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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2011
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.
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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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