Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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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. ⋯ Cardiac amyloidosis can be successfully subtyped without the prior enrichment of amyloid deposits with laser microdissection.
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Assess how baseline polyneuropathy severity impacts response to patisiran regarding neurologic impairment and quality of life (QOL) in patients with hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis). ⋯ Patisiran treatment improved neurologic function and QOL across a wide range of baseline polyneuropathy severities versus placebo. Timing of treatment initiation in patients with ATTRv amyloidosis remains critical for the preservation of function.(ClinicalTrials.gov number, NCT01960348).
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Biochemical characterisation of transthyretin variant TTR Y78F showed that this variant adopts a tetrameric conformation as normal TTR but exhibits some of the characteristics of an intermediate structure in the fibrillogenesis pathway. It was hypothesised that native Y78F might represent an early event in TTR amyloidogenesis. We immunised TTR knock out mice with recombinant variant TTR Y78F. ⋯ At the same time, this clone was negative for TTR V30M, soluble wild type protein or TTR T119M. The reactivity increased with oligomer formation and decreased as mature fibrils grow. After size exclusion chromatography (SEC) followed by sandwich ELISA and native immunoblotting, the mAb recognised two peaks (i) peak 1 present in acidified and in soluble variant proteins preparations with material above 146 KDa (ii) peak 2 only present in soluble L55P and S52P TTR preparations with material between 66 and 146 KDa. mAb CE11 may be a potential tool to survey therapeutical agents against TTR aggregation.
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Case Reports
A novel substitution of proline (P32L) destabilises β2-microglobulin inducing hereditary systemic amyloidosis.
β2-microglobulin amyloidosis was first described in the 1980s as a protein deposition disease associated with long-term haemodialysis. More recently, two inherited forms resulting from separate point mutations in the β2-microglobulin gene have been identified. In this report, we detail a novel β2M variant, P32L, caused by a unique dinucleotide mutation that is linked to systemic hereditary β2-microglobulin amyloidosis. ⋯ This work provides both clinical and experimental evidence supporting the critical role of P32 residue replacement in β2M amyloid fibrillogenesis.
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In the present study, it was investigated whether autonomic dysfunction could predict prognosis in light-chain (AL) amyloidosis patients. ⋯ The results of this study indicate that GAF on the AFT is an independent adverse prognostic factor for survival in AL amyloidosis patients.