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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00032/full |
| _version_ | 1818676889045172224 |
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| author | Jonathan S Wall Stephen J Kennel Tina eRichey Amy eAllen Alan eStuckey Deborah T Weiss Sallie D Macy Robin eBarbour Peter eSeubert Alan eSolomon Dale eSchenk |
| author_facet | Jonathan S Wall Stephen J Kennel Tina eRichey Amy eAllen Alan eStuckey Deborah T Weiss Sallie D Macy Robin eBarbour Peter eSeubert Alan eSolomon Dale eSchenk |
| author_sort | Jonathan S Wall |
| collection | DOAJ |
| 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 microSPECT 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. |
| first_indexed | 2024-12-17T08:50:38Z |
| format | Article |
| id | doaj.art-7cfe2d04166f4f87bcc8dde5821b273f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T08:50:38Z |
| publishDate | 2011-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7cfe2d04166f4f87bcc8dde5821b273f2022-12-21T21:56:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242011-08-01210.3389/fimmu.2011.0003211320Generation and characterization of anti-AA amyloid-specific monoclonal antibodiesJonathan S Wall0Stephen J Kennel1Tina eRichey2Amy eAllen3Alan eStuckey4Deborah T Weiss5Sallie D Macy6Robin eBarbour7Peter eSeubert8Alan eSolomon9Dale eSchenk10University of Tennessee Graduate School of MedicineUniversity of Tennessee Graduate School of MedicineUniversity of Tennessee Graduate School of MedicineUniversity of Tennessee Graduate School of MedicineUniversity of Tennessee Graduate School of MedicineUniversity of Tennessee Graduate School of MedicineUniversity of Tennessee Graduate School of MedicineElan PharmaceuticalsElan PharmaceuticalsUniversity of Tennessee Graduate School of MedicineElan PharmaceuticalsAA 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 microSPECT 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00032/fullImmunotherapymonoclonal antibodiesAA amyloidosisradioimmunoimaging |
| spellingShingle | Jonathan S Wall Stephen J Kennel Tina eRichey Amy eAllen Alan eStuckey Deborah T Weiss Sallie D Macy Robin eBarbour Peter eSeubert Alan eSolomon Dale eSchenk Generation and characterization of anti-AA amyloid-specific monoclonal antibodies Frontiers in Immunology Immunotherapy monoclonal antibodies AA amyloidosis radioimmunoimaging |
| 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 | Immunotherapy monoclonal antibodies AA amyloidosis radioimmunoimaging |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00032/full |
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