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Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease

In light chain (LC) diseases, monoclonal immunoglobulin LCs are abundantly produced with the consequence in some cases to form deposits of a fibrillar or amorphous nature affecting various organs, such as heart and kidney. The factors that determine the solubility of any given LC in vivo are still n...

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Autores principales: Sternke-Hoffmann, Rebecca, Boquoi, Amelie, Lopez Y. Niedenhoff, David, Platten, Florian, Fenk, Roland, Haas, Rainer, Buell, Alexander K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083161/
https://www.ncbi.nlm.nih.gov/pubmed/32211238
http://dx.doi.org/10.7717/peerj.8771
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author Sternke-Hoffmann, Rebecca
Boquoi, Amelie
Lopez Y. Niedenhoff, David
Platten, Florian
Fenk, Roland
Haas, Rainer
Buell, Alexander K.
author_facet Sternke-Hoffmann, Rebecca
Boquoi, Amelie
Lopez Y. Niedenhoff, David
Platten, Florian
Fenk, Roland
Haas, Rainer
Buell, Alexander K.
author_sort Sternke-Hoffmann, Rebecca
collection PubMed
description In light chain (LC) diseases, monoclonal immunoglobulin LCs are abundantly produced with the consequence in some cases to form deposits of a fibrillar or amorphous nature affecting various organs, such as heart and kidney. The factors that determine the solubility of any given LC in vivo are still not well understood. We hypothesize that some of the biochemical properties of the LCs that have been shown to correlate with amyloid fibril formation in patients also can be used as predictors for the degree of kidney damage in a patient group that is only biased by protein availability. We performed detailed biochemical and biophysical investigations of light chains extracted and purified from the urine of a group of 20 patients with light chain disease. For all samples that contained a sufficiently high concentration of LC, we quantified the unfolding temperature of the LCs, the monomer-dimer distribution, the digestibility by trypsin and the formation of amyloid fibrils under various conditions of pH and reducing agent. We correlated the results of our biophysical and biochemical experiments with the degree of kidney damage in the patient group and found that most of these parameters do not correlate with kidney damage as defined by clinical parameters. However, the patients with the greatest impairment of kidney function have light chains which display very poor digestibility by trypsin. Most of the LC properties reported before to be predictors of amyloid formation cannot be used to assess the degree of kidney damage. Our finding that poor trypsin digestibility correlates with kidney damage warrants further investigation in order to probe a putative mechanistic link between these factors.
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spelling pubmed-70831612020-03-24 Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease Sternke-Hoffmann, Rebecca Boquoi, Amelie Lopez Y. Niedenhoff, David Platten, Florian Fenk, Roland Haas, Rainer Buell, Alexander K. PeerJ Biochemistry In light chain (LC) diseases, monoclonal immunoglobulin LCs are abundantly produced with the consequence in some cases to form deposits of a fibrillar or amorphous nature affecting various organs, such as heart and kidney. The factors that determine the solubility of any given LC in vivo are still not well understood. We hypothesize that some of the biochemical properties of the LCs that have been shown to correlate with amyloid fibril formation in patients also can be used as predictors for the degree of kidney damage in a patient group that is only biased by protein availability. We performed detailed biochemical and biophysical investigations of light chains extracted and purified from the urine of a group of 20 patients with light chain disease. For all samples that contained a sufficiently high concentration of LC, we quantified the unfolding temperature of the LCs, the monomer-dimer distribution, the digestibility by trypsin and the formation of amyloid fibrils under various conditions of pH and reducing agent. We correlated the results of our biophysical and biochemical experiments with the degree of kidney damage in the patient group and found that most of these parameters do not correlate with kidney damage as defined by clinical parameters. However, the patients with the greatest impairment of kidney function have light chains which display very poor digestibility by trypsin. Most of the LC properties reported before to be predictors of amyloid formation cannot be used to assess the degree of kidney damage. Our finding that poor trypsin digestibility correlates with kidney damage warrants further investigation in order to probe a putative mechanistic link between these factors. PeerJ Inc. 2020-03-17 /pmc/articles/PMC7083161/ /pubmed/32211238 http://dx.doi.org/10.7717/peerj.8771 Text en ©2020 Sternke-Hoffmann et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Sternke-Hoffmann, Rebecca
Boquoi, Amelie
Lopez Y. Niedenhoff, David
Platten, Florian
Fenk, Roland
Haas, Rainer
Buell, Alexander K.
Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease
title Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease
title_full Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease
title_fullStr Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease
title_full_unstemmed Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease
title_short Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease
title_sort biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083161/
https://www.ncbi.nlm.nih.gov/pubmed/32211238
http://dx.doi.org/10.7717/peerj.8771
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