Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis
Khamis, Ramzi Y ; Hartley, Adam ; Caga-Anan, Mikhail ; Pandey, Samata S ; Marceddu, Cinzia ; Kojima, Chiari ; Chang, Shang-Hung ; Boyle, Joseph J ; Johnson, Jason L and Björkbacka, Harry LU
, et al.
(2022)
In JACC: Cardiovascular Imaging
15(8).
p.1458-1470
- Abstract
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... (More)
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.
(Less)
- author
- Khamis, Ramzi Y
; Hartley, Adam
; Caga-Anan, Mikhail
; Pandey, Samata S
; Marceddu, Cinzia
; Kojima, Chiari
; Chang, Shang-Hung
; Boyle, Joseph J
; Johnson, Jason L
and Björkbacka, Harry
LU
, et al. (More)
- Khamis, Ramzi Y
; Hartley, Adam
; Caga-Anan, Mikhail
; Pandey, Samata S
; Marceddu, Cinzia
; Kojima, Chiari
; Chang, Shang-Hung
; Boyle, Joseph J
; Johnson, Jason L
; Björkbacka, Harry
LU
; Guo, Liang
; Finn, Aloke V
; Virmani, Renu
; Nilsson, Jan
LU
and Haskard, Dorian O
(Less)
- organization
- publishing date
- 2022-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Antibodies, Monoclonal, Atherosclerosis/metabolism, Autoantibodies/chemistry, Epitopes, Humans, Immunoglobulin G, Lipoproteins, LDL/chemistry, Mice, Molecular Imaging, Predictive Value of Tests
- in
- JACC: Cardiovascular Imaging
- volume
- 15
- issue
- 8
- pages
- 1458 - 1470
- publisher
- Elsevier
- external identifiers
-
- pmid:35926905
- scopus:85135426844
- ISSN
- 1876-7591
- DOI
- 10.1016/j.jcmg.2022.02.023
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
- id
- 0c448fbf-8fec-464a-a7ce-11c876ae45d8
- date added to LUP
- 2022-10-20 17:41:20
- date last changed
- 2024-04-18 15:05:32
@article{0c448fbf-8fec-464a-a7ce-11c876ae45d8,
abstract = {{<p>BACKGROUND: Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.</p><p>OBJECTIVES: The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.</p><p>METHODS: The authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr<br>
-/-) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.<br>
</p><p>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<br>
-/- mice, in the vicinity of macrophages.<br>
</p><p>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.</p>}},
author = {{Khamis, Ramzi Y and Hartley, Adam and Caga-Anan, Mikhail and Pandey, Samata S and Marceddu, Cinzia and Kojima, Chiari and Chang, Shang-Hung and Boyle, Joseph J and Johnson, Jason L and Björkbacka, Harry and Guo, Liang and Finn, Aloke V and Virmani, Renu and Nilsson, Jan and Haskard, Dorian O}},
issn = {{1876-7591}},
keywords = {{Animals; Antibodies, Monoclonal; Atherosclerosis/metabolism; Autoantibodies/chemistry; Epitopes; Humans; Immunoglobulin G; Lipoproteins, LDL/chemistry; Mice; Molecular Imaging; Predictive Value of Tests}},
language = {{eng}},
number = {{8}},
pages = {{1458--1470}},
publisher = {{Elsevier}},
series = {{JACC: Cardiovascular Imaging}},
title = {{Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis}},
url = {{http://dx.doi.org/10.1016/j.jcmg.2022.02.023}},
doi = {{10.1016/j.jcmg.2022.02.023}},
volume = {{15}},
year = {{2022}},
}