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Renal Expression of Light Chain Binding Proteins

Overproduction of human light chains (LCs) and immunoglobulins can result in various forms of renal disease such as cast nephropathy, monoclonal immunoglobulin deposition disease, LC proximal tubulopathy, AL amyloidosis, and crystal storing histiocytosis. This is caused by cellular uptake of LCs and...

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Autores principales: Reiter, Thomas, Pajenda, Sahra, O'Connell, David, Lynch, Ciara, Kapps, Sebastian, Agis, Hermine, Schmidt, Alice, Wagner, Ludwig, Leung, Nelson, Winnicki, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838590/
https://www.ncbi.nlm.nih.gov/pubmed/33521021
http://dx.doi.org/10.3389/fmed.2020.609582
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author Reiter, Thomas
Pajenda, Sahra
O'Connell, David
Lynch, Ciara
Kapps, Sebastian
Agis, Hermine
Schmidt, Alice
Wagner, Ludwig
Leung, Nelson
Winnicki, Wolfgang
author_facet Reiter, Thomas
Pajenda, Sahra
O'Connell, David
Lynch, Ciara
Kapps, Sebastian
Agis, Hermine
Schmidt, Alice
Wagner, Ludwig
Leung, Nelson
Winnicki, Wolfgang
author_sort Reiter, Thomas
collection PubMed
description Overproduction of human light chains (LCs) and immunoglobulins can result in various forms of renal disease such as cast nephropathy, monoclonal immunoglobulin deposition disease, LC proximal tubulopathy, AL amyloidosis, and crystal storing histiocytosis. This is caused by cellular uptake of LCs and overwhelmed intracellular transport and degradation in patients with high urine LC concentrations. LC kappa and lambda purification was evaluated by sodium dodecyl sulfate gel electrophoresis. LC and myeloma protein binding to immobilized renal proteins was measured by enzyme-linked immunosorbent assay (ELISA). The human protein microarray (HuProt™) was screened with purified kappa and lambda LC. Identified LC partners were subsequently analyzed in silico for renal expression sites using protein databases, Human Protein Atlas, UniProt, and Bgee. Binding of urinary LCs and immunoglobulins to immobilized whole renal proteins from 22 patients with myeloma or plasma cell dyscrasia was shown by ELISA. Forty lambda and 23 kappa interaction partners were identified from HuProt™ array screens, of which 21 were shared interactors. Among the total of 42 interactors, 12 represented cell surface proteins. Lambda binding signals were approximately 40% higher than kappa signals. LC interaction with renal cells and disease-causing pathologies are more complex than previously thought. It involves an extended spectrum of proteins expressed throughout the nephron, and their identification has been enabled by recently developed methods of protein analysis such as protein microarray screening. Further biochemical studies on interacting proteins are warranted to elucidate their clinical relevance.
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spelling pubmed-78385902021-01-28 Renal Expression of Light Chain Binding Proteins Reiter, Thomas Pajenda, Sahra O'Connell, David Lynch, Ciara Kapps, Sebastian Agis, Hermine Schmidt, Alice Wagner, Ludwig Leung, Nelson Winnicki, Wolfgang Front Med (Lausanne) Medicine Overproduction of human light chains (LCs) and immunoglobulins can result in various forms of renal disease such as cast nephropathy, monoclonal immunoglobulin deposition disease, LC proximal tubulopathy, AL amyloidosis, and crystal storing histiocytosis. This is caused by cellular uptake of LCs and overwhelmed intracellular transport and degradation in patients with high urine LC concentrations. LC kappa and lambda purification was evaluated by sodium dodecyl sulfate gel electrophoresis. LC and myeloma protein binding to immobilized renal proteins was measured by enzyme-linked immunosorbent assay (ELISA). The human protein microarray (HuProt™) was screened with purified kappa and lambda LC. Identified LC partners were subsequently analyzed in silico for renal expression sites using protein databases, Human Protein Atlas, UniProt, and Bgee. Binding of urinary LCs and immunoglobulins to immobilized whole renal proteins from 22 patients with myeloma or plasma cell dyscrasia was shown by ELISA. Forty lambda and 23 kappa interaction partners were identified from HuProt™ array screens, of which 21 were shared interactors. Among the total of 42 interactors, 12 represented cell surface proteins. Lambda binding signals were approximately 40% higher than kappa signals. LC interaction with renal cells and disease-causing pathologies are more complex than previously thought. It involves an extended spectrum of proteins expressed throughout the nephron, and their identification has been enabled by recently developed methods of protein analysis such as protein microarray screening. Further biochemical studies on interacting proteins are warranted to elucidate their clinical relevance. Frontiers Media S.A. 2021-01-13 /pmc/articles/PMC7838590/ /pubmed/33521021 http://dx.doi.org/10.3389/fmed.2020.609582 Text en Copyright © 2021 Reiter, Pajenda, O'Connell, Lynch, Kapps, Agis, Schmidt, Wagner, Leung and Winnicki. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Reiter, Thomas
Pajenda, Sahra
O'Connell, David
Lynch, Ciara
Kapps, Sebastian
Agis, Hermine
Schmidt, Alice
Wagner, Ludwig
Leung, Nelson
Winnicki, Wolfgang
Renal Expression of Light Chain Binding Proteins
title Renal Expression of Light Chain Binding Proteins
title_full Renal Expression of Light Chain Binding Proteins
title_fullStr Renal Expression of Light Chain Binding Proteins
title_full_unstemmed Renal Expression of Light Chain Binding Proteins
title_short Renal Expression of Light Chain Binding Proteins
title_sort renal expression of light chain binding proteins
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838590/
https://www.ncbi.nlm.nih.gov/pubmed/33521021
http://dx.doi.org/10.3389/fmed.2020.609582
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