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Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies
AA amyloidosis results from the pathologic deposition in the kidneys and other organs of fibrils composed of N-terminal fragments of serum amyloid A protein (SAA). Given that there are only limited means to visualize these deposits, we have developed a series of mAbs, 2A4, 7D8, and 8G9, that bind sp...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341974/ https://www.ncbi.nlm.nih.gov/pubmed/22566822 http://dx.doi.org/10.3389/fimmu.2011.00032 |
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author | Wall, Jonathan S. Kennel, Stephen J. Richey, Tina Allen, Amy Stuckey, Alan Weiss, Deborah T. Macy, Sallie D. Barbour, Robin Seubert, Peter Solomon, Alan Schenk, Dale |
author_facet | Wall, Jonathan S. Kennel, Stephen J. Richey, Tina Allen, Amy Stuckey, Alan Weiss, Deborah T. Macy, Sallie D. Barbour, Robin Seubert, Peter Solomon, Alan Schenk, Dale |
author_sort | Wall, Jonathan S. |
collection | PubMed |
description | AA amyloidosis results from the pathologic deposition in the kidneys and other organs of fibrils composed of N-terminal fragments of serum amyloid A protein (SAA). Given that there are only limited means to visualize these deposits, we have developed a series of mAbs, 2A4, 7D8, and 8G9, that bind specifically with nanomolar affinity to a carboxy-terminal epitope generated following proteolysis of SAA that yields the predominant component of AA amyloid deposits. Notably, these antibodies do not recognize native SAA, they retain their immunoreactivity when radiolabeled with I-125 and, after injection into AA amyloidotic mice, localize, as evidenced by autoradiography and micro-single photon emission computed tomography imaging, to histologically confirmed areas of amyloid deposition; namely, spleen, liver, and pancreas. The results of our in vitro and in vivo studies demonstrate the AA fibril-selectivity of mAbs 2A4, 7D8, and 8G9 and warrant further investigation into their role as novel diagnostic agents for patients with AA amyloidosis. |
format | Online Article Text |
id | pubmed-3341974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33419742012-05-07 Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies Wall, Jonathan S. Kennel, Stephen J. Richey, Tina Allen, Amy Stuckey, Alan Weiss, Deborah T. Macy, Sallie D. Barbour, Robin Seubert, Peter Solomon, Alan Schenk, Dale Front Immunol Immunology AA amyloidosis results from the pathologic deposition in the kidneys and other organs of fibrils composed of N-terminal fragments of serum amyloid A protein (SAA). Given that there are only limited means to visualize these deposits, we have developed a series of mAbs, 2A4, 7D8, and 8G9, that bind specifically with nanomolar affinity to a carboxy-terminal epitope generated following proteolysis of SAA that yields the predominant component of AA amyloid deposits. Notably, these antibodies do not recognize native SAA, they retain their immunoreactivity when radiolabeled with I-125 and, after injection into AA amyloidotic mice, localize, as evidenced by autoradiography and micro-single photon emission computed tomography imaging, to histologically confirmed areas of amyloid deposition; namely, spleen, liver, and pancreas. The results of our in vitro and in vivo studies demonstrate the AA fibril-selectivity of mAbs 2A4, 7D8, and 8G9 and warrant further investigation into their role as novel diagnostic agents for patients with AA amyloidosis. Frontiers Research Foundation 2011-08-08 /pmc/articles/PMC3341974/ /pubmed/22566822 http://dx.doi.org/10.3389/fimmu.2011.00032 Text en Copyright © 2011 Wall, Kennel, Richey, Allen, Stuckey, Weiss, Macy, Barbour, Seubert, Solomon and Schenk. http://www.frontiersin.org/licenseagreement This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with. |
spellingShingle | Immunology Wall, Jonathan S. Kennel, Stephen J. Richey, Tina Allen, Amy Stuckey, Alan Weiss, Deborah T. Macy, Sallie D. Barbour, Robin Seubert, Peter Solomon, Alan Schenk, Dale Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies |
title | Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies |
title_full | Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies |
title_fullStr | Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies |
title_full_unstemmed | Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies |
title_short | Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies |
title_sort | generation and characterization of anti-aa amyloid-specific monoclonal antibodies |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341974/ https://www.ncbi.nlm.nih.gov/pubmed/22566822 http://dx.doi.org/10.3389/fimmu.2011.00032 |
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