according to previously established protocols described elsewhere.5 For the validation cohort one half of each specimen was used to make a smear and stained with Congo red. The other half, irrespective of whether the smear was positive for amyloid by Congo red, was processed for MS-based proteomic analysis. For the clinical cohort, one half of each specimen was used to make a smear and stained with Congo red. The other half was processed for MS-based proteomic analysis only if the first half stained positive for amyloidosis, as required by the established clinical practice and test validation criteria. Mass spectrometry-based proteomic analysis of subcutaneous fat aspiratesThe SFA specimens were processed for MS analysis using a modification of a previously established protocol.26 Briefly, the aspirate was solubilized and digested in trypsin and used for protein identification by nano-flow liquid chromatography electrospray tandem MS.9 Peptide spectra present in the raw data files were matched against a composite protein sequence database using three different search engines (Sequest Measurement of serum immunoglobulin free light chainsSerum immunoglobulin ...

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Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis

Cited by 35 publications

References 24 publications

Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue

Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue

Histological regression of amyloid in AL amyloidosis is exclusively seen after normalization of serum free light chain

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

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