Systemic amyloidoses and proteomics: The state of the art

Lavatelli, Francesca; Fonzo, Andrea Di; Palladini, Giovanni; Merlini, Giampaolo

doi:10.1016/j.euprot.2016.02.003

Cited by 21 publications

(33 citation statements)

References 90 publications

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“…While immunofluorescence in frozen sections and immunohistochemistry in paraffin sections have traditionally been used for amyloid typing, mass spectrometry has emerged as the method of choice for the typing of amyloid proteins, in particular in paraffin sections [6][7][8][9][10][11][12][62][63][64][65][66][67][68][69][70][71][72].…”

Section: Amyloid Typingmentioning

confidence: 99%

“…The rationale for the application of proteomics to amyloid typing lies in the relative abundance of amyloid protein in the tissue, where, usually, amyloid protein is the dominant protein [64][65][66]. Thus, the diagnosis of amyloid by proteomic methods is based on the presence of large spectra numbers for the amyloidogenic protein in conjunction with apolipoprotein E and serum amyloid P component (also known as "amyloid signature").…”

Section: Amyloid Typingmentioning

confidence: 99%

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The Pathology of Amyloidosis in Classification: A Review

2020

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Background: The amyloidoses are a rare and heterogeneous group of disorders that are characterized by the deposition of abnormally folded proteins in tissues ultimately leading to organ damage. The deposits are mainly extracellular and are recognizable by their affinity for Congo red and their yellow-green birefringence under polarized light. Current classification of amyloid in medical practice is based on the amyloid protein type. To date, 36 proteins have been identified as being amyloidogenic in humans. Summary: in clinical practice, it is critical to distinguish between treatable versus non-treatable amyloidoses. Moreover, amyloidoses with a genetic component must be distinguished from the sporadic types and systemic amyloidoses must be distinguished from the localized forms. Among the systemic amyloidoses, AL continues to be the most common amyloid diagnosis in the developed world; other clinically significant types include AA, ALECT2, and ATTR. The latter is emerging as an underdiagnosed type in both the hereditary and wild-type setting. Other hereditary amyloidoses include AFib, several amyloidoses derived from apolipoproteins, AGel, ALys, etc. In a dialysis setting, systemic amyloid derived from β 2 microglobulin (Aβ2M) should be considered, although a very rare hereditary variant has also been reported; several amyloido-ses may be typically associated with aging and several iatrogenic types have also emerged. Determination of the amyloid protein type is imperative before specific therapy can be implemented and the current methods are briefly summarized. A brief overview of the target organ involvement by amyloid type is also included. Key Messages: (1) Early diagnosis of amyloidosis continues to pose a significant challenge and requires the participation of many clinical and laboratory specialties. (2) Determination of the protein type is imperative before specific therapy can be implemented. (3) While 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. (4) While the spectrum of amyloidoses continues to expand, it is critical to distinguish between those that are currently treatable versus those that are untreatable and avoid causing harm by inappropriate treatment.

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Section: Amyloid Typingmentioning

confidence: 99%

Section: Amyloid Typingmentioning

confidence: 99%

The Pathology of Amyloidosis in Classification: A Review

2020

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“…Meanwhile, the mass spectrometry analysis of the bladder biopsy specimen confirmed wild-type transthyretin (ATTRwt) consistent with senile systemic amyloidosis. Immunohistochemical analysis was not performed as mass spectrometry has been demonstrated to be a wellvalidated technique to diagnose and classify amyloidosis [3,4]. Genetic testing can help clarify if the disease was hereditary or not but was not performed in this case and remains a limitation.…”

Section: Case Reportmentioning

confidence: 99%

Senile Systemic Amyloidosis Presenting as Hematuria: A Rare Presentation and Review of Literature

Jayakrishnan

Kamran

Shah

et al. 2020

Case Reports in Medicine

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Introduction. Senile systemic amyloidosis is a multisystem disease where wild-type insoluble transthyretin (ATTRwt) protein gets deposited in the tissues leading to organ dysfunction. Methodology. We present the case of a patient who presented with hematuria and bladder involvement by ATTRwt amyloidosis who ultimately died of multiorgan failure. Results. The patient was an 82-year-old white male with a history of ischemic cardiomyopathy (ejection fraction (EF): 20–25%), chronic atrial fibrillation, chronic kidney disease (CKD), and carpal tunnel syndrome who presented with acute hematuria, urinary retention, and progressive fatigue. He underwent cystoscopy and bladder biopsy which was positive on congo-red stain diagnostic for amyloidosis. Echocardiogram demonstrated worsening of EF to 10–15% and concentric left ventricle hypertrophy. MRI was not performed due to underlying CKD. His condition deteriorated during the hospital stay, and he developed cardiogenic shock and progressive liver dysfunction. Infectious workup was negative. Meanwhile, the biochemical investigations (serum protein electrophoresis, immunofixation, and urine kappa/lambda chains) ruled out plasma cell dyscrasias. Mass spectrometry analysis of the bladder biopsy specimen confirmed wild-type transthyretin (ATTRwt) amyloidosis consistent with senile systemic amyloidosis. Due to patients’ extremely poor prognosis, his family wished to focus on patient’s comfort-oriented measures only, and patient passed away shortly thereafter. Conclusion. Senile systemic amyloidosis can rarely present in an atypical fashion such as hematuria. The treatment options are limited in this disease process. Novel therapies are in the early phases of development. Concern also exists that in patients with multiple comorbidities, this entity is under recognized until the more advanced stages.

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“…Clearly, errors or delays in the diagnostic phase can translate into potentially dramatic consequences, due to wrong treatment choices or missed therapeutic opportunities. In recent years, proteomics has been introduced as a clinically useful tool for the management of amyloidoses [2,4,5]. In a short time since its first applications, it has gained impressive relevance as a method for amyloid protein identification without the use of antibodies, which are sometimes unreliable in this context [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, proteomics has been introduced as a clinically useful tool for the management of amyloidoses [2,4,5]. In a short time since its first applications, it has gained impressive relevance as a method for amyloid protein identification without the use of antibodies, which are sometimes unreliable in this context [5,6]. Methods for analyzing the whole-tissue proteome, especially in the case of fat tissue, or the amyloid deposits isolated by laser microdissection have been developed [4,5,[7][8][9].…”

Section: Introductionmentioning

confidence: 99%