Proteomics Fundamentally Advance the Diagnosis and Management of Amyloidosis

Lavatelli, Francesca; Merlini, Giampaolo

doi:10.1016/j.mayocp.2020.07.013

Cited by 3 publications

(5 citation statements)

References 10 publications

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“…This type of analysis is routinely performed in major amyloid centers, and proteomic data from thousands of AL cases are now available [16,18,20,61,62,80,81]. Proteomic typing offers important advantages that have been extensively reviewed elsewhere [61,82]; however, AL amyloidosis also poses unique challenges to this approach. In fact, the above-discussed uniqueness of sequence in the V L translates in the fact that protein databases cannot contain the full sequence of each monoclonal LC, and therefore peptide ions from the variable domain, which forms the structured core of the fibrils, may not be matched [21,28,83].…”

Section: The Al Amyloid Proteome: Disease Typing Characterization Of Deposited Lc Proteoforms and The Amyloid Environmentmentioning

confidence: 99%

Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

et al. 2021

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Amyloidoses are characterized by aggregation of proteins into highly ordered amyloid fibrils, which deposit in the extracellular space of tissues, leading to organ dysfunction. In AL (amyloid light chain) amyloidosis, the most common form in Western countries, the amyloidogenic precursor is a misfolding-prone immunoglobulin light chain (LC), which, in the systemic form, is produced in excess by a plasma cell clone and transported to target organs though blood. Due to the primary role that proteins play in the pathogenesis of amyloidoses, mass spectrometry (MS)-based proteomic studies have gained an established position in the clinical management and research of these diseases. In AL amyloidosis, in particular, proteomics has provided important contributions for characterizing the precursor light chain, the composition of the amyloid deposits and the mechanisms of proteotoxicity in target organ cells and experimental models of disease. This review will provide an overview of the major achievements of proteomic studies in AL amyloidosis, with a presentation of the most recent acquisitions and a critical discussion of open issues and ongoing trends.

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Section: The Al Amyloid Proteome: Disease Typing Characterization Of Deposited Lc Proteoforms and The Amyloid Environmentmentioning

confidence: 99%

Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

et al. 2021

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“…Although, in general, proteomics has become a very successful method for amyloid protein typing, with high sensitivity and specificity in formalinfixed, paraffin-embedded tissues, there are also important limitations [38][39][40][41][42]. Thus, low abundance proteins/small deposits may be difficult to capture and various preanalytical factors (quality of samples, blood contamination) as well as occasional detection of more than one amyloidogenic protein can make amyloid protein identification challenging.…”

Section: Amyloid Types: Diversity Versus the Most Common Types And Es...mentioning

confidence: 99%

“…Recently, quantitative analyses of amyloid proteins in clinical specimens, formalin-fixed, paraffin-embedded (FFPE) tissues, was reported using mass spectrometry based quantification by isotope-labelled cell-free products (MS-QBIC) [41]. Although further discussion on this topic is beyond the scope of this review, additional information can be found in several recently published articles on the subject [38][39][40][41][42].…”

Section: Amyloid Types: Diversity Versus the Most Common Types And Es...mentioning

confidence: 99%

“…Amyloid protein type diagnosis can be based on immune stains or proteomic methods [5,14 ▪▪ ,15 ▪ ,36–42]. Although, in recent years, a significant proportion of specimens, at least in the USA, has been tested using mass spectrometry, immunofluorescence on frozen sections is still used as a first-line approach in amyloid typing in many laboratories [3 ▪ ,36,37].…”

Section: Amyloid Protein Typing In Contemporary Clinical Practicementioning

confidence: 99%

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Diagnosis of amyloid beyond Congo red

Picken

2020

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Amyloidoses are a group of rare and heterogeneous diseases in which abnormally folded proteins deposit in tissues and lead to organ damage. A brief review of advances in the diagnosis of extracerebral systemic amyloidoses in the context of recent advances in their clinical management is provided. Recent findings Although steady progress in the treatment of AL and AA has evolved over many years, significant advances in the treatment of ATTR, transthyretin-derived amyloidosis, have been achieved only recently. This coincides with the emergence of nontissue diagnosis of cardiac ATTR in both the hereditary and wild-type settings. The latter is emerging as possibly the most prevalent type of systemic amyloidosis. Available treatments are amyloid protein type dependent and, hence, following amyloid detection, amyloid protein typing is necessary. Although mass spectrometry has emerged as the preferred method of amyloid typing, careful application of immune methods is still clinically useful but caution and experience, as well as awareness of the limitations of each method, are necessary in their interpretation. Summary Despite significant advances in the treatment of the systemic amyloidoses, outcomes remain poor, primarily due to delays in diagnosis. Precise diagnosis of the amyloid protein type is critical for treatment selection.

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“…Proteomics has revolutionized the field of amyloid diagnosis, which is considered to be the new gold standard approach for disease typing. Proteomics now has a profound impact in the clinical management of amyloid diseases [ 23 ]. However, until now, there is not a traditional FFPE-based proteomics and bioinformatics analysis used for the subtype of renal amyloidosis.…”

Section: Introductionmentioning

confidence: 99%

A Pilot Study of Rare Renal Amyloidosis Based on FFPE Proteomics

Meng

Xia

et al. 2021

Molecules

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Renal amyloidosis typically manifests albuminuria, nephrotic-range proteinuria, and ultimately progresses to end-stage renal failure if diagnosed late. Different types of renal amyloidosis have completely different treatments and outcomes. Therefore, amyloidosis typing is essential for disease prognosis, genetic counseling and treatment. Thirty-six distinct proteins currently known to cause amyloidosis that have been described as amyloidogenic precursors, immunohistochemistry (IHC) or immunofluorescence (IF), can be challenging for amyloidosis typing especially in rare or hereditary amyloidosis in clinical practice. We made a pilot study that optimized the proteomics pre-processing procedures for trace renal amyloidosis formalin-fixed paraffin-embedded (FFPE) tissue samples, combined with statistical and bioinformatics analysis to screen out the amyloidosis-related proteins to accurately type or subtype renal amyloidosis in order to achieve individual treatment. A sensitive, specific and reliable FFPE-based proteomics analysis for trace sample manipulation was developed for amyloidosis typing. Our results not only underlined the great promise of traditional proteomics and bioinformatics analysis using FFPE tissues for amyloidosis typing, but also proved that retrospective diagnosis and analysis of previous cases laid a solid foundation for personalized treatment.

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Proteomics Fundamentally Advance the Diagnosis and Management of Amyloidosis

Cited by 3 publications

References 10 publications

Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

Diagnosis of amyloid beyond Congo red

A Pilot Study of Rare Renal Amyloidosis Based on FFPE Proteomics

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