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

Brambilla, Francesca; Lavatelli, Francesca; Silvestre, Dario Di; Valentini, Veronica; Rossi, Rossana; Palladini, Giovanni; Obici, Laura; Verga, Laura; Mauri, Pierluigi; Merlini, Giampaolo

doi:10.1182/blood-2011-07-365510

Cited by 167 publications

(160 citation statements)

References 25 publications

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“…The amyloid deposits were characterized as AL-type by immunoelectron microscopy or proteomics in all cases. 34,35 Evidence of a monoclonal component of the same isotype of that identified in the amyloid fibrils at serum and urine immunofixation electrophoresis and/or an abnormal FLC κ/λ ratio was required. 36 Subjects with lytic bone lesions were excluded.…”

Section: Methodsmentioning

confidence: 99%

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

et al. 2014

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Oral melphalan and dexamethasone (MDex) is a standard treatment for patients with AL amyloidosis who are not eligible for stem cell transplantation at many referral centers. However, following encouraging reports on the activity of bortezomib combined with alkylators and dexamethasone, these combinations are being moved to frontline therapy. We compared the outcome of 87 patients treated with bortezomib plus MDex (BMDex) with that of 87 controls treated with MDex. Patients and controls were matched for age, cardiac and renal function and free light chain burden. A higher rate of complete responses was observed with BMDex (42 vs 19%), but this did not result in a survival improvement in the overall population. However, a significant survival advantage for BMDex was observed in patients without severe (New York Heart Association class III or IV) heart failure and with N-terminal pro-natriuretic peptide type-B <8500 ng/l. Patients treated with full-dose dexamethasone had similar response rates and survival whether they received bortezomib or not. Intermediate-risk patients who are not fit enough to receive high-dose dexamethasone are likely to take the greatest advantage from the addition of bortezomib to MDex.

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Section: Methodsmentioning

confidence: 99%

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

et al. 2014

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“…Moreover, the novel proteomic-based analyses of affected tissues have identified sets of tissue-resident (including extracellular matrix components, species involved in protein folding, and proteins implicated in energetic metabolism) and amyloid-associated proteins, whose representation changes in the presence of amyloid deposits [50][51][52]. If validated, these proteins, as single analytes or in combination, could represent novel, sensitive markers of amyloid deposition and indicators of amyloid-associated damage.…”

Section: Use Of Biomarkers For Early Diagnosismentioning

confidence: 99%

“…Despite the different etiology, however, the clinical presentation is not diriment: amyloid organ dysfunction is non-specific, and the same organ can be affected by different types of amyloidosis, with similar manifestations, but different clinical implications. The field of tissue amyloid typing has recently witnessed novel developments, the most important of which is the use of proteomics in clinical setting [51,52,[66][67][68][69]. Proteomics is now complementing the traditional histological techniques.…”

Section: Amyloidosis Typingmentioning

confidence: 99%

“…Several methods for amyloid proteomic typing have been proposed, which allow analysis of both paraffinembedded and fresh tissue [51,68,76]. All these approaches are centered on the concept of protein identification by mass spectrometry (MS), which is based on the acquisition of the mass of protein/peptide fragments, followed by alignment (through database search engines and algorithms) of the experimental data with protein sequences deposited in databases.…”

Section: Amyloidosis Typingmentioning

confidence: 99%

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Biochemical markers in early diagnosis and management of systemic amyloidoses

Lavatelli

Albertini

Fonzo

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Systemic amyloid diseases are characterized by widespread protein deposition as amyloid fibrils. Precise diagnostic framing is the prerequisite for a correct management of patients. This complex process is achieved through a series of steps, which include detection of the tissue amyloid deposits, identification of the amyloid type, demonstration of the amyloidogenic precursor, and evaluation of organ dysfunction/damage. Laboratory medicine plays a central role in the diagnosis and management of systemic amyloidoses, through the quantification of the amyloidogenic precursor and evaluation of end-organ damage using biomarkers.

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“…The application of proteomics seems to be a promising tool for reliable typing of amyloid. [35][36][37][38][39] These techniques, with high sensitivity and high specificity, are especially helpful to distinguish between AL and ATTR amyloid. One of these elegant techniques combines specific sampling by laser microdissection with the analytical power of proteomic analysis based on tandem mass spectrometry.…”

Section: Typing Of Amyloid With Confidencementioning

confidence: 99%