Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. ⋯ Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p = .02) and higher frequency of renal response (100% vs. 68%; p = .005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.
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The novel class of compounds represented by lipid nanoparticle (LNP)-encapsulated siRNA formulations has an enormous potential to target disease, notably of the liver. Endocytosis of LNPs is believed to be mediated by APOE, an important serum protein of lipoprotein homeostasis. APOE polymorphisms affect binding to hepatic receptors and have been associated with development of specific disease. ⋯ Analysis of APOE polymorphisms in ATTR amyloidosis patients revealed three most frequent genotypes E3/3, E3/4 and E3/2. APOE stratification of patients did not show significant differences of TTR plasma concentrations following treatment. Our results suggest that APOE is an important mediator of TTR silencing by Patisiran, however efficacy is independent of the APOE genotype.
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Amyloidosis is an extremely rare event in rats. In this study, we report that lipopolysaccharide binding protein (LBP) is the most likely amyloidogenic protein in rat mammary amyloidosis. Histologically, corpora amylacea (CA) and stromal amyloid (SA) were observed in rat mammary glands, and needle-shaped amyloid (NA) was also observed on the surface or gap of CA and SA. ⋯ In the same analysis, LBP was detected as a prime candidate protein in NA, and NA was positive following immunohistochemistry and immunoelectron microscopy with anti-LBP antibody. Furthermore, synthetic peptides derived from rat LBP formed amyloid fibrils in vitro. Overall, these results provide evidence that LBP is an amyloid precursor protein of NA in rat mammary glands.
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Background: Tafamidis is approved in over 40 countries to delay neurologic progression in patients with transthyretin amyloid polyneuropathy (ATTR-PN). A comprehensive, integrated analysis of safety data from interventional, observational and surveillance studies of tafamidis in ATTR-PN patients was conducted. Methods: Safety data from all sponsored, completed, or ongoing, Phase 2/3 studies of tafamidis in ATTR-PN patients as of 3 January 2017 were pooled. ⋯ Post-marketing surveillance reports generally reflected the known safety profile of tafamidis. Conclusions: This analysis did not reveal any significant new safety findings; tafamidis was generally safe and well tolerated in ATTR-PN patients. ClinicalTrials.gov: NCT00409175, NCT00791492, NCT00630864, NCT01435655, NCT00925002, and NCT00628745.
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Background: Localized nodular deposits of AL amyloid are seen in different tissues/organs; however, the pathogenesis of this form of amyloidosis remains unclear. Recently, Sjögren syndrome combined with localized nodular AL amyloidosis has been noted. Here, we report Sjögren syndrome cases showing multifocal nodular AL amyloidosis and the followed benign course. ⋯ In two cases amyloid deposition was found on gastric mucosa. Two cases received small doses of oral prednisone, with no further appearance of amyloidoma. Conclusion: Sjögren syndrome-related plasma cell disorder may be responsible for the formation of this unique multifocal nodular AL amyloidosis.