Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an inherited disease, where the study of family history holds importance. This study evaluates the changes of age-of-onset (AOO) and other age-related clinical factors within and among families affected by ATTRv amyloidosis. ⋯ This study reveals that there has been a shift in patient profile, with a recent increase in male elderly cases, especially regarding probands. It shows that symptomatic patients exhibit less variability towards siblings, when compared to other family members, namely the transmitting ancestors' age of onset. This can influence genetic counselling guidelines.
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Early identification of immunoglobulin light-chain amyloidosis (AL) is crucial due to its rapid progression. Monoclonal light-chain (M-LC) testing is the first step in the diagnostic workup for patients with suspected cardiac amyloidosis (CA). We aimed to determine whether the time interval between the first CA suspicion and M-LC testing can be related to AL amyloidosis survival outcomes. ⋯ Monoclonal protein testing should be the first-step in the diagnostic workup for patients with echocardiographic/other instrumental red flags raising CA suspicion.
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Genotyping and amyloid fibril detection in tissues are generally considered the diagnostic gold standard in transthyretin-related amyloidosis. Patients carry less stable TTR homotetramers prone to dissociation into non-native monomers, which rapidly self-assemble into oligomers and, ultimately, amyloid fibrils. Thus, the initial event of the amyloid cascade produces the smallest transthyretin species: the monomers. This creates engineering opportunities for diagnosis that remain unexplored. ⋯ Monomeric TTR can function as a biomarker for evaluating disease progression and assessing responses to therapies targeted at stabilising native TTR.
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Numerous studies suggest a progressive accumulation of post-translationally modified peptides within amyloid fibrils, including isoaspartate (isoD) modifications. Here, we generated and characterised novel monoclonal antibodies targeting isoD-modified transthyretin (TTR). The antibodies were used to investigate the presence of isoD-modified TTR in deposits from transthyretin amyloidosis patients and to mediate antibody-dependent phagocytosis of TTR fibrils. ⋯ These antibodies label aged, non-native TTR deposits, leaving native TTR unattended and thereby potentially enabling new therapeutic approaches.