Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Induction therapy is recommended before autologous stem cell transplantation (ASCT) for AL amyloidosis patients with high disease burden [bone marrow plasma cells (BMPCs) > 10%], but the role of induction therapy before ASCT in patients with low disease burden (BMPCs ≤ 10%) is still unknown. ⋯ Our study demonstrated that low disease burden AL patients who are eligible for ASCT may benefit from bortezomib-based induction therapy.
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Amyloidosis is a protein-misfolding disease characterised by insoluble amyloid deposits in the extracellular space of various organs and tissues, such as the brain, heart, kidneys, and ligaments. We previously reported the frequent occurrence of amyloid deposits in the ligament flavum in the presence of lumbar spinal canal stenosis (LSCS), which is a common spinal disorder in older individuals. Our earlier clinicopathological studies revealed that amyloid deposits derived from transthyretin (TTR) were involved in the pathogenesis of LSCS. ⋯ Biochemical studies revealed that the amyloid deposits consisted mainly of full-length ApoAI. As a notable finding, the lumbar ligamentum flavum of patients who had LSCS with double-positive amyloid deposits-positive for both ATTR and AApoAI-was significantly thicker than that of patients who had LSCS with single-positive-that is, positive for either ATTR or AApoAI-amyloid deposits. We thus suggest that lumbar AApoAI amyloid formation may enhance the pathological changes of lumbar ATTR amyloidosis in patients with LSCS.
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To investigate the clinicopathological features of sporadic amyloid transthyretin (ATTR) amyloidosis. ⋯ Sporadic ATTR amyloidosis patients might already be susceptible to a risk for sudden death even from an early-phase. Also, ATTR amyloid deposition in such cases might progress with a certain degree of regularity.
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V30M in transthyretin (TTR) gene is causative for hereditary ATTRv amyloidosis (familial amyloid polyneuropathy). ATTRv amyloidosis shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We aim at identifying genetic modifiers of disease onset that may contribute to this variability in Portuguese patients by identifying other variants in TTR locus, beyond the ATTRv amyloidosis causing variant that could play a regulatory role in its expression level. ⋯ Variants within the promoter region may modify disease expressivity and variants in the 3'UTR can impact the efficacy of novel therapeutic interventions. Importantly, the putative mechanisms of regulation of gene expression within the TTR gene deserve to be better explored, in order to be used in the future as potential therapeutical targets.
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Early events in immunoglobulin light chain (AL) amyloid formation are especially important as some early intermediates formed during the aggregation reaction are cytotoxic and play a critical role in the initiation of amyloid assembly. We investigated the early events in in vitro aggregation of cardiac amyloidosis AL proteins at pH 7.4. In this study we make distinctions between general aggregation and amyloid formation. ⋯ These dissociated species could play a key role in the already complex pathophysiology of AL amyloidosis. The degree of dissociation is inversely proportional to the amyloid yield. Our results highlight the importance and physiological consequences of intermediates/fibril dissociation in AL amyloidosis.