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Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatmen...

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Autores principales: Poshusta, Tanya L., Katoh, Nagaaki, Gertz, Morie A., Dispenzieri, Angela, Ramirez-Alvarado, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856080/
https://www.ncbi.nlm.nih.gov/pubmed/24248061
http://dx.doi.org/10.3390/ijms141122604
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author Poshusta, Tanya L.
Katoh, Nagaaki
Gertz, Morie A.
Dispenzieri, Angela
Ramirez-Alvarado, Marina
author_facet Poshusta, Tanya L.
Katoh, Nagaaki
Gertz, Morie A.
Dispenzieri, Angela
Ramirez-Alvarado, Marina
author_sort Poshusta, Tanya L.
collection PubMed
description Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR) do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.
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spelling pubmed-38560802013-12-09 Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis Poshusta, Tanya L. Katoh, Nagaaki Gertz, Morie A. Dispenzieri, Angela Ramirez-Alvarado, Marina Int J Mol Sci Article Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR) do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis. Molecular Diversity Preservation International (MDPI) 2013-11-15 /pmc/articles/PMC3856080/ /pubmed/24248061 http://dx.doi.org/10.3390/ijms141122604 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Poshusta, Tanya L.
Katoh, Nagaaki
Gertz, Morie A.
Dispenzieri, Angela
Ramirez-Alvarado, Marina
Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis
title Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis
title_full Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis
title_fullStr Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis
title_full_unstemmed Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis
title_short Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis
title_sort thermal stability threshold for amyloid formation in light chain amyloidosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856080/
https://www.ncbi.nlm.nih.gov/pubmed/24248061
http://dx.doi.org/10.3390/ijms141122604
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