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Monoclonal Autoanti...
Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis
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- Khamis, Ramzi Y (author)
- Imperial College London
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- Hartley, Adam (author)
- Imperial College London
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- Caga-Anan, Mikhail (author)
- Imperial College London
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- Pandey, Samata S (author)
- Imperial College London
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- Marceddu, Cinzia (author)
- Imperial College London
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- Kojima, Chiari (author)
- Imperial College London
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- Chang, Shang-Hung (author)
- Imperial College London
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- Boyle, Joseph J (author)
- Imperial College London
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- Johnson, Jason L (author)
- University of Bristol
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- Björkbacka, Harry (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - cellulär metabolism och inflammation,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Cardiovascular Research - Cellular Metabolism and Inflammation
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- Guo, Liang (author)
- CVPath Institute INC
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- Finn, Aloke V (author)
- CVPath Institute INC
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- Virmani, Renu (author)
- CVPath Institute INC
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- Nilsson, Jan (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups
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- Haskard, Dorian O (author)
- Imperial College London
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: JACC: Cardiovascular Imaging. - : Elsevier BV. - 1876-7591 .- 1936-878X. ; 15:8, s. 1458-1470
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Abstract
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- BACKGROUND: Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.OBJECTIVES: The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.METHODS: The authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr -/-) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization. RESULTS: LO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr -/- mice, in the vicinity of macrophages. CONCLUSIONS: The authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Animals
- Antibodies, Monoclonal
- Atherosclerosis/metabolism
- Autoantibodies/chemistry
- Epitopes
- Humans
- Immunoglobulin G
- Lipoproteins, LDL/chemistry
- Mice
- Molecular Imaging
- Predictive Value of Tests
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Khamis, Ramzi Y
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Hartley, Adam
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Caga-Anan, Mikha ...
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Pandey, Samata S
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Marceddu, Cinzia
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Kojima, Chiari
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show more...
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Chang, Shang-Hun ...
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Boyle, Joseph J
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Johnson, Jason L
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Björkbacka, Harr ...
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Guo, Liang
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Finn, Aloke V
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Virmani, Renu
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Nilsson, Jan
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Haskard, Dorian ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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JACC: Cardiovasc ...
- By the university
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Lund University